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| Meta Title | Schizophrenia - Wikipedia |
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| Boilerpipe Text | Schizophrenia
Cloth
embroidered
by a person diagnosed with schizophrenia
Pronunciation
SKIT
-sə-
FREE
-nee-ə
,
SKIT
-sə-
FREN
-ee-ə
Specialty
Psychiatry
[
1
]
Symptoms
Hallucinations
,
delusions
,
disorganized thinking
or behavior,
flat
or
inappropriate affect
[
2
]
[
3
]
Complications
Harm to self or others,
social isolation
,
heart disease
,
suicide
,
lifestyle diseases
,
[
4
]
obesity
and
type 2 diabetes
arising from
antipsychotic
medication
[
5
]
[
6
]
Usual onset
Ages 16 to 30
[
3
]
Duration
Chronic
[
3
]
Causes
Environmental and genetic factors
[
7
]
Risk factors
Family history
,
cannabis
use in adolescence,
hallucinogen
- or
amphetamine
-associated psychosis,
[
8
]
problems during pregnancy,
childhood adversity
, being born or raised in a city
[
7
]
[
9
]
Diagnostic method
Based on observed behavior, reported experiences, and reports of others familiar with the person
[
10
]
Differential diagnosis
Substance use disorder
,
Huntington's disease
,
mood disorders
(
bipolar disorder
,
major depressive disorder
),
autism
,
[
11
]
borderline personality disorder
,
[
12
]
schizophreniform disorder
,
schizotypal personality disorder
,
schizoid personality disorder
,
antisocial personality disorder
,
psychotic depression
,
anxiety
,
disruptive mood dysregulation disorder
,
sleep paralysis
Management
Counseling,
life skills
training
[
2
]
[
7
]
Medication
Antipsychotics
[
7
]
Prognosis
20–28 years shorter
life expectancy
[
13
]
[
14
]
Frequency
~0.32% (1 in 300) of the global population is affected
[
15
]
Deaths
~17,000 (2015)
[
16
]
Schizophrenia
is a
mental disorder
[
17
]
[
7
]
characterized variously by
hallucinations
(typically,
hearing voices
),
delusions
,
disorganized thinking
or behavior,
[
10
]
and
flat
or
inappropriate affect
.
[
7
]
Symptoms
develop gradually
and typically begin during young adulthood and rarely resolve.
[
3
]
[
10
]
[
18
]
There is no objective diagnostic test; diagnosis is based on observed behavior, a
psychiatric history
that includes the person's reported experiences, and reports of others familiar with the person.
[
10
]
For a
formal diagnosis
, the described symptoms need to have been present for at least six months (according to the
DSM-5
) or one month (according to the
ICD-11
).
[
10
]
[
19
]
Many people with schizophrenia have other mental disorders, especially
mood
,
anxiety
, and
substance use
disorders, as well as
obsessive–compulsive disorder
(OCD).
[
10
]
The
lifetime prevalence
of developing schizophrenia is about 0.3% to 0.7%.
[
20
]
In 2017, there were an estimated 1.1 million new cases and in 2022 a total of 24 million cases globally.
[
2
]
[
21
]
Males are more often affected and on average have an earlier onset than females.
[
2
]
The causes of schizophrenia may include
genetic
and
environmental
factors.
[
7
]
Genetic factors include a variety of common and rare
genetic variants
.
[
22
]
Possible environmental factors include
being raised in a city
, childhood adversity,
cannabis
use during adolescence, infections, the
age of a person's mother
or
father
, and poor
nutrition during pregnancy
.
[
7
]
[
23
]
About half of those diagnosed with schizophrenia will experience a marked improvement over the long term with no further relapses, and a small proportion of these will recover completely.
[
10
]
[
24
]
The other half will have a lifelong impairment.
[
25
]
In severe cases, people may be admitted to hospitals.
[
24
]
Social problems such as
long-term unemployment
, poverty,
homelessness
, exploitation, and victimization are commonly correlated with schizophrenia.
[
26
]
[
27
]
Compared to the general population, people with schizophrenia have a higher suicide rate (about 5% overall) and more
physical health problems
,
[
28
]
[
29
]
leading to an average decrease in
life expectancy
by 20
[
13
]
to 28 years.
[
14
]
In 2015, an estimated 17,000 deaths were linked to schizophrenia.
[
16
]
The mainstay of treatment is
antipsychotic
medication, including
olanzapine
and
risperidone
, along with
counseling
, job training, and
social rehabilitation
.
[
7
]
Up to a third of people do not respond to initial antipsychotics, in which case
clozapine
is offered.
[
30
]
Most antipsychotics improve schizophrenia symptoms, with
clozapine
the most effective overall; side effects vary considerably and guide treatment choices.
[
31
]
In situations where doctors judge that there is a risk of harm to self or others, they may impose short
involuntary hospitalization
.
[
32
]
Long-term hospitalization is used on a small number of people with severe schizophrenia.
[
33
]
In some countries where supportive services are limited or unavailable, long-term hospital stays are more common.
[
34
]
Signs and symptoms
Schizophrenia is a
mental disorder
characterized by significant alterations in
perception
, thoughts, mood, and behavior.
[
35
]
Symptoms are described in terms of positive, negative, and cognitive symptoms.
[
3
]
[
36
]
The positive symptoms of schizophrenia are the same for any
psychosis
and are sometimes referred to as psychotic symptoms. These may be present in any of the different psychoses and are often transient, making early diagnosis of schizophrenia problematic. Psychosis noted for the first time in a person who is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP).
[
37
]
[
38
]
Positive symptoms
Example of delusional obsession with numbers, disorganized thoughts, occurring with paranoid schizophrenia.
Positive symptoms are those that are not normally experienced, but are present in people during a psychotic episode in schizophrenia, including
delusions
,
hallucinations
, and disorganized thoughts, speech and behavior or inappropriate affect, typically regarded as manifestations of psychosis.
[
37
]
Hallucinations occur at some point in the lifetimes of 80% of those with schizophrenia
[
39
]
and most commonly involve the sense of
hearing
(most often
hearing voices
), but can sometimes involve any of the other
senses
such as
taste
,
sight
,
smell
, and
touch
.
[
40
]
The frequency of hallucinations involving multiple senses is double the rate of those involving only one sense.
[
39
]
They are also typically related to the content of the delusional theme.
[
41
]
Delusions
are
bizarre
or
persecutory
in nature.
Distortions of self-experience
such as feeling that
others can hear one's thoughts
(thought broadcasting delusion) or that
thoughts are being inserted into one's mind
, sometimes termed passivity phenomena, are also common.
[
42
]
[
3
]
The type and content of auditory and visual hallucinations appears to be influenced, at least in part, by cultural and religious factors. Patients in the United Kingdom and United States are more likely to report hearing criticisms and commands; patients in Africa, Asia, and the Middle East report more religious messaging in their hallucinations. This is true even among transplants to these countries, suggesting these differences are cultural, and not genetic.
[
citation needed
]
Positive symptoms generally respond well to medication
[
7
]
and become reduced over the course of the illness, perhaps linked to the age-related decline in dopamine activity.
[
10
]
Negative symptoms
Negative symptoms are deficits of normal emotional responses, or of other thought processes. The five recognized domains of negative symptoms are:
blunted affect
– showing flat expressions (monotone) or little emotion;
alogia
– a poverty of speech;
anhedonia
– an inability to feel pleasure;
asociality
– the lack of desire to form relationships, and
avolition
– a lack of motivation and
apathy
.
[
43
]
[
44
]
Avolition and anhedonia are seen as motivational deficits resulting from impaired reward processing.
[
45
]
[
46
]
Reward is the main driver of motivation and this is mostly mediated by dopamine.
[
46
]
It has been suggested that negative symptoms are multidimensional and they have been categorised into two subdomains of apathy or lack of motivation, and diminished expression.
[
43
]
[
47
]
Apathy includes avolition, anhedonia, and social withdrawal; diminished expression includes blunt affect and alogia.
[
48
]
Sometimes diminished expression is treated as both verbal and non-verbal.
[
49
]
Apathy accounts for around 50% of the most often found negative symptoms and affects functional outcome and subsequent quality of life. Apathy is related to disrupted cognitive processing affecting memory and planning, including goal-directed behaviour.
[
50
]
The two subdomains have suggested a need for separate treatment approaches.
[
51
]
A lack of distress is another noted negative symptom.
[
52
]
A distinction is often made between those negative symptoms that are inherent to schizophrenia, termed primary; and those that result from positive symptoms, from the side effects of antipsychotics, substance use disorder, and social deprivation, termed secondary negative symptoms.
[
53
]
Negative symptoms are less responsive to medication and the most difficult to treat.
[
51
]
However, if properly assessed, secondary negative symptoms are amenable to treatment.
[
47
]
There is some evidence that the negative symptoms of schizophrenia are amenable to psychostimulant medication, although such drugs have varying degrees of risk for causing positive psychotic symptoms.
[
54
]
Scales for specifically assessing the presence of negative symptoms, and for measuring their severity, and their changes have been introduced since the earlier scales such as the
PANSS
that deals with all types of symptoms.
[
51
]
These scales are the
Clinical Assessment Interview for Negative Symptoms
(CAINS), and the
Brief Negative Symptom Scale
(BNSS) also known as second-generation scales.
[
51
]
[
52
]
[
55
]
In 2020, ten years after its introduction, a cross-cultural study of the use of BNSS found valid and reliable
psychometric
evidence for its five-domain structure cross-culturally. The BNSS can assess both the presence and severity of negative symptoms of the five recognized domains and an additional item of reduced normal distress. It has been used to measure changes in negative symptoms in trials of psychosocial and pharmacological interventions.
[
52
]
Cognitive symptoms
Map of deficits in
neural tissue
throughout the human brain in a patient with schizophrenia. The most deficient areas are magenta, while the least deficient areas are blue.
Diagram of the brain in schizophrenia
An estimated 70% of those with schizophrenia have cognitive deficits, and these are most pronounced in early-onset and late-onset illness.
[
56
]
[
57
]
These are often evident long before the onset of illness in the
prodromal stage
, and may be present in childhood or early adolescence.
[
58
]
[
59
]
They are core features but not considered core symptoms, as are positive and negative symptoms.
[
60
]
[
61
]
However, their presence and degree of dysfunction are taken as better indicators of functionality than the presentation of core symptoms.
[
58
]
Cognitive deficits become worse at first episode psychosis but then return to baseline, and remain fairly stable over the course of the illness.
[
62
]
[
63
]
Cognitive deficits may be of
neurocognition
(nonsocial) or of
social cognition
.
[
56
]
Neurocognition is the ability to receive and remember information, and includes verbal fluency,
memory
,
reasoning
,
problem solving
,
speed of processing
, and
auditory
and visual perception.
[
63
]
Verbal memory
and attention are seen to be the most affected.
[
64
]
[
65
]
Verbal memory impairment is associated with a decreased level of
semantic processing
(relating meaning to words).
[
66
]
Another memory impairment is that of
episodic memory
.
[
67
]
An impairment in visual perception that is consistently found in schizophrenia is that of
visual backward masking
.
[
63
]
Visual processing
impairments include an inability to perceive complex
visual illusions
.
[
68
]
Social cognition is concerned with the mental operations needed to interpret, and understand the self and others in the social world.
[
63
]
[
56
]
This is also an associated impairment, and
facial emotion perception
is often found to be difficult.
[
69
]
[
70
]
Cognitive impairments do not usually respond to antipsychotics, and there are a number of
interventions
that are used to try to improve them;
cognitive remediation therapy
is of particular help.
[
61
]
Neurological soft signs
of clumsiness and loss of fine motor movement are often found in schizophrenia, which may resolve with effective treatment of FEP.
[
19
]
[
71
]
Onset
Onset typically occurs between the late teens and early 30s, with the peak incidence occurring in males in the early to mid-twenties, and in females in the late twenties.
[
3
]
[
10
]
[
19
]
Onset before the age of 17 is known as early-onset,
[
72
]
and before the age of 13, as can sometimes occur, is known as
childhood schizophrenia
or very early-onset.
[
10
]
[
73
]
Onset can occur between the ages of 40 and 60, known as late-onset schizophrenia.
[
56
]
Onset over the age of 60, which may be difficult to differentiate as schizophrenia, is known as very-late-onset schizophrenia-like psychosis.
[
56
]
Late onset has shown that a higher rate of females are affected; they have less severe symptoms and need lower doses of antipsychotics.
[
56
]
The tendency for earlier onset in males is later seen to be balanced by a
post-menopausal
increase in the development in females.
Estrogen
produced pre-menopause has a dampening effect on dopamine receptors but its protection can be overridden by a genetic overload.
[
74
]
There has been a dramatic increase in the numbers of older adults with schizophrenia.
[
75
]
Onset may happen suddenly or may occur after the slow and gradual development of a number of signs and symptoms, a period known as the
prodromal stage
.
[
10
]
Up to 75% of those with schizophrenia go through a prodromal stage.
[
76
]
The negative and cognitive symptoms in the prodrome stage can precede FEP (first episode psychosis) by many months and up to five years.
[
62
]
[
77
]
The period from FEP and treatment is known as the duration of untreated psychosis (DUP) which is seen to be a factor in functional outcome. The prodromal stage is the high-risk stage for the development of psychosis.
[
63
]
Since the progression to first episode psychosis is not inevitable, an alternative term is often preferred of
at risk mental state
.
[
63
]
Cognitive dysfunction at an early age impacts a young person's usual cognitive development.
[
78
]
Recognition and early intervention at the prodromal stage would minimize the associated disruption to educational and social development and has been the focus of many studies.
[
62
]
[
77
]
Risk factors
Schizophrenia is described as a
neurodevelopmental disorder
with no precise boundary, or single cause, and is thought to develop from
gene–environment interactions
with involved vulnerability factors.
[
7
]
[
79
]
[
80
]
The interactions of these
risk factors
are complex, as numerous and diverse
insults
from conception to adulthood can be involved.
[
80
]
A genetic predisposition on its own, without interacting environmental factors, will not give rise to the development of schizophrenia.
[
80
]
[
81
]
The genetic component means that
prenatal
brain development is disturbed, and environmental influence affects the postnatal development of the brain.
[
82
]
Evidence suggests that genetically susceptible children are more likely to be vulnerable to the effects of environmental risk factors.
[
82
]
Genetic
Estimates of the
heritability
of schizophrenia are between 70% and 80%, which implies that 70% to 80% of the individual differences in risk of schizophrenia are associated with genetics.
[
22
]
[
83
]
These estimates vary because of the
difficulty in separating
genetic and environmental influences, and their accuracy has been queried.
[
84
]
[
85
]
The greatest risk factor for developing schizophrenia is having a
first-degree relative
with the disease (risk is 6.5%); more than 40% of
identical twins
of those with schizophrenia are also affected.
[
86
]
If one parent is affected the risk is about 13% and if both are affected the risk is nearly 50%.
[
83
]
However, the
DSM-5
indicates that most people with schizophrenia have no family history of psychosis.
[
10
]
Results of
candidate gene
studies of schizophrenia have generally failed to find consistent associations,
[
87
]
and the
genetic loci
identified by
genome-wide association studies
explain only a small fraction of the variation in the disease.
[
88
]
Many
genes
are known to be involved in schizophrenia, each with small effects and unknown
transmission
and
expression
.
[
22
]
[
89
]
[
90
]
The summation of these effect sizes into a
polygenic risk score
can explain at least 7% of the variability in liability for schizophrenia.
[
91
]
Around 5% of cases of schizophrenia are understood to be at least partially attributable to rare
copy number variations
(CNVs); these
structural variations
are associated with known genomic disorders involving
deletions
at
22q11.2
(
DiGeorge syndrome
) and
17q12
(
17q12 microdeletion syndrome
), duplications at
16p11.2
(most frequently found) and deletions at
15q11.2
(
Burnside–Butler syndrome
).
[
92
]
Some of these CNVs increase the risk of developing schizophrenia by as much as 20-fold, and are frequently comorbid with autism and intellectual disabilities.
[
92
]
The genes
CRHR1
and
CRHBP
are associated with the severity of suicidal behavior. These genes code for stress response proteins needed in the control of the
HPA axis
, and their interaction can affect this axis. Response to stress can cause lasting changes in the
function of the HPA axis
possibly disrupting the negative feedback mechanism,
homeostasis
, and the regulation of emotion leading to altered behaviors.
[
81
]
The question of how schizophrenia could be primarily genetically influenced, given that people with schizophrenia have lower fertility rates, is a paradox. It is expected that
genetic variants
that increase the risk of schizophrenia would be selected against, due to their negative effects on
reproductive fitness
. A number of potential explanations have been proposed, including that
alleles
associated with schizophrenia risk confers a fitness advantage in unaffected individuals.
[
93
]
[
94
]
While some evidence has not supported this idea,
[
85
]
others propose that a large number of alleles each contributing a small amount can persist.
[
95
]
A meta-analysis found that oxidative
DNA damage
was significantly increased in schizophrenia.
[
96
]
Environmental
Environmental factors, each associated with a slight risk of developing schizophrenia in later life include
oxygen deprivation
, infection,
prenatal maternal stress
, and malnutrition in the mother during prenatal development.
[
97
]
A risk is associated with maternal obesity, in increasing
oxidative stress
, and dysregulating the dopamine and serotonin pathways.
[
98
]
Both maternal stress and infection have been demonstrated to alter fetal
neurodevelopment
through an increase of pro-inflammatory
cytokines
.
[
99
]
There is a slighter risk associated with being born in the winter or spring possibly due to
vitamin D deficiency
[
100
]
or a prenatal
viral infection
.
[
86
]
Other infections during pregnancy or around the time of birth that have been linked to an increased risk include infections by
Toxoplasma gondii
and
Chlamydia
.
[
101
]
The increased risk is about five to eight percent.
[
102
]
Viral infections of the brain during childhood are also linked to a risk of schizophrenia during adulthood.
[
103
]
Cat exposure
is also associated with an increased risk of broadly defined schizophrenia-related disorders, with an
odds ratio
of 2.4.
[
104
]
Exposure to specific medications such as
tramadol
and
desmopressin
has been found be associated with an increased risk of incident schizophrenia, while other medications including
anti-protozoans
were associated with a decrease in schizophrenia risk.
[
105
]
Adverse childhood experiences
(ACEs), severe forms of which are classed as
childhood trauma
, range from being bullied or abused, to the death of a parent.
[
106
]
Many adverse childhood experiences can cause
toxic stress
and increase the risk of psychosis.
[
106
]
[
107
]
[
108
]
Chronic trauma, including ACEs, can promote lasting inflammatory dysregulation throughout the nervous system.
[
109
]
It is suggested that early stress may contribute to the development of schizophrenia through these alterations in the immune system.
[
109
]
Schizophrenia was the last diagnosis to benefit from the link made between ACEs and adult mental health outcomes.
[
110
]
Living in an
urban environment
during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two,
[
28
]
[
111
]
even after taking into account
drug use
,
ethnic group
, and size of
social group
.
[
112
]
A possible link between the
urban environment and pollution
has been suggested to be the cause of the elevated risk of schizophrenia.
[
113
]
Other risk factors include
social isolation
, immigration related to social adversity and racial discrimination, family dysfunction, unemployment, and poor housing conditions.
[
86
]
[
114
]
[
115
]
Having a
father older than 40 years
, or parents younger than 20 years are also associated with schizophrenia.
[
7
]
[
116
]
Substance use
About half of those with schizophrenia use
recreational drugs
including
alcohol
, tobacco, and
cannabis
excessively.
[
117
]
[
118
]
Use of
stimulants
such as
amphetamine
and
cocaine
can lead to a temporary
stimulant psychosis
, which presents very similarly to schizophrenia.
[
119
]
Rarely, alcohol use can also result in a similar
alcohol-related psychosis
.
[
86
]
[
120
]
Drugs may also be used as coping mechanisms by people who have schizophrenia, to deal with depression,
anxiety
, boredom, and
loneliness
.
[
117
]
[
121
]
The use of cannabis and tobacco are not associated with the development of cognitive deficits, and sometimes a reverse relationship is found where their use improves these symptoms.
[
61
]
However,
substance use disorders
are associated with an increased risk of suicide, and a poor response to treatment.
[
122
]
[
123
]
Cannabis use
may be a contributory factor in the development of schizophrenia, potentially increasing the risk of the disease in those who are already at risk.
[
124
]
[
125
]
[
126
]
The increased risk may require the presence of certain genes within an individual.
[
23
]
Its use is associated with doubling the rate.
[
127
]
Causes
The causes of schizophrenia are still unknown. Several models have been put forward to explain the link between altered brain function and schizophrenia.
[
28
]
The prevailing model of schizophrenia is that of a
neurodevelopmental disorder
, and the underlying changes that occur before symptoms become evident are seen as arising from the
interaction between genes and the environment
.
[
128
]
Extensive studies support this model.
[
76
]
Maternal infections,
malnutrition
and
complications during pregnancy
and
childbirth
are known risk factors for the development of schizophrenia, which usually emerges between the ages of 18 and 25, a period that overlaps with certain stages of neurodevelopment.
[
129
]
Gene-environment interactions lead to deficits in the
neural circuitry
that affect sensory and cognitive functions.
[
76
]
The common dopamine and glutamate models proposed are not mutually exclusive; each is seen to have a role in the neurobiology of schizophrenia.
[
130
]
The most common model put forward was the
dopamine hypothesis of schizophrenia
, which attributes psychosis to the mind's faulty interpretation of the misfiring of
dopaminergic neurons
.
[
131
]
This has been directly related to the symptoms of delusions and hallucinations.
[
132
]
[
133
]
[
134
]
Abnormal dopamine signaling has been implicated in schizophrenia based on the usefulness of medications that affect the dopamine receptor and the observation that dopamine levels are increased during acute psychosis.
[
135
]
[
136
]
A decrease in
D
1
receptors
in the
dorsolateral prefrontal cortex
may also be responsible for deficits in
working memory
.
[
137
]
[
138
]
The
glutamate hypothesis of schizophrenia
links alterations between
glutamatergic neurotransmission
and the
neural oscillations
that affect
connections between the thalamus and the cortex
.
[
139
]
Studies have shown that a reduced expression of a
glutamate receptor
–
NMDA receptor
, and glutamate blocking drugs such as
phencyclidine
and
ketamine
can mimic the symptoms and cognitive problems associated with schizophrenia.
[
139
]
[
140
]
[
141
]
Post-mortem studies consistently find that a subset of these neurons fail to express
GAD67
(
GAD1
),
[
142
]
in addition to abnormalities in
brain morphometry
. The subsets of interneurons that are abnormal in schizophrenia are responsible for the synchronizing of neural ensembles needed during working memory tasks. These give the neural oscillations produced as
gamma waves
that have a frequency of between 30 and 80
hertz
. Both working memory tasks and gamma waves are impaired in schizophrenia, which may reflect abnormal interneuron functionality.
[
142
]
[
143
]
[
144
]
[
145
]
An important process that may be disrupted in neurodevelopment is astrogenesis – the formation of
astrocytes
. Astrocytes are crucial in contributing to the formation and maintenance of neural circuits and it is believed that disruption in this role can result in a number of neurodevelopmental disorders including schizophrenia.
[
146
]
Evidence suggests that reduced numbers of astrocytes in deeper cortical layers are assocociated with a diminished expression of
EAAT2
, a
glutamate transporter
in astrocytes; supporting the glutamate hypothesis.
[
146
]
Deficits in
executive functions
, such as
planning
,
inhibition
, and
working memory
, are pervasive in schizophrenia. Although these functions are separable, their dysfunction in schizophrenia may reflect an underlying deficit in the ability to represent goal related information in working memory, and to use this to direct cognition and behavior.
[
147
]
[
148
]
These impairments have been linked to a number of
neuroimaging
and
neuropathological abnormalities
. For example, functional neuroimaging studies report evidence of reduced neural processing efficiency, whereby the
dorsolateral prefrontal cortex
is activated to a greater degree to achieve a certain level of performance relative to controls on working memory tasks. These abnormalities may be linked to the consistent post-mortem finding of reduced
neuropil
, evidenced by increased
pyramidal cell
density and reduced
dendritic spine
density. These cellular and functional abnormalities may also be reflected in structural neuroimaging studies that find reduced
grey matter
volume in association with deficits in working memory tasks.
[
149
]
Positive symptoms have been linked to cortical thinning in the
superior temporal gyrus
.
[
150
]
The severity of negative symptoms has been linked to reduced thickness in the left medial
orbitofrontal cortex
.
[
151
]
Anhedonia, traditionally defined as a reduced capacity to experience
pleasure
, is frequently reported in schizophrenia. However, a large body of evidence suggests that
hedonic responses
are intact in schizophrenia,
[
152
]
and that what is reported to be
anhedonia
is a reflection of dysfunction in other processes related to reward.
[
153
]
Overall, a failure of reward prediction is thought to lead to impairment in the generation of cognition and behavior required to obtain rewards, despite normal hedonic responses.
[
154
]
Another theory links abnormal
brain lateralization
to the development of
being left-handed
which is significantly more common in those with schizophrenia.
[
155
]
This abnormal development of hemispheric asymmetry is noted in schizophrenia.
[
156
]
Studies have concluded that the link is a true and verifiable effect that may reflect a genetic link between lateralization and schizophrenia.
[
155
]
[
157
]
Bayesian models of brain functioning
have been used to link abnormalities in cellular functioning to symptoms.
[
158
]
[
159
]
Both hallucinations and delusions have been suggested to reflect improper encoding of
prior expectations
, thereby causing expectation to excessively influence sensory perception and the formation of beliefs. In approved models of
circuits
that mediate
predictive coding
, reduced NMDA receptor activation, could in theory result in the positive symptoms of delusions and hallucinations.
[
160
]
[
161
]
[
162
]
From an
evolutionary
perspective
, schizophrenia is regarded as an "evolutionary puzzle" because it shows high heritability (~60-80 %) and significant impairment in reproduction, yet persists at ~1 % prevalence. One hypothesis suggests that mild schizotypal traits may have historically conferred advantages (such as enhanced creativity or verbal ability,) while more severe forms represent the breakdown of these systems. Experimental models also propose that selection for language and social-cognitive complexity may have increased vulnerability to psychosis when environmental or developmental stressors intervene.
[
163
]
[
164
]
Diagnosis
Criteria
Schizophrenia is diagnosed based on criteria in either the
Diagnostic and Statistical Manual of Mental Disorders
(DSM) published by the
American Psychiatric Association
or the
International Statistical Classification of Diseases and Related Health Problems
(ICD) published by the
World Health Organization
(WHO). These criteria use the self-reported experiences of the person and reported abnormalities in behavior, followed by a
psychiatric assessment
. The
mental status examination
is an important part of the assessment.
[
165
]
An established tool for assessing the severity of positive and negative symptoms is the
Positive and Negative Syndrome Scale
(PANSS).
[
166
]
This has been seen to have shortcomings relating to negative symptoms, and other scales – the
Clinical Assessment Interview for Negative Symptoms
(CAINS), and the
Brief Negative Symptoms Scale
(BNSS) have been introduced.
[
51
]
The
DSM-5
, published in 2013, gives a
Scale to Assess the Severity of Symptom Dimensions
outlining eight dimensions of symptoms.
[
60
]
DSM-5 states that to be diagnosed with schizophrenia, two diagnostic criteria have to be met over the period of one month, with a significant impact on social or occupational functioning for at least six months. One of the symptoms needs to be either delusions, hallucinations, or disorganized speech. A second symptom could be one of the negative symptoms, or severely disorganized or
catatonic behaviour
.
[
10
]
A different diagnosis of
schizophreniform disorder
can be made before the six months needed for the diagnosis of schizophrenia.
[
10
]
In Australia, the guideline for diagnosis is for six months or more with symptoms severe enough to affect ordinary functioning.
[
167
]
In the UK diagnosis is based on having the symptoms for most of the time for one month, with symptoms that significantly affect the ability to work, study, or carry on ordinary daily living, and with other similar conditions ruled out.
[
168
]
The ICD criteria are typically used in European countries; the DSM criteria are used predominantly in the United States and Canada, and are prevailing in research studies. In practice, agreement between the two systems is high.
[
169
]
The current proposal for the
ICD-11
criteria for schizophrenia recommends adding self-disorder as a symptom.
[
42
]
A major unresolved difference between the two diagnostic systems is that of the requirement in DSM of an impaired functional outcome. WHO for ICD argues that not all people with schizophrenia have functional deficits and so these are not specific for the diagnosis.
[
60
]
Neuroimaging techniques
Functional magnetic resonance imaging (fMRI)
has become a tool in understanding brain activity and connectivity differences in individuals with schizophrenia. Through resting-state fMRI, researchers have observed altered connectivity patterns within several key brain networks, such as the default mode network (DMN),
[
170
]
salience network (SN),
[
171
]
and central executive network (CEN).
[
172
]
Alterations may underlie cognitive and emotional symptoms in schizophrenia, such as disorganized thinking, impaired attention, and emotional dysregulation.
Comorbidities
Euler diagram
showing overlapping
clinical phenotypes
in genes associated with
monogenic forms
of
autism spectrum disorder
(ASD),
dystonia
,
epilepsy
and schizophrenia:
Genes associated with epilepsy
Genes associated with schizophrenia
Genes associated with autism spectrum disorder
Genes associated with dystonia
Many people with schizophrenia may have one or more
other mental disorders
, such as
anxiety disorders
,
obsessive–compulsive disorder
, or substance use disorder. These are separate disorders that require treatment.
[
10
]
When comorbid with schizophrenia, substance use disorder and
antisocial personality disorder
both increase the risk for violence.
[
173
]
Comorbid substance use disorder also increases the risk of suicide.
[
122
]
Sleep disorders
often co-occur with schizophrenia, and may be an early sign of relapse.
[
174
]
Sleep disorders are linked with positive symptoms such as
disorganized thinking
and can adversely affect
cortical plasticity
and cognition.
[
174
]
The consolidation of memories is disrupted in sleep disorders.
[
175
]
They are associated with severity of illness, a poor prognosis, and poor quality of life.
[
176
]
[
177
]
Sleep onset and maintenance insomnia is a common symptom, regardless of whether treatment has been received or not.
[
176
]
Genetic variations have been found associated with these conditions involving the
circadian rhythm
, dopamine and
histamine metabolism
, and signal transduction.
[
178
]
Schizophrenia is also associated with a number of somatic comorbidities including
diabetes mellitus type 2
,
autoimmune diseases
, and
cardiovascular diseases
. The association of these with schizophrenia may be partially due to medications (e.g.
dyslipidemia
from antipsychotics), environmental factors (e.g. complications from an increased rate of cigarette smoking), or associated with the disorder itself (e.g. diabetes mellitus type 2 and some cardiovascular diseases are thought to be genetically linked). These somatic comorbidities contribute to reduced life expectancy among persons with the disorder.
[
179
]
Differential diagnosis
To make a diagnosis of schizophrenia
other possible causes of psychosis need to be excluded
.
[
180
]
:
858
Psychotic symptoms lasting less than a month may be diagnosed as
brief psychotic disorder
, or as schizophreniform disorder. Psychosis is noted in
Other specified schizophrenia spectrum and other psychotic disorders
as a DSM-5 category.
Schizoaffective disorder
is diagnosed if symptoms of
mood disorder
are substantially present alongside psychotic symptoms. Psychosis that results from a general medical condition or substance is termed secondary psychosis.
[
10
]
Psychotic symptoms may be present in several other conditions, including
bipolar disorder
,
[
11
]
borderline personality disorder
,
[
12
]
substance intoxication
,
substance-induced psychosis
, and a number of
drug withdrawal syndromes
. Non-bizarre delusions are also present in
delusional disorder
, and social withdrawal in
social anxiety disorder
,
avoidant personality disorder
and
schizotypal personality disorder
. Schizotypal personality disorder has symptoms that are similar but less severe than those of schizophrenia.
[
10
]
Schizophrenia occurs along with obsessive–compulsive disorder (OCD) considerably more often than could be explained by chance, although it can be difficult to distinguish obsessions that occur in OCD from the delusions of schizophrenia.
[
181
]
There can be considerable overlap with the symptoms of
post-traumatic stress disorder
.
[
182
]
A more general medical and neurological examination may be needed to rule out medical illnesses which may rarely produce psychotic schizophrenia-like symptoms, such as
metabolic disturbance
,
systemic infection
,
syphilis
,
HIV-associated neurocognitive disorder
,
epilepsy
,
limbic encephalitis
, and brain lesions. Stroke,
multiple sclerosis
,
hyperthyroidism
,
hypothyroidism
, and
dementias
such as
Alzheimer's disease
,
Huntington's disease
,
frontotemporal dementia
, and the
Lewy body dementias
may also be associated with schizophrenia-like psychotic symptoms.
[
183
]
It may be necessary to rule out a
delirium
, which can be distinguished by visual hallucinations, acute onset and fluctuating
level of consciousness
, and indicates an underlying medical illness. Investigations are not generally repeated for relapse unless there is a specific
medical
indication or possible
adverse effects
from
antipsychotic medication
.
[
184
]
In children hallucinations must be separated from typical childhood fantasies.
[
10
]
It is difficult to distinguish childhood schizophrenia from autism.
[
73
]
Prevention
Prevention
of schizophrenia is difficult as there are no reliable markers for the later development of the disorder.
[
185
]
Early intervention programs
diagnose and treat patients in the prodromal phase of the illness. There is some evidence that these programs reduce symptoms. Patients tend to prefer early treatment programs to ordinary treatment and are less likely to disengage from them. As of 2020, it is unclear whether the benefits of early treatment persist once the treatment is terminated.
[
186
]
Cognitive behavioral therapy
may reduce the risk of psychosis in those at high risk after a year
[
187
]
and is recommended in this group, by the
National Institute for Health and Care Excellence
(NICE).
[
35
]
Another preventive measure is to avoid drugs that have been associated with development of the disorder, including
cannabis
, cocaine, and
amphetamines
.
[
86
]
Antipsychotics are prescribed following a first-episode psychosis, and following remission, a preventive maintenance use is continued to avoid relapse. However, it is recognized that some people do recover following a single episode and that long-term use of antipsychotics will not be needed but there is no way of identifying this group.
[
188
]
Management
The primary treatment of schizophrenia is the use of
antipsychotic medications
, often in combination with
psychosocial interventions
and
social supports
.
[
28
]
[
189
]
Community support services including drop-in centers, visits by members of a
community mental health team
,
supported employment
,
[
190
]
and support groups are common. The time between the onset of psychotic symptoms to being given treatment – the duration of untreated psychosis (DUP) – is associated with a poorer outcome in both the short term and the long term.
[
191
]
Voluntary
or
involuntary
admission to hospital may be imposed by doctors and courts who deem a person to be having a severe episode. In the UK, large mental hospitals termed asylums began to be closed down in the 1950s with the advent of antipsychotics, and with an awareness of the negative impact of long-term hospital stays on recovery.
[
26
]
This process was known as
deinstitutionalization
, and community and supportive services were developed to support this change. Many other countries followed suit with the US starting in the 60s.
[
192
]
There still remain a smaller group of people who do not improve enough to be discharged.
[
26
]
[
33
]
In some countries that lack the necessary supportive and social services, long-term hospital stays are more usual.
[
34
]
Medication
Risperidone
(trade name Risperdal) is a common
atypical antipsychotic
medication.
Most antipsychotics reduce overall, positive, negative, and depressive symptoms in schizophrenia, with clozapine showing the largest overall effect, though efficacy differences between drugs are mostly gradual.
[
31
]
Side-effect profiles, including weight gain, sedation, prolactin elevation, and QTc prolongation, vary more distinctly; clinicians weigh benefits against risks based on patient factors and preferences.
[
31
]
The first-line treatment for schizophrenia is an antipsychotic. The first-generation antipsychotics, now called
typical antipsychotics
, like
haloperidol
, are
dopamine antagonists
that block D
2
receptors, and affect the
neurotransmission
of
dopamine
. Those brought out later, the second-generation antipsychotics known as
atypical antipsychotics
, including
olanzapine
and
risperidone
, can also have an effect on another neurotransmitter,
serotonin
. Antipsychotics can reduce the symptoms of anxiety within hours of their use, but, for other symptoms, they may take several days or weeks to reach their full effect.
[
37
]
[
193
]
They have little effect on negative and cognitive symptoms, which may be helped by additional psychotherapies and medications.
[
194
]
There is no single antipsychotic suitable for first-line treatment for everyone, as responses and tolerances vary between people.
[
195
]
Stopping medication may be considered after a single psychotic episode where there has been a full recovery with no symptoms for twelve months. Repeated relapses worsen the long-term outlook and the risk of relapse following a second episode is high, and long-term treatment is usually recommended.
[
196
]
[
197
]
About half of those with schizophrenia will respond favourably to antipsychotics, and have a good return of functioning.
[
198
]
However, positive symptoms persist in up to a third of people. Following two trials of different antipsychotics over six weeks, that also prove ineffective, they will be classed as having treatment-resistant schizophrenia (TRS), and
clozapine
will be offered.
[
199
]
[
30
]
Clozapine is of benefit to around half of this group although it has the potentially serious side effect of
agranulocytosis
(lowered
white blood cell
count) in less than 4% of people.
[
28
]
[
86
]
[
200
]
About 30 to 50 percent of people with schizophrenia do not accept that they have an illness or comply with their recommended treatment.
[
201
]
For those who are unwilling or unable to take medication regularly,
long-acting injections
of antipsychotics may be used,
[
202
]
which reduce the risk of relapse to a greater degree than oral medications.
[
203
]
When used in combination with psychosocial interventions, they may improve long-term
adherence
to treatment.
[
204
]
A 2025 meta-analysis showed xanomeline and trospium's effect in the improvement of symptoms of schizophrenia.
[
205
]
The
fixed-dose combination
medication
xanomeline/trospium chloride
(Cobenfy) was approved for medical use in the United States in September 2024.
[
206
]
[
207
]
It is the first
cholinergic agonist
approved by the US
Food and Drug Administration
(FDA) to treat schizophrenia.
[
206
]
Negative and cognitive symptoms are an unmet clinical need in antipsychotic-based treatment approaches. Psychostimulant drugs have been found effective in the treatment of negative symptoms, but are rarely prescribed due to concerns about the excacerbation of positive symptoms.
[
54
]
It is possible that low-dose psychedelic therapies could be of benefit in schizophrenia through their prosocial and procognitive effects, although there is a serious risk that high dose psychedelic therapies could lead to worsening of positive symptoms.
[
208
]
Adverse effects
Extrapyramidal symptoms
, including
akathisia
, are associated with all commercially available
antipsychotic
to varying degrees.
[
209
]
:
566
There is little evidence that second generation antipsychotics have reduced levels of extrapyramidical symptoms compared to typical antipsychotics.
[
209
]
:
566
Tardive dyskinesia
can occur due to long-term use of antipsychotics, developing after months or years of use.
[
210
]
The antipsychotic
clozapine
is also associated with
thromboembolism
(including
pulmonary embolism
),
myocarditis
, and
cardiomyopathy
.
A number of psychosocial interventions that include several types of
psychotherapy
may be useful in the treatment of schizophrenia such as:
family therapy
,
[
211
]
group therapy
, cognitive remediation therapy (CRT),
[
212
]
cognitive behavioral therapy (CBT),
[
213
]
and
metacognitive training
.
[
214
]
[
215
]
Skills training, help with substance use, and weight management – often needed as a side effect of an antipsychotic – are also offered.
[
216
]
In the US, interventions for first episode psychosis have been brought together in an overall approach known as
coordinated speciality care
(CSC) and also includes support for education.
[
37
]
In the UK
care across all phases
is a similar approach that covers many of the treatment guidelines recommended.
[
35
]
The aim is to reduce the number of relapses and stays in the hospital.
[
211
]
Other support services for education, employment, and housing are usually offered. For people with severe schizophrenia, who are discharged from a stay in the hospital, these services are often brought together in an integrated approach to offer support in the community away from the hospital setting. In addition to medicine management, housing, and finances, assistance is given for more routine matters such as help with shopping and using public transport. This approach is known as
assertive community treatment
(ACT) and has been shown to achieve positive results in symptoms, social functioning and quality of life.
[
217
]
[
218
]
Another more intense approach is known as
intensive care management
(ICM). ICM is a stage further than ACT and emphasises support of high intensity in smaller caseloads, (less than twenty). This approach is to provide long-term care in the community. Studies show that ICM improves many of the relevant outcomes including social functioning.
[
219
]
Some studies have shown little evidence for the effectiveness of CBT in either reducing symptoms or preventing relapse.
[
220
]
[
221
]
However, other studies have found that CBT does improve overall psychotic symptoms (when in use with medication) and it has been recommended in Canada, but has been seen to have no effect on social function, relapse, or quality of life.
[
222
]
In the UK it is recommended as an add-on therapy in the treatment of schizophrenia.
[
193
]
[
221
]
Arts therapies
are seen to improve negative symptoms in some people, and are recommended by NICE in the UK.
[
193
]
This approach is criticised as having not been well-researched,
[
223
]
[
224
]
and arts therapies are not recommended in Australian guidelines for example.
[
225
]
Peer support
, in which people with
personal experience
of schizophrenia, provide help to each other, is of unclear benefit.
[
226
]
Other
Exercise including aerobic exercise has been shown to improve positive and negative symptoms, cognition, working memory, and improve quality of life.
[
227
]
[
228
]
Exercise has also been shown to increase the volume of the
hippocampus
in those with schizophrenia. A decrease in hippocampal volume is one of the factors linked to the development of the disease.
[
227
]
However, there still remains the problem of increasing motivation for, and maintaining participation in physical activity.
[
229
]
Supervised sessions are recommended.
[
228
]
In the UK healthy eating advice is offered alongside exercise programs.
[
230
]
An inadequate diet is often found in schizophrenia, and associated vitamin deficiencies including those of
folate
, and
vitamin D
are linked to the risk factors for the development of schizophrenia and for early death including heart disease.
[
231
]
[
232
]
Those with schizophrenia possibly have the worst diet of all the mental disorders. Lower levels of folate and vitamin D have been noted as significantly lower in first episode psychosis.
[
231
]
The use of supplemental folate is recommended.
[
233
]
A
zinc deficiency
has also been noted.
[
234
]
Vitamin B
12
is also often deficient and this is linked to worse symptoms. Supplementation with B vitamins has been shown to significantly improve symptoms, and to put in reverse some of the cognitive deficits.
[
231
]
It is also suggested that the noted dysfunction in gut microbiota might benefit from the use of
probiotics
.
[
234
]
Prognosis
Disability-adjusted life years
lost due to schizophrenia per 100,000 inhabitants in 2004
no data
≤ 185
185–197
197–207
207–218
218–229
229–240
240–251
251–262
262–273
273–284
284–295
≥ 295
Schizophrenia has great human and economic costs.
[
7
]
It decreases life expectancy by between 10
[
13
]
and 28 years.
[
14
]
This is primarily because of its association with heart disease,
[
235
]
diabetes,
[
14
]
obesity
, poor diet, a
sedentary lifestyle
, and smoking, with an increased rate of suicide playing a lesser role.
[
13
]
[
236
]
Side effects of antipsychotics may also increase the risk.
[
13
]
Almost 40% of those with schizophrenia die from complications of cardiovascular disease which is seen to be increasingly associated.
[
232
]
An underlying factor of sudden cardiac death may be
Brugada syndrome
(BrS) – BrS mutations that overlap with those linked with schizophrenia are the
calcium channel
mutations.
[
232
]
BrS may also be drug-induced from certain antipsychotics and antidepressants.
[
232
]
Primary polydipsia
, or excessive fluid intake, is relatively common in people with chronic schizophrenia.
[
237
]
[
238
]
This may lead to
hyponatremia
which can be life-threatening. Antipsychotics can lead to a
dry mouth
, but there are several other factors that may contribute to the disorder; it may reduce life expectancy by 13 percent.
[
238
]
Barriers to improving the mortality rate in schizophrenia are poverty, overlooking the symptoms of other illnesses, stress, stigma, and medication side effects.
[
239
]
[
240
]
[
241
]
Schizophrenia is a major cause of
disability
. In 2016, it was classed as the 12th most disabling condition.
[
242
]
Approximately 75% of people with schizophrenia have ongoing disability with relapses.
[
243
]
Some people do recover completely and others function well in society.
[
244
]
Most people with schizophrenia live independently with community support.
[
28
]
About 85% are unemployed.
[
7
]
In people with a first episode of psychosis in schizophrenia a good long-term outcome occurs in 31%, an intermediate outcome in 42% and a poor outcome in 31%.
[
245
]
Males are affected more often than females, and have a worse outcome.
[
246
]
Studies showing that outcomes for schizophrenia appear better in the
developing
than the
developed world
[
247
]
have been questioned.
[
248
]
Social problems, such as long-term unemployment, poverty, homelessness, exploitation,
stigmatization
and victimization are common consequences, and lead to
social exclusion
.
[
26
]
[
27
]
[
240
]
[
241
]
There is a higher than average
suicide rate
associated with schizophrenia estimated at 5% to 6%, most often occurring in the period following onset or first hospital admission.
[
19
]
[
29
]
Several times more (20 to 40%) attempt suicide at least once.
[
10
]
[
100
]
There are a variety of risk factors, including male sex, depression, a high
IQ
,
[
249
]
heavy smoking,
[
250
]
and substance use.
[
122
]
Repeated relapse is linked to an increased risk of suicidal behavior.
[
188
]
The use of clozapine can reduce the risk of suicide, and of aggression.
[
251
]
A strong association between
schizophrenia and tobacco smoking
has been shown in worldwide studies.
[
252
]
[
253
]
Smoking
is especially high in those diagnosed with schizophrenia, with estimates ranging from 80 to 90% being regular smokers, as compared to 20% of the general population.
[
253
]
Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content.
[
41
]
Some propose that this is in an effort to improve symptoms.
[
254
]
Among people with schizophrenia use of cannabis is also common.
[
122
]
Schizophrenia leads to an increased risk of dementia.
[
255
]
Violence
Most people with schizophrenia are not aggressive, and are more likely to be victims of violence rather than perpetrators.
[
10
]
People with schizophrenia are commonly exploited and victimized by violent crime as part of a broader dynamic of social exclusion.
[
26
]
[
27
]
People diagnosed with schizophrenia are also subject to forced drug injections, seclusion, and restraint at high rates.
[
32
]
[
33
]
The risk of violence by people with schizophrenia is small. There are minor subgroups where the risk is high.
[
173
]
This risk is usually associated with a comorbid disorder such as a substance use disorder – in particular alcohol, or with antisocial personality disorder.
[
173
]
Substance use disorder is strongly linked, and other risk factors are linked to deficits in cognition and social cognition including facial perception and insight that are in part included in
theory of mind
impairments.
[
256
]
[
257
]
Poor cognitive functioning, decision-making, and facial perception may contribute to making a wrong judgement of a situation that could result in an inappropriate response such as violence.
[
258
]
These associated risk factors are also present in antisocial personality disorder which when present as a comorbid disorder greatly increases the risk of violence.
[
259
]
[
260
]
Epidemiology
Deaths per million persons due to schizophrenia in 2012
0–0
1–1
2–2
3–3
4–6
7–20
In 2017,
[
needs update
]
the
Global Burden of Disease Study
estimated there were 1.1 million new cases;
[
21
]
in 2022 the World Health Organization (WHO) reported a total of 24 million cases globally.
[
2
]
Schizophrenia affects around 0.3–0.7% of people at some point in their life.
[
20
]
[
14
]
In areas of conflict this figure can rise to between 4.0 and 6.5%.
[
261
]
It occurs 1.4 times more frequently in males than females and typically appears earlier in men.
[
86
]
Worldwide, schizophrenia is the most common
psychotic disorder
.
[
57
]
The frequency of schizophrenia varies across the world,
[
10
]
within countries,
[
262
]
and at the local and neighborhood level;
[
263
]
this variation in
prevalence
between studies over time, across geographical locations, and by gender is as high as fivefold.
[
7
]
Schizophrenia causes approximately one percent of worldwide
disability adjusted life years
[
needs update
]
[
86
]
and resulted in 17,000 deaths in 2015.
[
16
]
In 2000,
[
needs update
]
WHO found the percentage of people affected and the number of new cases that develop each year is roughly similar around the world, with age-standardized prevalence per 100,000 ranging from 343 in Africa to 544 in Japan and Oceania for men, and from 378 in Africa to 527 in Southeastern Europe for women.
[
264
]
History
Conceptual development
The term "schizophrenia" was coined by
Eugen Bleuler
.
Accounts of a schizophrenia-like
syndrome
are rare in records before the 19th century; the earliest case reports were in 1797 and 1809.
[
265
]
The term
dementia praecox
("premature dementia") was used by German psychiatrist Heinrich Schüle in 1886 and then in 1891 by
Arnold Pick
in a case report of
hebephrenia
. In 1893
Emil Kraepelin
used the term in making a distinction, known as the
Kraepelinian dichotomy
, between the two psychoses: dementia praecox and
manic depression
(now called
bipolar disorder
).
[
13
]
When it became evident that the disorder was not a degenerative dementia, it was renamed
schizophrenia
by
Eugen Bleuler
in 1908.
[
266
]
The word
schizophrenia
("splitting of the mind") is
Modern Latin
, derived from the
Greek
schizein
(
Ancient Greek
:
σχίζειν
,
lit.
'
to split
'
) and
phrēn
(
Ancient Greek
:
φρήν
,
lit.
'
mind
'
).
[
267
]
Its use was intended to describe the separation of function between
personality
,
thinking
, memory, and perception.
[
266
]
In the early 20th century, the psychiatrist
Kurt Schneider
categorized the psychotic symptoms of schizophrenia into two groups: hallucinations and delusions. The hallucinations were listed as specific to auditory and the delusions included thought disorders. These were seen as important symptoms, termed
first-rank
. The most common first-rank symptom was found to belong to thought disorders.
[
page needed
]
[
268
]
[
page needed
]
[
269
]
In 2013 the first-rank symptoms were excluded from the DSM-5 criteria;
[
270
]
while they may not be useful in diagnosing schizophrenia, they can assist in
differential diagnosis
.
[
271
]
Subtypes of schizophrenia—classified as paranoid, disorganized,
catatonic
, undifferentiated, and residual—were difficult to distinguish and are no longer recognized as separate conditions by DSM-5 (2013) or ICD-11.
[
272
]
[
273
]
[
274
]
Breadth of diagnosis
Before the 1960s, nonviolent
petty criminals
and women were sometimes diagnosed with schizophrenia, categorizing the latter as ill for not performing their duties as wives and mothers.
[
275
]
In the mid- to late 1960s, black men were categorized as "hostile and aggressive" and diagnosed as schizophrenic at much higher rates, their
civil rights
and
Black Power
activism labeled as delusions.
[
275
]
[
276
]
In the early 1970s in the United States, the diagnostic model for schizophrenia was broad and clinically based using
DSM II
. Schizophrenia was diagnosed far more in the United States than in Europe, where the
ICD-9
criteria were followed. The US model was criticised for failing to demarcate clearly those people with a mental illness. In 1980 DSM III was published and showed a shift in focus from the clinically based
biopsychosocial model
to a reason-based medical model.
[
clarification needed
]
[
277
]
DSM IV brought an increased focus on an evidence-based medical model.
[
278
]
Historical treatment
A molecule of
chlorpromazine
, the first antipsychotic developed in the 1950s
In the 1930s a number of shock procedures which induced seizures (convulsions) or comas were used to treat schizophrenia.
[
279
]
Insulin shock
involved injecting large doses of
insulin
to induce comas, which in turn produced
hypoglycemia
and convulsions.
[
279
]
[
280
]
The use of electricity to induce seizures was in use as
electroconvulsive therapy
(ECT) by 1938.
[
281
]
Carried out from the 1930s until the 1970s in the United States and until the 1980s in France,
psychosurgery
, including such modalities as the
lobotomy
, is recognized as a
human rights abuse
.
[
282
]
[
283
]
In the mid-1950s,
chlorpromazine
, the first
typical antipsychotic
, was introduced,
[
284
]
followed in the 1970s by clozapine, the first
atypical antipsychotic
.
[
285
]
Political abuse
From the 1960s until 1989, psychiatrists in the
USSR
and
Eastern Bloc
diagnosed thousands of people with
sluggish schizophrenia
,
[
286
]
[
287
]
without signs of psychosis, based on "the assumption that symptoms would later appear".
[
288
]
Now discredited, the diagnosis provided a convenient way to confine political dissidents.
[
289
]
Society and culture
In the United States, the annual cost of schizophrenia – including direct costs (outpatient, inpatient, drugs, and long-term care) and non-healthcare costs (law enforcement, reduced workplace productivity, and unemployment) – was estimated at $62.7 billion for the year 2002.
[
290
]
[
a
]
In the UK the cost in 2016 was put at £11.8 billion per year with a third of that figure directly attributable to the cost of hospital, social care and treatment.
[
7
]
Stigma
John Nash
, an American mathematician and joint recipient of the 1994
Nobel Memorial Prize in Economic Sciences
, had schizophrenia. His life was the subject of the 1998 book,
A Beautiful Mind
, by
Sylvia Nasar
.
In 2002, the term for schizophrenia in Japan was changed from
seishin-bunretsu-byō
(
精神分裂病
; lit. 'mind-split disease')
to
tōgō-shitchō-shō
(
統合失調症
; lit. 'integration–dysregulation syndrome')
to reduce
stigma
and confusion with "multiple personalities".
[
293
]
The new name, also interpreted as "integration disorder", was inspired by the biopsychosocial model.
[
294
]
A similar change was made in South Korea in 2012 to attunement disorder.
[
295
]
Stigma may prevent further research and treatment as in history treated some in the past invariably worse to recovery.
[
240
]
[
241
]
Cultural depictions
Media coverage, especially movies, reinforce the public perception of an association between schizophrenia and violence.
[
296
]
[
241
]
[
240
]
A majority of movies have historically depicted characters with schizophrenia as criminal, dangerous, violent, unpredictable and homicidal, and depicted delusions and hallucinations as the main symptoms of schizophrenic characters, ignoring other common symptoms,
[
297
]
furthering stereotypes of schizophrenia including the idea of a split personality.
[
298
]
The book
A Beautiful Mind
chronicled the life of
John Forbes Nash
who had been diagnosed with schizophrenia and won the
Nobel Memorial Prize in Economic Sciences
. The book was made into a
film with the same name
; an earlier documentary film was
A Brilliant Madness
.
In the UK, guidelines for reporting conditions and award campaigns have shown a reduction in negative reporting since 2013.
[
299
]
In 1964 a
case study
of three males diagnosed with schizophrenia who each had the delusional belief that they were
Jesus Christ
was published as
The Three Christs of Ypsilanti
; a film with the title
Three Christs
was released in 2020.
[
300
]
[
301
]
Research
A 2015 Cochrane review found unclear evidence of benefit from brain stimulation techniques to treat the positive symptoms of schizophrenia, in particular auditory verbal hallucinations (AVHs).
[
302
]
Most studies focus on
transcranial direct-current stimulation
(tDCM), and
repetitive transcranial magnetic stimulation
(rTMS).
[
303
]
Techniques based on focused ultrasound for
deep brain stimulation
could provide insight for the treatment of AVHs.
[
303
]
The study of potential
biomarkers
that would help in diagnosis and treatment of schizophrenia is an active area of research as of 2020. Possible biomarkers include markers of inflammation,
[
99
]
neuroimaging
,
[
304
]
brain-derived neurotrophic factor
(BDNF),
[
305
]
and speech analysis. Some markers such as
C-reactive protein
are useful in detecting levels of inflammation implicated in some psychiatric disorders but they are not disorder-specific. Other inflammatory cytokines are found to be elevated in first episode psychosis and acute relapse that are normalized after treatment with antipsychotics, and these may be considered as state markers.
[
306
]
Deficits in
sleep spindles
in schizophrenia may serve as a marker of an impaired thalamocortical circuit, and a mechanism for memory impairment.
[
175
]
MicroRNAs
are highly influential in early neuronal development, and their disruption is implicated in several
CNS
disorders;
circulating microRNAs
(cimiRNAs) are found in
body fluids
such as blood and cerebrospinal fluid, and changes in their levels are seen to relate to changes in microRNA levels in specific regions of brain tissue. These studies suggest that cimiRNAs have the potential to be early and accurate biomarkers in a number of disorders including schizophrenia.
[
307
]
[
308
]
Ongoing fMRI research
aims to identify biomarkers within these brain networks,
[
309
]
potentially aiding in earlier diagnosis and better tracking of treatment responses in schizophrenia.
Explanatory notes
^
A 2007 review stated that the 2002 estimate was still the best available,
[
291
]
and a 2018 review cited the same $62.7 billion.
[
292
]
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External links
Schizophrenia: Evolution and Synthesis
The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia, Third Edition |
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## Contents
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- [(Top)](https://en.wikipedia.org/wiki/Schizophrenia)
- [1 Signs and symptoms](https://en.wikipedia.org/wiki/Schizophrenia#Signs_and_symptoms)
Toggle Signs and symptoms subsection
- [1\.1 Positive symptoms](https://en.wikipedia.org/wiki/Schizophrenia#Positive_symptoms)
- [1\.2 Negative symptoms](https://en.wikipedia.org/wiki/Schizophrenia#Negative_symptoms)
- [1\.3 Cognitive symptoms](https://en.wikipedia.org/wiki/Schizophrenia#Cognitive_symptoms)
- [1\.4 Onset](https://en.wikipedia.org/wiki/Schizophrenia#Onset)
- [2 Risk factors](https://en.wikipedia.org/wiki/Schizophrenia#Risk_factors)
Toggle Risk factors subsection
- [2\.1 Genetic](https://en.wikipedia.org/wiki/Schizophrenia#Genetic)
- [2\.2 Environmental](https://en.wikipedia.org/wiki/Schizophrenia#Environmental)
- [2\.2.1 Substance use](https://en.wikipedia.org/wiki/Schizophrenia#Substance_use)
- [3 Causes](https://en.wikipedia.org/wiki/Schizophrenia#Causes)
- [4 Diagnosis](https://en.wikipedia.org/wiki/Schizophrenia#Diagnosis)
Toggle Diagnosis subsection
- [4\.1 Criteria](https://en.wikipedia.org/wiki/Schizophrenia#Criteria)
- [4\.2 Neuroimaging techniques](https://en.wikipedia.org/wiki/Schizophrenia#Neuroimaging_techniques)
- [4\.3 Comorbidities](https://en.wikipedia.org/wiki/Schizophrenia#Comorbidities)
- [4\.4 Differential diagnosis](https://en.wikipedia.org/wiki/Schizophrenia#Differential_diagnosis)
- [5 Prevention](https://en.wikipedia.org/wiki/Schizophrenia#Prevention)
- [6 Management](https://en.wikipedia.org/wiki/Schizophrenia#Management)
Toggle Management subsection
- [6\.1 Medication](https://en.wikipedia.org/wiki/Schizophrenia#Medication)
- [6\.1.1 Adverse effects](https://en.wikipedia.org/wiki/Schizophrenia#Adverse_effects)
- [6\.2 Psychosocial interventions](https://en.wikipedia.org/wiki/Schizophrenia#Psychosocial_interventions)
- [6\.3 Other](https://en.wikipedia.org/wiki/Schizophrenia#Other)
- [7 Prognosis](https://en.wikipedia.org/wiki/Schizophrenia#Prognosis)
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- [7\.1 Violence](https://en.wikipedia.org/wiki/Schizophrenia#Violence)
- [8 Epidemiology](https://en.wikipedia.org/wiki/Schizophrenia#Epidemiology)
- [9 History](https://en.wikipedia.org/wiki/Schizophrenia#History)
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- [9\.1 Conceptual development](https://en.wikipedia.org/wiki/Schizophrenia#Conceptual_development)
- [9\.2 Breadth of diagnosis](https://en.wikipedia.org/wiki/Schizophrenia#Breadth_of_diagnosis)
- [9\.3 Historical treatment](https://en.wikipedia.org/wiki/Schizophrenia#Historical_treatment)
- [9\.4 Political abuse](https://en.wikipedia.org/wiki/Schizophrenia#Political_abuse)
- [10 Society and culture](https://en.wikipedia.org/wiki/Schizophrenia#Society_and_culture)
Toggle Society and culture subsection
- [10\.1 Stigma](https://en.wikipedia.org/wiki/Schizophrenia#Stigma)
- [10\.2 Cultural depictions](https://en.wikipedia.org/wiki/Schizophrenia#Cultural_depictions)
- [11 Research](https://en.wikipedia.org/wiki/Schizophrenia#Research)
- [12 Explanatory notes](https://en.wikipedia.org/wiki/Schizophrenia#Explanatory_notes)
- [13 References](https://en.wikipedia.org/wiki/Schizophrenia#References)
- [14 External links](https://en.wikipedia.org/wiki/Schizophrenia#External_links)
Toggle the table of contents
# Schizophrenia
105 languages
- [Afrikaans](https://af.wikipedia.org/wiki/Skisofrenie "Skisofrenie – Afrikaans")
- [Alemannisch](https://als.wikipedia.org/wiki/Schizophrenie "Schizophrenie – Alemannic")
- [Aragonés](https://an.wikipedia.org/wiki/Esquizofrenia "Esquizofrenia – Aragonese")
- [العربية](https://ar.wikipedia.org/wiki/%D9%81%D8%B5%D8%A7%D9%85 "فصام – Arabic")
- [الدارجة](https://ary.wikipedia.org/wiki/%D8%AA%D8%A7%D8%B3%D9%83%D9%8A%D8%B2%D9%88%D9%81%D8%B1%D9%8A%D9%86%D9%8A%D8%AA "تاسكيزوفرينيت – Moroccan Arabic")
- [مصرى](https://arz.wikipedia.org/wiki/%D8%B4%D9%8A%D8%B2%D9%88%D9%81%D8%B1%D9%8A%D9%86%D9%8A%D8%A7 "شيزوفرينيا – Egyptian Arabic")
- [অসমীয়া](https://as.wikipedia.org/wiki/%E0%A6%B8%E0%A7%8D%E0%A6%95%E0%A6%BF%E0%A6%9C%27%E0%A6%AB%E0%A7%8D%E0%A7%B0%E0%A7%87%E0%A6%A8%E0%A6%BF%E0%A6%AF%E0%A6%BC%E0%A6%BE "স্কিজ'ফ্ৰেনিয়া – Assamese")
- [Asturianu](https://ast.wikipedia.org/wiki/Esquizofrenia "Esquizofrenia – Asturian")
- [Azərbaycanca](https://az.wikipedia.org/wiki/%C5%9Eizofreniya "Şizofreniya – Azerbaijani")
- [تۆرکجه](https://azb.wikipedia.org/wiki/%D8%A7%DB%8C%D8%B3%DA%A9%DB%8C%D8%B2%D9%88%D9%81%D8%B1%D9%86%DB%8C "ایسکیزوفرنی – South Azerbaijani")
- [Беларуская (тарашкевіца)](https://be-tarask.wikipedia.org/wiki/%D0%A8%D1%8B%D0%B7%D0%B0%D1%84%D1%80%D1%8D%D0%BD%D1%96%D1%8F "Шызафрэнія – Belarusian (Taraškievica orthography)")
- [Беларуская](https://be.wikipedia.org/wiki/%D0%A8%D1%8B%D0%B7%D0%B0%D1%84%D1%80%D1%8D%D0%BD%D1%96%D1%8F "Шызафрэнія – Belarusian")
- [Български](https://bg.wikipedia.org/wiki/%D0%A8%D0%B8%D0%B7%D0%BE%D1%84%D1%80%D0%B5%D0%BD%D0%B8%D1%8F "Шизофрения – Bulgarian")
- [বাংলা](https://bn.wikipedia.org/wiki/%E0%A6%AD%E0%A6%97%E0%A7%8D%E0%A6%A8%E0%A6%AE%E0%A6%A8%E0%A6%B8%E0%A7%8D%E0%A6%95%E0%A6%A4%E0%A6%BE "ভগ্নমনস্কতা – Bangla")
- [Bosanski](https://bs.wikipedia.org/wiki/Shizofrenija "Shizofrenija – Bosnian")
- [Català](https://ca.wikipedia.org/wiki/Esquizofr%C3%A8nia "Esquizofrènia – Catalan")
- [کوردی](https://ckb.wikipedia.org/wiki/%D8%B4%DB%8C%D8%B2%DB%86%D9%81%D8%B1%DB%8E%D9%86%DB%8C%D8%A7 "شیزۆفرێنیا – Central Kurdish")
- [Čeština](https://cs.wikipedia.org/wiki/Schizofrenie "Schizofrenie – Czech")
- [Cymraeg](https://cy.wikipedia.org/wiki/Sgitsoffrenia "Sgitsoffrenia – Welsh")
- [Dansk](https://da.wikipedia.org/wiki/Skizofreni "Skizofreni – Danish")
- [Deutsch](https://de.wikipedia.org/wiki/Schizophrenie "Schizophrenie – German")
- [Ελληνικά](https://el.wikipedia.org/wiki/%CE%A3%CF%87%CE%B9%CE%B6%CE%BF%CF%86%CF%81%CE%AD%CE%BD%CE%B5%CE%B9%CE%B1 "Σχιζοφρένεια – Greek")
- [Esperanto](https://eo.wikipedia.org/wiki/Skizofrenio "Skizofrenio – Esperanto")
- [Español](https://es.wikipedia.org/wiki/Esquizofrenia "Esquizofrenia – Spanish")
- [Eesti](https://et.wikipedia.org/wiki/Skisofreenia "Skisofreenia – Estonian")
- [Euskara](https://eu.wikipedia.org/wiki/Eskizofrenia "Eskizofrenia – Basque")
- [فارسی](https://fa.wikipedia.org/wiki/%D8%A7%D8%B3%DA%A9%DB%8C%D8%B2%D9%88%D9%81%D8%B1%D9%86%DB%8C "اسکیزوفرنی – Persian")
- [Suomi](https://fi.wikipedia.org/wiki/Skitsofrenia "Skitsofrenia – Finnish")
- [Français](https://fr.wikipedia.org/wiki/Schizophr%C3%A9nie "Schizophrénie – French")
- [Gaeilge](https://ga.wikipedia.org/wiki/Scitsifr%C3%A9ine "Scitsifréine – Irish")
- [Kriyòl gwiyannen](https://gcr.wikipedia.org/wiki/Skizofr%C3%A9ni "Skizofréni – Guianan Creole")
- [Galego](https://gl.wikipedia.org/wiki/Esquizofrenia "Esquizofrenia – Galician")
- [Ghanaian Pidgin](https://gpe.wikipedia.org/wiki/Schizophrenia "Schizophrenia – Ghanaian Pidgin")
- [Hausa](https://ha.wikipedia.org/wiki/Hauka "Hauka – Hausa")
- [עברית](https://he.wikipedia.org/wiki/%D7%A1%D7%9B%D7%99%D7%96%D7%95%D7%A4%D7%A8%D7%A0%D7%99%D7%94 "סכיזופרניה – Hebrew")
- [हिन्दी](https://hi.wikipedia.org/wiki/%E0%A4%AE%E0%A4%A8%E0%A5%8B%E0%A4%B5%E0%A4%BF%E0%A4%A6%E0%A4%B2%E0%A4%A4%E0%A4%BE "मनोविदलता – Hindi")
- [Hrvatski](https://hr.wikipedia.org/wiki/Shizofrenija "Shizofrenija – Croatian")
- [Magyar](https://hu.wikipedia.org/wiki/Szkizofr%C3%A9nia "Szkizofrénia – Hungarian")
- [Հայերեն](https://hy.wikipedia.org/wiki/%D5%87%D5%AB%D5%A6%D5%B8%D6%86%D6%80%D5%A5%D5%B6%D5%AB%D5%A1 "Շիզոֆրենիա – Armenian")
- [Interlingua](https://ia.wikipedia.org/wiki/Schizophrenia "Schizophrenia – Interlingua")
- [Bahasa Indonesia](https://id.wikipedia.org/wiki/Skizofrenia "Skizofrenia – Indonesian")
- [Ido](https://io.wikipedia.org/wiki/Skizofrenio "Skizofrenio – Ido")
- [Íslenska](https://is.wikipedia.org/wiki/Ge%C3%B0klofi "Geðklofi – Icelandic")
- [Italiano](https://it.wikipedia.org/wiki/Schizofrenia "Schizofrenia – Italian")
- [日本語](https://ja.wikipedia.org/wiki/%E7%B5%B1%E5%90%88%E5%A4%B1%E8%AA%BF%E7%97%87 "統合失調症 – Japanese")
- [Jawa](https://jv.wikipedia.org/wiki/Skizofr%C3%A9nia "Skizofrénia – Javanese")
- [ქართული](https://ka.wikipedia.org/wiki/%E1%83%A8%E1%83%98%E1%83%96%E1%83%9D%E1%83%A4%E1%83%A0%E1%83%94%E1%83%9C%E1%83%98%E1%83%90 "შიზოფრენია – Georgian")
- [Қазақша](https://kk.wikipedia.org/wiki/%D0%A8%D0%B8%D0%B7%D0%BE%D1%84%D1%80%D0%B5%D0%BD%D0%B8%D1%8F "Шизофрения – Kazakh")
- [ಕನ್ನಡ](https://kn.wikipedia.org/wiki/%E0%B2%87%E0%B2%9A%E0%B3%8D%E0%B2%9B%E0%B2%BF%E0%B2%A4%E0%B3%8D%E0%B2%A4_%E0%B2%B5%E0%B2%BF%E0%B2%95%E0%B2%B2%E0%B2%A4%E0%B3%86 "ಇಚ್ಛಿತ್ತ ವಿಕಲತೆ – Kannada")
- [한국어](https://ko.wikipedia.org/wiki/%EC%A1%B0%ED%98%84%EB%B3%91 "조현병 – Korean")
- [Kurdî](https://ku.wikipedia.org/wiki/%C5%9E%C3%AEzofren%C3%AE "Şîzofrenî – Kurdish")
- [Кыргызча](https://ky.wikipedia.org/wiki/%D0%A8%D0%B8%D0%B7%D0%BE%D1%84%D1%80%D0%B5%D0%BD%D0%B8%D1%8F "Шизофрения – Kyrgyz")
- [Latina](https://la.wikipedia.org/wiki/Schizophrenia "Schizophrenia – Latin")
- [Lingua Franca Nova](https://lfn.wikipedia.org/wiki/Scizofrenia "Scizofrenia – Lingua Franca Nova")
- [Luganda](https://lg.wikipedia.org/wiki/Okutabuka_omutwe_\(Schizophrenia\) "Okutabuka omutwe (Schizophrenia) – Ganda")
- [Lietuvių](https://lt.wikipedia.org/wiki/%C5%A0izofrenija "Šizofrenija – Lithuanian")
- [Latviešu](https://lv.wikipedia.org/wiki/%C5%A0izofr%C4%93nija "Šizofrēnija – Latvian")
- [Македонски](https://mk.wikipedia.org/wiki/%D0%A8%D0%B8%D0%B7%D0%BE%D1%84%D1%80%D0%B5%D0%BD%D0%B8%D1%98%D0%B0 "Шизофренија – Macedonian")
- [മലയാളം](https://ml.wikipedia.org/wiki/%E0%B4%B8%E0%B5%8D%E0%B4%95%E0%B4%BF%E0%B4%B8%E0%B5%8B%E0%B4%AB%E0%B5%8D%E0%B4%B0%E0%B5%80%E0%B4%A8%E0%B4%BF%E0%B4%AF "സ്കിസോഫ്രീനിയ – Malayalam")
- [मराठी](https://mr.wikipedia.org/wiki/%E0%A4%9B%E0%A4%BF%E0%A4%A8%E0%A5%8D%E2%80%8D%E0%A4%A8%E0%A4%AE%E0%A4%A8%E0%A4%B8%E0%A5%8D%E0%A4%95%E0%A4%A4%E0%A4%BE "छिन्नमनस्कता – Marathi")
- [Bahasa Melayu](https://ms.wikipedia.org/wiki/Skizofrenia "Skizofrenia – Malay")
- [မြန်မာဘာသာ](https://my.wikipedia.org/wiki/%E1%80%85%E1%80%AD%E1%80%90%E1%80%BA%E1%80%80%E1%80%85%E1%80%89%E1%80%B7%E1%80%BA%E1%80%80%E1%80%9C%E1%80%BB%E1%80%AC%E1%80%B8%E1%80%9B%E1%80%B1%E1%80%AC%E1%80%82%E1%80%AB "စိတ်ကစဉ့်ကလျားရောဂါ – Burmese")
- [مازِرونی](https://mzn.wikipedia.org/wiki/%D8%A7%D8%B3%DA%A9%DB%8C%D8%B2%D9%88%D9%81%D8%B1%D9%86%DB%8C "اسکیزوفرنی – Mazanderani")
- [Nederlands](https://nl.wikipedia.org/wiki/Schizofrenie "Schizofrenie – Dutch")
- [Norsk nynorsk](https://nn.wikipedia.org/wiki/Schizofreni "Schizofreni – Norwegian Nynorsk")
- [Norsk bokmål](https://no.wikipedia.org/wiki/Schizofreni "Schizofreni – Norwegian Bokmål")
- [Chi-Chewa](https://ny.wikipedia.org/wiki/Schizophrenia "Schizophrenia – Nyanja")
- [ଓଡ଼ିଆ](https://or.wikipedia.org/wiki/%E0%AC%B8%E0%AC%BF%E0%AC%9C%E0%AD%8B%E0%AC%AB%E0%AD%8D%E0%AC%B0%E0%AD%87%E0%AC%A8%E0%AC%BF%E0%AC%86 "ସିଜୋଫ୍ରେନିଆ – Odia")
- [ਪੰਜਾਬੀ](https://pa.wikipedia.org/wiki/%E0%A8%A6%E0%A9%81%E0%A8%AB%E0%A8%BE%E0%A9%9C_%E0%A8%AE%E0%A8%BE%E0%A8%A8%E0%A8%B8%E0%A8%BF%E0%A8%95%E0%A8%A4%E0%A8%BE "ਦੁਫਾੜ ਮਾਨਸਿਕਤਾ – Punjabi")
- [Polski](https://pl.wikipedia.org/wiki/Schizofrenia "Schizofrenia – Polish")
- [Português](https://pt.wikipedia.org/wiki/Esquizofrenia "Esquizofrenia – Portuguese")
- [Runa Simi](https://qu.wikipedia.org/wiki/Waq%27akay "Waq'akay – Quechua")
- [Ikirundi](https://rn.wikipedia.org/wiki/Kwamana_ubwoba_wicura_abansi_n%E2%80%99ibikugirira_nabi "Kwamana ubwoba wicura abansi n’ibikugirira nabi – Rundi")
- [Română](https://ro.wikipedia.org/wiki/Schizofrenie "Schizofrenie – Romanian")
- [Русский](https://ru.wikipedia.org/wiki/%D0%A8%D0%B8%D0%B7%D0%BE%D1%84%D1%80%D0%B5%D0%BD%D0%B8%D1%8F "Шизофрения – Russian")
- [Саха тыла](https://sah.wikipedia.org/wiki/%D0%91%D1%8B%D1%80%D0%B0%D1%85%D1%82%D0%B0%D1%80%D1%8B%D1%8B "Бырахтарыы – Yakut")
- [Sicilianu](https://scn.wikipedia.org/wiki/Schizzufrin%C3%ACa "Schizzufrinìa – Sicilian")
- [سنڌي](https://sd.wikipedia.org/wiki/%D8%B4%D9%8A%D8%B2%D9%88%D9%81%D8%B1%D9%8A%D9%86%D9%8A%D8%A7 "شيزوفرينيا – Sindhi")
- [Srpskohrvatski / српскохрватски](https://sh.wikipedia.org/wiki/Shizofrenija "Shizofrenija – Serbo-Croatian")
- [Taclḥit](https://shi.wikipedia.org/wiki/Taskizufrinit "Taskizufrinit – Tachelhit")
- [සිංහල](https://si.wikipedia.org/wiki/%E0%B6%B7%E0%B7%92%E0%B6%B1%E0%B7%8A%E0%B6%B1%E0%B7%9D%E0%B6%B1%E0%B7%8A%E0%B6%B8%E0%B7%8F%E0%B6%AF%E0%B6%BA "භින්නෝන්මාදය – Sinhala")
- [Simple English](https://simple.wikipedia.org/wiki/Schizophrenia "Schizophrenia – Simple English")
- [Slovenčina](https://sk.wikipedia.org/wiki/Schizofr%C3%A9nia "Schizofrénia – Slovak")
- [Slovenščina](https://sl.wikipedia.org/wiki/Shizofrenija "Shizofrenija – Slovenian")
- [Soomaaliga](https://so.wikipedia.org/wiki/Iskiitsofiriiniya "Iskiitsofiriiniya – Somali")
- [Shqip](https://sq.wikipedia.org/wiki/Skizofrenia "Skizofrenia – Albanian")
- [Српски / srpski](https://sr.wikipedia.org/wiki/%D0%A8%D0%B8%D0%B7%D0%BE%D1%84%D1%80%D0%B5%D0%BD%D0%B8%D1%98%D0%B0 "Шизофренија – Serbian")
- [Sunda](https://su.wikipedia.org/wiki/Skizofr%C3%A9nia "Skizofrénia – Sundanese")
- [Svenska](https://sv.wikipedia.org/wiki/Schizofreni "Schizofreni – Swedish")
- [Kiswahili](https://sw.wikipedia.org/wiki/Skizofrenia "Skizofrenia – Swahili")
- [தமிழ்](https://ta.wikipedia.org/wiki/%E0%AE%AE%E0%AE%A9%E0%AE%AA%E0%AF%8D%E0%AE%AA%E0%AE%BF%E0%AE%A4%E0%AF%8D%E0%AE%A4%E0%AF%81 "மனப்பித்து – Tamil")
- [తెలుగు](https://te.wikipedia.org/wiki/%E0%B0%B8%E0%B1%8D%E0%B0%95%E0%B0%BF%E0%B0%9C%E0%B1%8B%E0%B0%AB%E0%B1%8D%E0%B0%B0%E0%B1%80%E0%B0%A8%E0%B0%BF%E0%B0%AF%E0%B0%BE "స్కిజోఫ్రీనియా – Telugu")
- [ไทย](https://th.wikipedia.org/wiki/%E0%B9%82%E0%B8%A3%E0%B8%84%E0%B8%88%E0%B8%B4%E0%B8%95%E0%B9%80%E0%B8%A0%E0%B8%97 "โรคจิตเภท – Thai")
- [Tagalog](https://tl.wikipedia.org/wiki/Schizophrenia "Schizophrenia – Tagalog")
- [Türkçe](https://tr.wikipedia.org/wiki/%C5%9Eizofreni "Şizofreni – Turkish")
- [Українська](https://uk.wikipedia.org/wiki/%D0%A8%D0%B8%D0%B7%D0%BE%D1%84%D1%80%D0%B5%D0%BD%D1%96%D1%8F "Шизофренія – Ukrainian")
- [اردو](https://ur.wikipedia.org/wiki/%D8%B4%DB%8C%D8%B2%D9%88%D9%81%D8%B1%DB%8C%D9%86%DB%8C%D8%A7 "شیزوفرینیا – Urdu")
- [Oʻzbekcha / ўзбекча](https://uz.wikipedia.org/wiki/Shizofreniya "Shizofreniya – Uzbek")
- [Vepsän kel’](https://vep.wikipedia.org/wiki/%C5%A0izofrenii "Šizofrenii – Veps")
- [Tiếng Việt](https://vi.wikipedia.org/wiki/T%C3%A2m_th%E1%BA%A7n_ph%C3%A2n_li%E1%BB%87t "Tâm thần phân liệt – Vietnamese")
- [Winaray](https://war.wikipedia.org/wiki/Eskisofrenya "Eskisofrenya – Waray")
- [Wolof](https://wo.wikipedia.org/wiki/Schizophrenia "Schizophrenia – Wolof")
- [吴语](https://wuu.wikipedia.org/wiki/%E7%B2%BE%E7%A5%9E%E5%88%86%E8%A3%82%E7%97%87 "精神分裂症 – Wu")
- [粵語](https://zh-yue.wikipedia.org/wiki/%E7%B2%BE%E7%A5%9E%E5%88%86%E8%A3%82 "精神分裂 – Cantonese")
- [中文](https://zh.wikipedia.org/wiki/%E7%B2%BE%E7%A5%9E%E5%88%86%E8%A3%82%E7%97%87 "精神分裂症 – Chinese")
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- [Article](https://en.wikipedia.org/wiki/Schizophrenia "View the content page [c]")
- [Talk](https://en.wikipedia.org/wiki/Talk:Schizophrenia "Discuss improvements to the content page [t]")
English
- [Read](https://en.wikipedia.org/wiki/Schizophrenia)
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- [What links here](https://en.wikipedia.org/wiki/Special:WhatLinksHere/Schizophrenia "List of all English Wikipedia pages containing links to this page [j]")
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- [Wikimedia Commons](https://commons.wikimedia.org/wiki/Category:Schizophrenia)
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From Wikipedia, the free encyclopedia
Mental disorder with psychotic symptoms
For other uses, see [Schizophrenia (disambiguation)](https://en.wikipedia.org/wiki/Schizophrenia_\(disambiguation\) "Schizophrenia (disambiguation)").
Medical condition
| Schizophrenia | |
|---|---|
| [](https://en.wikipedia.org/wiki/File:Cloth_embroidered_by_a_schizophrenia_sufferer.jpg) | |
| Cloth [embroidered](https://en.wikipedia.org/wiki/Embroidered "Embroidered") by a person diagnosed with schizophrenia | |
| Pronunciation | [/ˌskɪtsəˈfriːniə/](https://en.wikipedia.org/wiki/Help:IPA/English "Help:IPA/English") [ⓘ](https://en.wikipedia.org/wiki/File:En-us-schizophrenia.ogg "File:En-us-schizophrenia.ogg") [*SKIT\-sə-FREE\-nee-ə*](https://en.wikipedia.org/wiki/Help:Pronunciation_respelling_key "Help:Pronunciation respelling key"), [US](https://en.wikipedia.org/wiki/American_English "American English") also [/ˌskɪtsəˈfrɛniə/](https://en.wikipedia.org/wiki/Help:IPA/English "Help:IPA/English") [ⓘ](https://en.wikipedia.org/wiki/File:LL-Q1860_\(eng\)-Flame,_not_lame-Schizophrenia.wav "File:LL-Q1860 (eng)-Flame, not lame-Schizophrenia.wav") [*SKIT\-sə-FREN\-ee-ə*](https://en.wikipedia.org/wiki/Help:Pronunciation_respelling_key "Help:Pronunciation respelling key") |
| [Specialty](https://en.wikipedia.org/wiki/Medical_specialty "Medical specialty") | [Psychiatry](https://en.wikipedia.org/wiki/Psychiatry "Psychiatry")[\[1\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-1) |
| [Symptoms](https://en.wikipedia.org/wiki/Signs_and_symptoms "Signs and symptoms") | [Hallucinations](https://en.wikipedia.org/wiki/Hallucination "Hallucination"), [delusions](https://en.wikipedia.org/wiki/Delusion "Delusion"), [disorganized thinking](https://en.wikipedia.org/wiki/Thought_disorder "Thought disorder") or behavior, [flat](https://en.wikipedia.org/wiki/Reduced_affect_display "Reduced affect display") or [inappropriate affect](https://en.wikipedia.org/wiki/Inappropriate_affect "Inappropriate affect")[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2)[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3) |
| [Complications](https://en.wikipedia.org/wiki/Complication_\(medicine\) "Complication (medicine)") | Harm to self or others, [social isolation](https://en.wikipedia.org/wiki/Social_isolation "Social isolation"), [heart disease](https://en.wikipedia.org/wiki/Cardiovascular_disease "Cardiovascular disease"), [suicide](https://en.wikipedia.org/wiki/Suicide "Suicide"), [lifestyle diseases](https://en.wikipedia.org/wiki/Lifestyle_disease "Lifestyle disease"),[\[4\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-SBU2012-4) [obesity](https://en.wikipedia.org/wiki/Obesity "Obesity") and [type 2 diabetes](https://en.wikipedia.org/wiki/Type_2_diabetes "Type 2 diabetes") arising from [antipsychotic](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic") medication[\[5\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-5)[\[6\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-6) |
| Usual onset | Ages 16 to 30[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3) |
| Duration | Chronic[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3) |
| [Causes](https://en.wikipedia.org/wiki/Cause_\(medicine\) "Cause (medicine)") | Environmental and genetic factors[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) |
| [Risk factors](https://en.wikipedia.org/wiki/Risk_factor "Risk factor") | [Family history](https://en.wikipedia.org/wiki/Family_history_\(medicine\) "Family history (medicine)"), [cannabis](https://en.wikipedia.org/wiki/Cannabis_\(drug\) "Cannabis (drug)") use in adolescence, [hallucinogen](https://en.wikipedia.org/wiki/Hallucinogen "Hallucinogen")\- or [amphetamine](https://en.wikipedia.org/wiki/Amphetamine "Amphetamine")\-associated psychosis,[\[8\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-8) problems during pregnancy, [childhood adversity](https://en.wikipedia.org/wiki/Adverse_childhood_experiences "Adverse childhood experiences"), being born or raised in a city[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)[\[9\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-9) |
| [Diagnostic method](https://en.wikipedia.org/wiki/Medical_diagnosis "Medical diagnosis") | Based on observed behavior, reported experiences, and reports of others familiar with the person[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) |
| [Differential diagnosis](https://en.wikipedia.org/wiki/Differential_diagnosis "Differential diagnosis") | [Substance use disorder](https://en.wikipedia.org/wiki/Substance_use_disorder "Substance use disorder"), [Huntington's disease](https://en.wikipedia.org/wiki/Huntington%27s_disease "Huntington's disease"), [mood disorders](https://en.wikipedia.org/wiki/Mood_disorders "Mood disorders") ([bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder"), [major depressive disorder](https://en.wikipedia.org/wiki/Major_depressive_disorder "Major depressive disorder")), [autism](https://en.wikipedia.org/wiki/Autism "Autism"),[\[11\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2010-11) [borderline personality disorder](https://en.wikipedia.org/wiki/Borderline_personality_disorder "Borderline personality disorder"),[\[12\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Paris2018-12) [schizophreniform disorder](https://en.wikipedia.org/wiki/Schizophreniform_disorder "Schizophreniform disorder"), [schizotypal personality disorder](https://en.wikipedia.org/wiki/Schizotypal_personality_disorder "Schizotypal personality disorder"), [schizoid personality disorder](https://en.wikipedia.org/wiki/Schizoid_personality_disorder "Schizoid personality disorder"), [antisocial personality disorder](https://en.wikipedia.org/wiki/Antisocial_personality_disorder "Antisocial personality disorder"), [psychotic depression](https://en.wikipedia.org/wiki/Psychotic_depression "Psychotic depression"), [anxiety](https://en.wikipedia.org/wiki/Anxiety "Anxiety"), [disruptive mood dysregulation disorder](https://en.wikipedia.org/wiki/Disruptive_mood_dysregulation_disorder "Disruptive mood dysregulation disorder"), [sleep paralysis](https://en.wikipedia.org/wiki/Sleep_paralysis "Sleep paralysis") |
| Management | Counseling, [life skills](https://en.wikipedia.org/wiki/Life_skills "Life skills") training[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2)[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) |
| [Medication](https://en.wikipedia.org/wiki/Medication "Medication") | [Antipsychotics](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic")[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) |
| [Prognosis](https://en.wikipedia.org/wiki/Prognosis "Prognosis") | 20–28 years shorter [life expectancy](https://en.wikipedia.org/wiki/Life_expectancy "Life expectancy")[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13)[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) |
| Frequency | ~0.32% (1 in 300) of the global population is affected[\[15\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO_FACT_SHEET-15) |
| Deaths | ~17,000 (2015)[\[16\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2015-16) |
**Schizophrenia** is a [mental disorder](https://en.wikipedia.org/wiki/Mental_disorder "Mental disorder")[\[17\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-17)[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) characterized variously by [hallucinations](https://en.wikipedia.org/wiki/Hallucination "Hallucination") (typically, [hearing voices](https://en.wikipedia.org/wiki/Auditory_hallucination#Schizophrenia "Auditory hallucination")), [delusions](https://en.wikipedia.org/wiki/Delusion "Delusion"), [disorganized thinking](https://en.wikipedia.org/wiki/Thought_disorder "Thought disorder") or behavior,[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) and [flat](https://en.wikipedia.org/wiki/Reduced_affect_display "Reduced affect display") or [inappropriate affect](https://en.wikipedia.org/wiki/Inappropriate_affect "Inappropriate affect").[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) Symptoms [develop gradually](https://en.wikipedia.org/wiki/Prodrome "Prodrome") and typically begin during young adulthood and rarely resolve.[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3)[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[18\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-18) There is no objective diagnostic test; diagnosis is based on observed behavior, a [psychiatric history](https://en.wikipedia.org/wiki/Psychiatric_history "Psychiatric history") that includes the person's reported experiences, and reports of others familiar with the person.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) For a [formal diagnosis](https://en.wikipedia.org/wiki/Diagnosis_of_schizophrenia "Diagnosis of schizophrenia"), the described symptoms need to have been present for at least six months (according to the [DSM-5](https://en.wikipedia.org/wiki/DSM-5 "DSM-5")) or one month (according to the [ICD-11](https://en.wikipedia.org/wiki/ICD-11 "ICD-11")).[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[19\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2019-19) Many people with schizophrenia have other mental disorders, especially [mood](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder"), [anxiety](https://en.wikipedia.org/wiki/Anxiety_disorder "Anxiety disorder"), and [substance use](https://en.wikipedia.org/wiki/Substance_use_disorder "Substance use disorder") disorders, as well as [obsessive–compulsive disorder](https://en.wikipedia.org/wiki/Obsessive%E2%80%93compulsive_disorder "Obsessive–compulsive disorder") (OCD).[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)
The [lifetime prevalence](https://en.wikipedia.org/wiki/Lifetime_prevalence "Lifetime prevalence") of developing schizophrenia is about 0.3% to 0.7%.[\[20\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Javitt2014-20) In 2017, there were an estimated 1.1 million new cases and in 2022 a total of 24 million cases globally.[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2)[\[21\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2018-21) Males are more often affected and on average have an earlier onset than females.[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2) The causes of schizophrenia may include [genetic](https://en.wikipedia.org/wiki/Heredity "Heredity") and [environmental](https://en.wikipedia.org/wiki/Environmental_factor "Environmental factor") factors.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) Genetic factors include a variety of common and rare [genetic variants](https://en.wikipedia.org/wiki/Human_genetic_variation "Human genetic variation").[\[22\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-vandeLeemput2016-22) Possible environmental factors include [being raised in a city](https://en.wikipedia.org/wiki/Risk_factors_of_schizophrenia#Urbanicity "Risk factors of schizophrenia"), childhood adversity, [cannabis](https://en.wikipedia.org/wiki/Cannabis_\(drug\) "Cannabis (drug)") use during adolescence, infections, the [age of a person's mother](https://en.wikipedia.org/wiki/Advanced_maternal_age "Advanced maternal age") or [father](https://en.wikipedia.org/wiki/Paternal_age_effect "Paternal age effect"), and poor [nutrition during pregnancy](https://en.wikipedia.org/wiki/Prenatal_nutrition "Prenatal nutrition").[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)[\[23\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Parakh2013-23)
About half of those diagnosed with schizophrenia will experience a marked improvement over the long term with no further relapses, and a small proportion of these will recover completely.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[24\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vita2018-24) The other half will have a lifelong impairment.[\[25\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Law2015-25) In severe cases, people may be admitted to hospitals.[\[24\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vita2018-24) Social problems such as [long-term unemployment](https://en.wikipedia.org/wiki/Long-term_unemployment "Long-term unemployment"), poverty, [homelessness](https://en.wikipedia.org/wiki/Homelessness "Homelessness"), exploitation, and victimization are commonly correlated with schizophrenia.[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26)[\[27\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Charleson2018-27) Compared to the general population, people with schizophrenia have a higher suicide rate (about 5% overall) and more [physical health problems](https://en.wikipedia.org/wiki/Physical_health_in_schizophrenia "Physical health in schizophrenia"),[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28)[\[29\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jop2010-29) leading to an average decrease in [life expectancy](https://en.wikipedia.org/wiki/Life_expectancy "Life expectancy") by 20[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13) to 28 years.[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) In 2015, an estimated 17,000 deaths were linked to schizophrenia.[\[16\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2015-16)
The mainstay of treatment is [antipsychotic](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic") medication, including [olanzapine](https://en.wikipedia.org/wiki/Olanzapine "Olanzapine") and [risperidone](https://en.wikipedia.org/wiki/Risperidone "Risperidone"), along with [counseling](https://en.wikipedia.org/wiki/Psychotherapy "Psychotherapy"), job training, and [social rehabilitation](https://en.wikipedia.org/wiki/Psychiatric_rehabilitation "Psychiatric rehabilitation").[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) Up to a third of people do not respond to initial antipsychotics, in which case [clozapine](https://en.wikipedia.org/wiki/Clozapine "Clozapine") is offered.[\[30\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Siskind2017-30) Most antipsychotics improve schizophrenia symptoms, with [clozapine](https://en.wikipedia.org/wiki/Clozapine "Clozapine") the most effective overall; side effects vary considerably and guide treatment choices.[\[31\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:3-31) In situations where doctors judge that there is a risk of harm to self or others, they may impose short [involuntary hospitalization](https://en.wikipedia.org/wiki/Involuntary_commitment "Involuntary commitment").[\[32\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BeckerKilian2006-32) Long-term hospitalization is used on a small number of people with severe schizophrenia.[\[33\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Capdevielle2009-33) In some countries where supportive services are limited or unavailable, long-term hospital stays are more common.[\[34\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Narayan2012-34)
## Signs and symptoms
Schizophrenia is a [mental disorder](https://en.wikipedia.org/wiki/Mental_disorder "Mental disorder") characterized by significant alterations in [perception](https://en.wikipedia.org/wiki/Perception "Perception"), thoughts, mood, and behavior.[\[35\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NICE2014-35) Symptoms are described in terms of positive, negative, and cognitive symptoms.[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3)[\[36\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-36) The positive symptoms of schizophrenia are the same for any [psychosis](https://en.wikipedia.org/wiki/Psychosis "Psychosis") and are sometimes referred to as psychotic symptoms. These may be present in any of the different psychoses and are often transient, making early diagnosis of schizophrenia problematic. Psychosis noted for the first time in a person who is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP).[\[37\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-RAISE-37)[\[38\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-38)
### Positive symptoms
[](https://en.wikipedia.org/wiki/File:Disorganized_Numbers.jpg)
Example of delusional obsession with numbers, disorganized thoughts, occurring with paranoid schizophrenia.
Positive symptoms are those that are not normally experienced, but are present in people during a psychotic episode in schizophrenia, including [delusions](https://en.wikipedia.org/wiki/Delusion "Delusion"), [hallucinations](https://en.wikipedia.org/wiki/Hallucination "Hallucination"), and disorganized thoughts, speech and behavior or inappropriate affect, typically regarded as manifestations of psychosis.[\[37\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-RAISE-37) Hallucinations occur at some point in the lifetimes of 80% of those with schizophrenia[\[39\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Montagnese2021-39) and most commonly involve the sense of [hearing](https://en.wikipedia.org/wiki/Hearing "Hearing") (most often [hearing voices](https://en.wikipedia.org/wiki/Auditory_verbal_hallucinations "Auditory verbal hallucinations")), but can sometimes involve any of the other [senses](https://en.wikipedia.org/wiki/Sense "Sense") such as [taste](https://en.wikipedia.org/wiki/Taste "Taste"), [sight](https://en.wikipedia.org/wiki/Visual_perception "Visual perception"), [smell](https://en.wikipedia.org/wiki/Olfaction "Olfaction"), and [touch](https://en.wikipedia.org/wiki/Tactile_hallucination "Tactile hallucination").[\[40\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-40) The frequency of hallucinations involving multiple senses is double the rate of those involving only one sense.[\[39\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Montagnese2021-39) They are also typically related to the content of the delusional theme.[\[41\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSMIV-41) [Delusions](https://en.wikipedia.org/wiki/Delusion "Delusion") are [bizarre](https://en.wikipedia.org/wiki/Delusion#Types "Delusion") or [persecutory](https://en.wikipedia.org/wiki/Persecutory_delusions "Persecutory delusions") in nature. [Distortions of self-experience](https://en.wikipedia.org/wiki/Self-disorder "Self-disorder") such as feeling that [others can hear one's thoughts](https://en.wikipedia.org/wiki/Thought_broadcasting "Thought broadcasting") (thought broadcasting delusion) or that [thoughts are being inserted into one's mind](https://en.wikipedia.org/wiki/Thought_insertion "Thought insertion"), sometimes termed passivity phenomena, are also common.[\[42\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Heinz2016-42)[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3) The type and content of auditory and visual hallucinations appears to be influenced, at least in part, by cultural and religious factors. Patients in the United Kingdom and United States are more likely to report hearing criticisms and commands; patients in Africa, Asia, and the Middle East report more religious messaging in their hallucinations. This is true even among transplants to these countries, suggesting these differences are cultural, and not genetic.\[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed "Wikipedia:Citation needed")*\] Positive symptoms generally respond well to medication[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) and become reduced over the course of the illness, perhaps linked to the age-related decline in dopamine activity.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)
### Negative symptoms
Negative symptoms are deficits of normal emotional responses, or of other thought processes. The five recognized domains of negative symptoms are: [blunted affect](https://en.wikipedia.org/wiki/Blunted_affect "Blunted affect") – showing flat expressions (monotone) or little emotion; [alogia](https://en.wikipedia.org/wiki/Alogia "Alogia") – a poverty of speech; [anhedonia](https://en.wikipedia.org/wiki/Anhedonia "Anhedonia") – an inability to feel pleasure; [asociality](https://en.wikipedia.org/wiki/Asociality "Asociality") – the lack of desire to form relationships, and [avolition](https://en.wikipedia.org/wiki/Avolition "Avolition") – a lack of motivation and [apathy](https://en.wikipedia.org/wiki/Apathy "Apathy").[\[43\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Adida2015-43)[\[44\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-44) Avolition and anhedonia are seen as motivational deficits resulting from impaired reward processing.[\[45\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-45)[\[46\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Husain2018-46) Reward is the main driver of motivation and this is mostly mediated by dopamine.[\[46\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Husain2018-46) It has been suggested that negative symptoms are multidimensional and they have been categorised into two subdomains of apathy or lack of motivation, and diminished expression.[\[43\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Adida2015-43)[\[47\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Galderisi2018-47) Apathy includes avolition, anhedonia, and social withdrawal; diminished expression includes blunt affect and alogia.[\[48\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-48) Sometimes diminished expression is treated as both verbal and non-verbal.[\[49\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-49)
Apathy accounts for around 50% of the most often found negative symptoms and affects functional outcome and subsequent quality of life. Apathy is related to disrupted cognitive processing affecting memory and planning, including goal-directed behaviour.[\[50\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-50) The two subdomains have suggested a need for separate treatment approaches.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51) A lack of distress is another noted negative symptom.[\[52\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Tatsumi2020-52) A distinction is often made between those negative symptoms that are inherent to schizophrenia, termed primary; and those that result from positive symptoms, from the side effects of antipsychotics, substance use disorder, and social deprivation, termed secondary negative symptoms.[\[53\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-53) Negative symptoms are less responsive to medication and the most difficult to treat.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51) However, if properly assessed, secondary negative symptoms are amenable to treatment.[\[47\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Galderisi2018-47) There is some evidence that the negative symptoms of schizophrenia are amenable to psychostimulant medication, although such drugs have varying degrees of risk for causing positive psychotic symptoms.[\[54\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lindenmayer_Nasrallah_Pucci_systematic_review-54)
Scales for specifically assessing the presence of negative symptoms, and for measuring their severity, and their changes have been introduced since the earlier scales such as the [PANSS](https://en.wikipedia.org/wiki/Positive_and_Negative_Syndrome_Scale "Positive and Negative Syndrome Scale") that deals with all types of symptoms.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51) These scales are the *Clinical Assessment Interview for Negative Symptoms* (CAINS), and the *Brief Negative Symptom Scale* (BNSS) also known as second-generation scales.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51)[\[52\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Tatsumi2020-52)[\[55\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-55) In 2020, ten years after its introduction, a cross-cultural study of the use of BNSS found valid and reliable [psychometric](https://en.wikipedia.org/wiki/Psychometric "Psychometric") evidence for its five-domain structure cross-culturally. The BNSS can assess both the presence and severity of negative symptoms of the five recognized domains and an additional item of reduced normal distress. It has been used to measure changes in negative symptoms in trials of psychosocial and pharmacological interventions.[\[52\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Tatsumi2020-52)
### Cognitive symptoms
See also: [Visual processing abnormalities in schizophrenia](https://en.wikipedia.org/wiki/Visual_processing_abnormalities_in_schizophrenia "Visual processing abnormalities in schizophrenia")
[](https://en.wikipedia.org/wiki/File:SchizophreniaBrain.jpg)
Map of deficits in [neural tissue](https://en.wikipedia.org/wiki/Neural_tissue "Neural tissue") throughout the human brain in a patient with schizophrenia. The most deficient areas are magenta, while the least deficient areas are blue.
[](https://en.wikipedia.org/wiki/File:Schizophrenia_brain_large.gif)
Diagram of the brain in schizophrenia
An estimated 70% of those with schizophrenia have cognitive deficits, and these are most pronounced in early-onset and late-onset illness.[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56)[\[57\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kar2016-57) These are often evident long before the onset of illness in the [prodromal stage](https://en.wikipedia.org/wiki/Prodromal_schizophrenia "Prodromal schizophrenia"), and may be present in childhood or early adolescence.[\[58\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Bozikas2011-58)[\[59\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-59) They are core features but not considered core symptoms, as are positive and negative symptoms.[\[60\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Biedermann2016-60)[\[61\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vidailhet2013-61) However, their presence and degree of dysfunction are taken as better indicators of functionality than the presentation of core symptoms.[\[58\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Bozikas2011-58) Cognitive deficits become worse at first episode psychosis but then return to baseline, and remain fairly stable over the course of the illness.[\[62\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Hashimoto2019-62)[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63)
Cognitive deficits may be of [neurocognition](https://en.wikipedia.org/wiki/Neurocognition "Neurocognition") (nonsocial) or of [social cognition](https://en.wikipedia.org/wiki/Social_cognition "Social cognition").[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) Neurocognition is the ability to receive and remember information, and includes verbal fluency, [memory](https://en.wikipedia.org/wiki/Memory "Memory"), [reasoning](https://en.wikipedia.org/wiki/Reason "Reason"), [problem solving](https://en.wikipedia.org/wiki/Problem_solving "Problem solving"), [speed of processing](https://en.wikipedia.org/wiki/Information_processing_\(psychology\) "Information processing (psychology)"), and [auditory](https://en.wikipedia.org/wiki/Auditory_system "Auditory system") and visual perception.[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63) [Verbal memory](https://en.wikipedia.org/wiki/Verbal_memory "Verbal memory") and attention are seen to be the most affected.[\[64\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Megreya2016-64)[\[65\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-65) Verbal memory impairment is associated with a decreased level of [semantic processing](https://en.wikipedia.org/wiki/Semantic_processing "Semantic processing") (relating meaning to words).[\[66\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-66) Another memory impairment is that of [episodic memory](https://en.wikipedia.org/wiki/Episodic_memory "Episodic memory").[\[67\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-67) An impairment in visual perception that is consistently found in schizophrenia is that of [visual backward masking](https://en.wikipedia.org/wiki/Visual_backward_masking "Visual backward masking").[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63) [Visual processing](https://en.wikipedia.org/wiki/Visual_processing "Visual processing") impairments include an inability to perceive complex [visual illusions](https://en.wikipedia.org/wiki/Visual_illusion "Visual illusion").[\[68\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-68) Social cognition is concerned with the mental operations needed to interpret, and understand the self and others in the social world.[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63)[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) This is also an associated impairment, and [facial emotion perception](https://en.wikipedia.org/wiki/Face_perception#Schizophrenia "Face perception") is often found to be difficult.[\[69\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-69)[\[70\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-70) Cognitive impairments do not usually respond to antipsychotics, and there are a number of [interventions](https://en.wikipedia.org/wiki/Schizophrenia#Psychosocial_interventions) that are used to try to improve them; [cognitive remediation therapy](https://en.wikipedia.org/wiki/Cognitive_remediation_therapy "Cognitive remediation therapy") is of particular help.[\[61\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vidailhet2013-61)
[Neurological soft signs](https://en.wikipedia.org/wiki/Neurological_soft_signs "Neurological soft signs") of clumsiness and loss of fine motor movement are often found in schizophrenia, which may resolve with effective treatment of FEP.[\[19\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2019-19)[\[71\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-71)
### Onset
Further information: [Basic symptoms of schizophrenia](https://en.wikipedia.org/wiki/Basic_symptoms_of_schizophrenia "Basic symptoms of schizophrenia")
See also: [Childhood schizophrenia](https://en.wikipedia.org/wiki/Childhood_schizophrenia "Childhood schizophrenia") and [Adolescence § Changes in the brain](https://en.wikipedia.org/wiki/Adolescence#Changes_in_the_brain "Adolescence")
Onset typically occurs between the late teens and early 30s, with the peak incidence occurring in males in the early to mid-twenties, and in females in the late twenties.[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3)[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[19\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2019-19) Onset before the age of 17 is known as early-onset,[\[72\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-72) and before the age of 13, as can sometimes occur, is known as [childhood schizophrenia](https://en.wikipedia.org/wiki/Childhood_schizophrenia "Childhood schizophrenia") or very early-onset.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[73\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DaFonseca2018-73) Onset can occur between the ages of 40 and 60, known as late-onset schizophrenia.[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) Onset over the age of 60, which may be difficult to differentiate as schizophrenia, is known as very-late-onset schizophrenia-like psychosis.[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) Late onset has shown that a higher rate of females are affected; they have less severe symptoms and need lower doses of antipsychotics.[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) The tendency for earlier onset in males is later seen to be balanced by a [post-menopausal](https://en.wikipedia.org/wiki/Post-menopausal "Post-menopausal") increase in the development in females. [Estrogen](https://en.wikipedia.org/wiki/Estrogen "Estrogen") produced pre-menopause has a dampening effect on dopamine receptors but its protection can be overridden by a genetic overload.[\[74\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-74) There has been a dramatic increase in the numbers of older adults with schizophrenia.[\[75\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-75)
Onset may happen suddenly or may occur after the slow and gradual development of a number of signs and symptoms, a period known as the [prodromal stage](https://en.wikipedia.org/wiki/Prodromal_schizophrenia "Prodromal schizophrenia").[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) Up to 75% of those with schizophrenia go through a prodromal stage.[\[76\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-George2017-76) The negative and cognitive symptoms in the prodrome stage can precede FEP (first episode psychosis) by many months and up to five years.[\[62\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Hashimoto2019-62)[\[77\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Conroy2018-77) The period from FEP and treatment is known as the duration of untreated psychosis (DUP) which is seen to be a factor in functional outcome. The prodromal stage is the high-risk stage for the development of psychosis.[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63) Since the progression to first episode psychosis is not inevitable, an alternative term is often preferred of [at risk mental state](https://en.wikipedia.org/wiki/At_risk_mental_state "At risk mental state").[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63) Cognitive dysfunction at an early age impacts a young person's usual cognitive development.[\[78\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-78) Recognition and early intervention at the prodromal stage would minimize the associated disruption to educational and social development and has been the focus of many studies.[\[62\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Hashimoto2019-62)[\[77\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Conroy2018-77)
## Risk factors
Main article: [Risk factors of schizophrenia](https://en.wikipedia.org/wiki/Risk_factors_of_schizophrenia "Risk factors of schizophrenia")
Schizophrenia is described as a [neurodevelopmental disorder](https://en.wikipedia.org/wiki/Neurodevelopmental_disorder "Neurodevelopmental disorder") with no precise boundary, or single cause, and is thought to develop from [gene–environment interactions](https://en.wikipedia.org/wiki/Gene%E2%80%93environment_interaction "Gene–environment interaction") with involved vulnerability factors.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)[\[79\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-79)[\[80\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Davis2016-80) The interactions of these [risk factors](https://en.wikipedia.org/wiki/Risk_factor_\(epidemiology\) "Risk factor (epidemiology)") are complex, as numerous and diverse [insults](https://en.wikipedia.org/wiki/Insult_\(medical\) "Insult (medical)") from conception to adulthood can be involved.[\[80\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Davis2016-80) A genetic predisposition on its own, without interacting environmental factors, will not give rise to the development of schizophrenia.[\[80\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Davis2016-80)[\[81\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Perkovic2017-81) The genetic component means that [prenatal](https://en.wikipedia.org/wiki/Prenatal_development "Prenatal development") brain development is disturbed, and environmental influence affects the postnatal development of the brain.[\[82\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Suvisaari2010-82) Evidence suggests that genetically susceptible children are more likely to be vulnerable to the effects of environmental risk factors.[\[82\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Suvisaari2010-82)
### Genetic
Estimates of the [heritability](https://en.wikipedia.org/wiki/Heritability "Heritability") of schizophrenia are between 70% and 80%, which implies that 70% to 80% of the individual differences in risk of schizophrenia are associated with genetics.[\[22\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-vandeLeemput2016-22)[\[83\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Her2011-83) These estimates vary because of the [difficulty in separating](https://en.wikipedia.org/wiki/Behavioural_genetics "Behavioural genetics") genetic and environmental influences, and their accuracy has been queried.[\[84\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-84)[\[85\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Torrey2019-85) The greatest risk factor for developing schizophrenia is having a [first-degree relative](https://en.wikipedia.org/wiki/First-degree_relative "First-degree relative") with the disease (risk is 6.5%); more than 40% of [identical twins](https://en.wikipedia.org/wiki/Twin#Monozygotic_\(identical\)_twins "Twin") of those with schizophrenia are also affected.[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86) If one parent is affected the risk is about 13% and if both are affected the risk is nearly 50%.[\[83\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Her2011-83) However, the *DSM-5* indicates that most people with schizophrenia have no family history of psychosis.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) Results of [candidate gene](https://en.wikipedia.org/wiki/Candidate_gene "Candidate gene") studies of schizophrenia have generally failed to find consistent associations,[\[87\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-87) and the [genetic loci](https://en.wikipedia.org/wiki/Genetic_loci "Genetic loci") identified by [genome-wide association studies](https://en.wikipedia.org/wiki/Genome-wide_association_studies "Genome-wide association studies") explain only a small fraction of the variation in the disease.[\[88\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-88)
Many [genes](https://en.wikipedia.org/wiki/Genes "Genes") are known to be involved in schizophrenia, each with small effects and unknown [transmission](https://en.wikipedia.org/wiki/Gene#Molecular_inheritance "Gene") and [expression](https://en.wikipedia.org/wiki/Gene_expression "Gene expression").[\[22\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-vandeLeemput2016-22)[\[89\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-89)[\[90\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-90) The summation of these effect sizes into a [polygenic risk score](https://en.wikipedia.org/wiki/Polygenic_score "Polygenic score") can explain at least 7% of the variability in liability for schizophrenia.[\[91\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-91) Around 5% of cases of schizophrenia are understood to be at least partially attributable to rare [copy number variations](https://en.wikipedia.org/wiki/Copy_number_variation "Copy number variation") (CNVs); these [structural variations](https://en.wikipedia.org/wiki/Structural_variation "Structural variation") are associated with known genomic disorders involving [deletions](https://en.wikipedia.org/wiki/Deletion_\(genetics\) "Deletion (genetics)") at [22q11.2](https://en.wikipedia.org/wiki/Chromosome_22#Chromosomal_conditions "Chromosome 22") ([DiGeorge syndrome](https://en.wikipedia.org/wiki/DiGeorge_syndrome "DiGeorge syndrome")) and [17q12](https://en.wikipedia.org/wiki/Chromosome_17#Diseases_and_disorders "Chromosome 17") ([17q12 microdeletion syndrome](https://en.wikipedia.org/wiki/17q12_microdeletion_syndrome "17q12 microdeletion syndrome")), duplications at [16p11.2](https://en.wikipedia.org/wiki/Chromosome_16#Cytogenetic_band "Chromosome 16") (most frequently found) and deletions at [15q11.2](https://en.wikipedia.org/wiki/Chromosome_15#Cytogenetic_band "Chromosome 15") ([Burnside–Butler syndrome](https://en.wikipedia.org/wiki/Burnside%E2%80%93Butler_syndrome "Burnside–Butler syndrome")).[\[92\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lowther2017p82-92) Some of these CNVs increase the risk of developing schizophrenia by as much as 20-fold, and are frequently comorbid with autism and intellectual disabilities.[\[92\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lowther2017p82-92)
The genes [CRHR1](https://en.wikipedia.org/wiki/CRHR1 "CRHR1") and [CRHBP](https://en.wikipedia.org/wiki/CRHBP "CRHBP") are associated with the severity of suicidal behavior. These genes code for stress response proteins needed in the control of the [HPA axis](https://en.wikipedia.org/wiki/HPA_axis "HPA axis"), and their interaction can affect this axis. Response to stress can cause lasting changes in the [function of the HPA axis](https://en.wikipedia.org/wiki/HPA_axis#Stress_and_development "HPA axis") possibly disrupting the negative feedback mechanism, [homeostasis](https://en.wikipedia.org/wiki/Homeostasis "Homeostasis"), and the regulation of emotion leading to altered behaviors.[\[81\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Perkovic2017-81)
The question of how schizophrenia could be primarily genetically influenced, given that people with schizophrenia have lower fertility rates, is a paradox. It is expected that [genetic variants](https://en.wikipedia.org/wiki/Allele "Allele") that increase the risk of schizophrenia would be selected against, due to their negative effects on [reproductive fitness](https://en.wikipedia.org/wiki/Reproductive_fitness "Reproductive fitness"). A number of potential explanations have been proposed, including that [alleles](https://en.wikipedia.org/wiki/Allele "Allele") associated with schizophrenia risk confers a fitness advantage in unaffected individuals.[\[93\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-93)[\[94\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-94) While some evidence has not supported this idea,[\[85\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Torrey2019-85) others propose that a large number of alleles each contributing a small amount can persist.[\[95\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-95)
A meta-analysis found that oxidative [DNA damage](https://en.wikipedia.org/wiki/DNA_damage_\(naturally_occurring\) "DNA damage (naturally occurring)") was significantly increased in schizophrenia.[\[96\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Goh2021-96)
### Environmental
Further information: [Prenatal nutrition](https://en.wikipedia.org/wiki/Prenatal_nutrition "Prenatal nutrition"), [Prenatal stress](https://en.wikipedia.org/wiki/Prenatal_stress "Prenatal stress"), and [Neuroplastic effects of pollution](https://en.wikipedia.org/wiki/Neuroplastic_effects_of_pollution "Neuroplastic effects of pollution")
Environmental factors, each associated with a slight risk of developing schizophrenia in later life include [oxygen deprivation](https://en.wikipedia.org/wiki/Intrauterine_hypoxia "Intrauterine hypoxia"), infection, [prenatal maternal stress](https://en.wikipedia.org/wiki/Prenatal_maternal_stress "Prenatal maternal stress"), and malnutrition in the mother during prenatal development.[\[97\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Stilo2019-97) A risk is associated with maternal obesity, in increasing [oxidative stress](https://en.wikipedia.org/wiki/Oxidative_stress "Oxidative stress"), and dysregulating the dopamine and serotonin pathways.[\[98\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-98) Both maternal stress and infection have been demonstrated to alter fetal [neurodevelopment](https://en.wikipedia.org/wiki/Neurodevelopment "Neurodevelopment") through an increase of pro-inflammatory [cytokines](https://en.wikipedia.org/wiki/Cytokine "Cytokine").[\[99\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Upthegrove2020-99) There is a slighter risk associated with being born in the winter or spring possibly due to [vitamin D deficiency](https://en.wikipedia.org/wiki/Vitamin_D_deficiency "Vitamin D deficiency")[\[100\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Chiang2016-100) or a prenatal [viral infection](https://en.wikipedia.org/wiki/Viral_infection "Viral infection").[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86) Other infections during pregnancy or around the time of birth that have been linked to an increased risk include infections by *[Toxoplasma gondii](https://en.wikipedia.org/wiki/Toxoplasma_gondii "Toxoplasma gondii")* and *[Chlamydia](https://en.wikipedia.org/wiki/Chlamydia_infection "Chlamydia infection")*.[\[101\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-101) The increased risk is about five to eight percent.[\[102\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-yolken-102) Viral infections of the brain during childhood are also linked to a risk of schizophrenia during adulthood.[\[103\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-103) [Cat exposure](https://en.wikipedia.org/wiki/Human_interaction_with_cats "Human interaction with cats") is also associated with an increased risk of broadly defined schizophrenia-related disorders, with an [odds ratio](https://en.wikipedia.org/wiki/Odds_ratio "Odds ratio") of 2.4.[\[104\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-104) Exposure to specific medications such as [tramadol](https://en.wikipedia.org/wiki/Tramadol "Tramadol") and [desmopressin](https://en.wikipedia.org/wiki/Desmopressin "Desmopressin") has been found be associated with an increased risk of incident schizophrenia, while other medications including [anti-protozoans](https://en.wikipedia.org/wiki/Antiprotozoal "Antiprotozoal") were associated with a decrease in schizophrenia risk.[\[105\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-105)
[Adverse childhood experiences](https://en.wikipedia.org/wiki/Adverse_childhood_experiences "Adverse childhood experiences") (ACEs), severe forms of which are classed as [childhood trauma](https://en.wikipedia.org/wiki/Childhood_trauma "Childhood trauma"), range from being bullied or abused, to the death of a parent.[\[106\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pearce2019-106) Many adverse childhood experiences can cause [toxic stress](https://en.wikipedia.org/wiki/Toxic_stress "Toxic stress") and increase the risk of psychosis.[\[106\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pearce2019-106)[\[107\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-107)[\[108\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-108) Chronic trauma, including ACEs, can promote lasting inflammatory dysregulation throughout the nervous system.[\[109\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Nettis2020-109) It is suggested that early stress may contribute to the development of schizophrenia through these alterations in the immune system.[\[109\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Nettis2020-109) Schizophrenia was the last diagnosis to benefit from the link made between ACEs and adult mental health outcomes.[\[110\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-110)
Living in an [urban environment](https://en.wikipedia.org/wiki/Risk_factors_of_schizophrenia#Urbanicity "Risk factors of schizophrenia") during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two,[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28)[\[111\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-111) even after taking into account [drug use](https://en.wikipedia.org/wiki/Recreational_drug_use "Recreational drug use"), [ethnic group](https://en.wikipedia.org/wiki/Ethnic_group "Ethnic group"), and size of [social group](https://en.wikipedia.org/wiki/Social_group "Social group").[\[112\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-112) A possible link between the [urban environment and pollution](https://en.wikipedia.org/wiki/Neuroplastic_effects_of_pollution "Neuroplastic effects of pollution") has been suggested to be the cause of the elevated risk of schizophrenia.[\[113\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-113) Other risk factors include [social isolation](https://en.wikipedia.org/wiki/Social_isolation "Social isolation"), immigration related to social adversity and racial discrimination, family dysfunction, unemployment, and poor housing conditions.[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)[\[114\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-114)[\[115\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-115) Having a [father older than 40 years](https://en.wikipedia.org/wiki/Paternal_age_effect "Paternal age effect"), or parents younger than 20 years are also associated with schizophrenia.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)[\[116\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-116)
#### Substance use
Further information: [Risk factors of schizophrenia § Substance use](https://en.wikipedia.org/wiki/Risk_factors_of_schizophrenia#Substance_use "Risk factors of schizophrenia"), and [Substance-induced psychosis](https://en.wikipedia.org/wiki/Substance-induced_psychosis "Substance-induced psychosis")
About half of those with schizophrenia use [recreational drugs](https://en.wikipedia.org/wiki/Recreational_drugs "Recreational drugs") including [alcohol](https://en.wikipedia.org/wiki/Alcohol_\(drug\) "Alcohol (drug)"), tobacco, and [cannabis](https://en.wikipedia.org/wiki/Cannabis_\(drug\) "Cannabis (drug)") excessively.[\[117\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Gregg2007-117)[\[118\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-118) Use of [stimulants](https://en.wikipedia.org/wiki/Stimulant "Stimulant") such as [amphetamine](https://en.wikipedia.org/wiki/Amphetamine "Amphetamine") and [cocaine](https://en.wikipedia.org/wiki/Cocaine "Cocaine") can lead to a temporary [stimulant psychosis](https://en.wikipedia.org/wiki/Stimulant_psychosis "Stimulant psychosis"), which presents very similarly to schizophrenia.[\[119\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-119) Rarely, alcohol use can also result in a similar [alcohol-related psychosis](https://en.wikipedia.org/wiki/Alcoholic_hallucinosis "Alcoholic hallucinosis").[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)[\[120\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-alcohol-120) Drugs may also be used as coping mechanisms by people who have schizophrenia, to deal with depression, [anxiety](https://en.wikipedia.org/wiki/Anxiety "Anxiety"), boredom, and [loneliness](https://en.wikipedia.org/wiki/Loneliness "Loneliness").[\[117\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Gregg2007-117)[\[121\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Leweke08-121) The use of cannabis and tobacco are not associated with the development of cognitive deficits, and sometimes a reverse relationship is found where their use improves these symptoms.[\[61\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vidailhet2013-61) However, [substance use disorders](https://en.wikipedia.org/wiki/Substance_use_disorder "Substance use disorder") are associated with an increased risk of suicide, and a poor response to treatment.[\[122\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Khokhar2018-122)[\[123\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-123)
[Cannabis use](https://en.wikipedia.org/wiki/Long-term_effects_of_cannabis#Chronic_psychosis_and_schizophrenia_spectrum_disorders "Long-term effects of cannabis") may be a contributory factor in the development of schizophrenia, potentially increasing the risk of the disease in those who are already at risk.[\[124\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Patel2020-124)[\[125\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Hasan2020-125)[\[126\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-126) The increased risk may require the presence of certain genes within an individual.[\[23\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Parakh2013-23) Its use is associated with doubling the rate.[\[127\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-127)
## Causes
Main article: [Causes of schizophrenia](https://en.wikipedia.org/wiki/Causes_of_schizophrenia "Causes of schizophrenia")
See also: [Aberrant salience](https://en.wikipedia.org/wiki/Aberrant_salience "Aberrant salience")
The causes of schizophrenia are still unknown. Several models have been put forward to explain the link between altered brain function and schizophrenia.[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28) The prevailing model of schizophrenia is that of a [neurodevelopmental disorder](https://en.wikipedia.org/wiki/Neurodevelopmental_disorder "Neurodevelopmental disorder"), and the underlying changes that occur before symptoms become evident are seen as arising from the [interaction between genes and the environment](https://en.wikipedia.org/wiki/Gene-environment_interaction "Gene-environment interaction").[\[128\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-128) Extensive studies support this model.[\[76\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-George2017-76) Maternal infections, [malnutrition](https://en.wikipedia.org/wiki/Malnutrition "Malnutrition") and [complications during pregnancy](https://en.wikipedia.org/wiki/Complications_of_pregnancy "Complications of pregnancy") and [childbirth](https://en.wikipedia.org/wiki/Obstetric_labor_complication "Obstetric labor complication") are known risk factors for the development of schizophrenia, which usually emerges between the ages of 18 and 25, a period that overlaps with certain stages of neurodevelopment.[\[129\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-129) Gene-environment interactions lead to deficits in the [neural circuitry](https://en.wikipedia.org/wiki/Neural_circuit "Neural circuit") that affect sensory and cognitive functions.[\[76\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-George2017-76)
The common dopamine and glutamate models proposed are not mutually exclusive; each is seen to have a role in the neurobiology of schizophrenia.[\[130\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-130) The most common model put forward was the [dopamine hypothesis of schizophrenia](https://en.wikipedia.org/wiki/Dopamine_hypothesis_of_schizophrenia "Dopamine hypothesis of schizophrenia"), which attributes psychosis to the mind's faulty interpretation of the misfiring of [dopaminergic neurons](https://en.wikipedia.org/wiki/Dopaminergic_pathways "Dopaminergic pathways").[\[131\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-131) This has been directly related to the symptoms of delusions and hallucinations.[\[132\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-132)[\[133\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2014-133)[\[134\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-134) Abnormal dopamine signaling has been implicated in schizophrenia based on the usefulness of medications that affect the dopamine receptor and the observation that dopamine levels are increased during acute psychosis.[\[135\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-135)[\[136\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-136) A decrease in [D1 receptors](https://en.wikipedia.org/wiki/Dopamine_receptor_D1 "Dopamine receptor D1") in the [dorsolateral prefrontal cortex](https://en.wikipedia.org/wiki/Dorsolateral_prefrontal_cortex "Dorsolateral prefrontal cortex") may also be responsible for deficits in [working memory](https://en.wikipedia.org/wiki/Working_memory "Working memory").[\[137\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-137)[\[138\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-138)
The [glutamate hypothesis of schizophrenia](https://en.wikipedia.org/wiki/Glutamate_hypothesis_of_schizophrenia "Glutamate hypothesis of schizophrenia") links alterations between [glutamatergic neurotransmission](https://en.wikipedia.org/wiki/Glutamatergic_neurotransmission "Glutamatergic neurotransmission") and the [neural oscillations](https://en.wikipedia.org/wiki/Neural_oscillation "Neural oscillation") that affect [connections between the thalamus and the cortex](https://en.wikipedia.org/wiki/Thalamocortical_radiations "Thalamocortical radiations").[\[139\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pratt2017-139) Studies have shown that a reduced expression of a [glutamate receptor](https://en.wikipedia.org/wiki/Glutamate_receptor "Glutamate receptor") – [NMDA receptor](https://en.wikipedia.org/wiki/NMDA_receptor "NMDA receptor"), and glutamate blocking drugs such as [phencyclidine](https://en.wikipedia.org/wiki/Phencyclidine "Phencyclidine") and [ketamine](https://en.wikipedia.org/wiki/Ketamine "Ketamine") can mimic the symptoms and cognitive problems associated with schizophrenia.[\[139\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pratt2017-139)[\[140\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-140)[\[141\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-141) Post-mortem studies consistently find that a subset of these neurons fail to express [GAD67](https://en.wikipedia.org/wiki/Glutamate_decarboxylase#Schizophrenia_and_bipolar_disorder "Glutamate decarboxylase") ([GAD1](https://en.wikipedia.org/wiki/GAD1 "GAD1")),[\[142\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marin2012-142) in addition to abnormalities in [brain morphometry](https://en.wikipedia.org/wiki/Brain_morphometry "Brain morphometry"). The subsets of interneurons that are abnormal in schizophrenia are responsible for the synchronizing of neural ensembles needed during working memory tasks. These give the neural oscillations produced as [gamma waves](https://en.wikipedia.org/wiki/Gamma_wave "Gamma wave") that have a frequency of between 30 and 80 [hertz](https://en.wikipedia.org/wiki/Hertz "Hertz"). Both working memory tasks and gamma waves are impaired in schizophrenia, which may reflect abnormal interneuron functionality.[\[142\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marin2012-142)[\[143\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-143)[\[144\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-144)[\[145\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-145) An important process that may be disrupted in neurodevelopment is astrogenesis – the formation of [astrocytes](https://en.wikipedia.org/wiki/Astrocyte "Astrocyte"). Astrocytes are crucial in contributing to the formation and maintenance of neural circuits and it is believed that disruption in this role can result in a number of neurodevelopmental disorders including schizophrenia.[\[146\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Sloan2014-146) Evidence suggests that reduced numbers of astrocytes in deeper cortical layers are assocociated with a diminished expression of [EAAT2](https://en.wikipedia.org/wiki/EAAT2 "EAAT2"), a [glutamate transporter](https://en.wikipedia.org/wiki/Glutamate_transporter "Glutamate transporter") in astrocytes; supporting the glutamate hypothesis.[\[146\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Sloan2014-146)
Deficits in [executive functions](https://en.wikipedia.org/wiki/Executive_function "Executive function"), such as [planning](https://en.wikipedia.org/wiki/Planning "Planning"), [inhibition](https://en.wikipedia.org/wiki/Social_inhibition "Social inhibition"), and [working memory](https://en.wikipedia.org/wiki/Working_memory "Working memory"), are pervasive in schizophrenia. Although these functions are separable, their dysfunction in schizophrenia may reflect an underlying deficit in the ability to represent goal related information in working memory, and to use this to direct cognition and behavior.[\[147\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-147)[\[148\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-148) These impairments have been linked to a number of [neuroimaging](https://en.wikipedia.org/wiki/Neuroimaging "Neuroimaging") and [neuropathological abnormalities](https://en.wikipedia.org/w/index.php?title=Neuropathological_abnormalities&action=edit&redlink=1 "Neuropathological abnormalities (page does not exist)"). For example, functional neuroimaging studies report evidence of reduced neural processing efficiency, whereby the [dorsolateral prefrontal cortex](https://en.wikipedia.org/wiki/Dorsolateral_prefrontal_cortex "Dorsolateral prefrontal cortex") is activated to a greater degree to achieve a certain level of performance relative to controls on working memory tasks. These abnormalities may be linked to the consistent post-mortem finding of reduced [neuropil](https://en.wikipedia.org/wiki/Neuropil "Neuropil"), evidenced by increased [pyramidal cell](https://en.wikipedia.org/wiki/Pyramidal_cell "Pyramidal cell") density and reduced [dendritic spine](https://en.wikipedia.org/wiki/Dendritic_spine "Dendritic spine") density. These cellular and functional abnormalities may also be reflected in structural neuroimaging studies that find reduced [grey matter](https://en.wikipedia.org/wiki/Grey_matter "Grey matter") volume in association with deficits in working memory tasks.[\[149\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-149)
Positive symptoms have been linked to cortical thinning in the [superior temporal gyrus](https://en.wikipedia.org/wiki/Superior_temporal_gyrus "Superior temporal gyrus").[\[150\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-150) The severity of negative symptoms has been linked to reduced thickness in the left medial [orbitofrontal cortex](https://en.wikipedia.org/wiki/Orbitofrontal_cortex "Orbitofrontal cortex").[\[151\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-151) Anhedonia, traditionally defined as a reduced capacity to experience [pleasure](https://en.wikipedia.org/wiki/Pleasure "Pleasure"), is frequently reported in schizophrenia. However, a large body of evidence suggests that [hedonic responses](https://en.wikipedia.org/wiki/Hedonism "Hedonism") are intact in schizophrenia,[\[152\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-152) and that what is reported to be [anhedonia](https://en.wikipedia.org/wiki/Anhedonia "Anhedonia") is a reflection of dysfunction in other processes related to reward.[\[153\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-153) Overall, a failure of reward prediction is thought to lead to impairment in the generation of cognition and behavior required to obtain rewards, despite normal hedonic responses.[\[154\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-154)
Another theory links abnormal [brain lateralization](https://en.wikipedia.org/wiki/Lateralization_of_brain_function "Lateralization of brain function") to the development of [being left-handed](https://en.wikipedia.org/wiki/Handedness "Handedness") which is significantly more common in those with schizophrenia.[\[155\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Wilberg2019-155) This abnormal development of hemispheric asymmetry is noted in schizophrenia.[\[156\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-156) Studies have concluded that the link is a true and verifiable effect that may reflect a genetic link between lateralization and schizophrenia.[\[155\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Wilberg2019-155)[\[157\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-157)
[Bayesian models of brain functioning](https://en.wikipedia.org/wiki/Bayesian_approaches_to_brain_function "Bayesian approaches to brain function") have been used to link abnormalities in cellular functioning to symptoms.[\[158\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-158)[\[159\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-159) Both hallucinations and delusions have been suggested to reflect improper encoding of [prior expectations](https://en.wikipedia.org/wiki/Prior_probability "Prior probability"), thereby causing expectation to excessively influence sensory perception and the formation of beliefs. In approved models of [circuits](https://en.wikipedia.org/wiki/Neural_circuits "Neural circuits") that mediate [predictive coding](https://en.wikipedia.org/wiki/Predictive_coding "Predictive coding"), reduced NMDA receptor activation, could in theory result in the positive symptoms of delusions and hallucinations.[\[160\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-160)[\[161\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-161)[\[162\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-162)
From an [evolutionary](https://en.wikipedia.org/wiki/Evolutionary_psychiatry "Evolutionary psychiatry") [perspective](https://en.wikipedia.org/wiki/Evolutionary_psychology "Evolutionary psychology"), schizophrenia is regarded as an "evolutionary puzzle" because it shows high heritability (~60-80 %) and significant impairment in reproduction, yet persists at ~1 % prevalence. One hypothesis suggests that mild schizotypal traits may have historically conferred advantages (such as enhanced creativity or verbal ability,) while more severe forms represent the breakdown of these systems. Experimental models also propose that selection for language and social-cognitive complexity may have increased vulnerability to psychosis when environmental or developmental stressors intervene.[\[163\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-163)[\[164\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-164)
## Diagnosis
Main article: [Diagnosis of schizophrenia](https://en.wikipedia.org/wiki/Diagnosis_of_schizophrenia "Diagnosis of schizophrenia")
### Criteria
Schizophrenia is diagnosed based on criteria in either the *[Diagnostic and Statistical Manual of Mental Disorders](https://en.wikipedia.org/wiki/Diagnostic_and_Statistical_Manual_of_Mental_Disorders "Diagnostic and Statistical Manual of Mental Disorders")* (DSM) published by the [American Psychiatric Association](https://en.wikipedia.org/wiki/American_Psychiatric_Association "American Psychiatric Association") or the [International Statistical Classification of Diseases and Related Health Problems](https://en.wikipedia.org/wiki/ICD "ICD") (ICD) published by the [World Health Organization](https://en.wikipedia.org/wiki/World_Health_Organization "World Health Organization") (WHO). These criteria use the self-reported experiences of the person and reported abnormalities in behavior, followed by a [psychiatric assessment](https://en.wikipedia.org/wiki/Psychiatric_assessment "Psychiatric assessment"). The [mental status examination](https://en.wikipedia.org/wiki/Mental_status_examination "Mental status examination") is an important part of the assessment.[\[165\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-165) An established tool for assessing the severity of positive and negative symptoms is the [Positive and Negative Syndrome Scale](https://en.wikipedia.org/wiki/Positive_and_Negative_Syndrome_Scale "Positive and Negative Syndrome Scale") (PANSS).[\[166\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-166) This has been seen to have shortcomings relating to negative symptoms, and other scales – the *Clinical Assessment Interview for Negative Symptoms* (CAINS), and the *Brief Negative Symptoms Scale* (BNSS) have been introduced.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51) The [DSM-5](https://en.wikipedia.org/wiki/DSM-5 "DSM-5"), published in 2013, gives a *Scale to Assess the Severity of Symptom Dimensions* outlining eight dimensions of symptoms.[\[60\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Biedermann2016-60)
DSM-5 states that to be diagnosed with schizophrenia, two diagnostic criteria have to be met over the period of one month, with a significant impact on social or occupational functioning for at least six months. One of the symptoms needs to be either delusions, hallucinations, or disorganized speech. A second symptom could be one of the negative symptoms, or severely disorganized or [catatonic behaviour](https://en.wikipedia.org/wiki/Catatonia "Catatonia").[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) A different diagnosis of [schizophreniform disorder](https://en.wikipedia.org/wiki/Schizophreniform_disorder "Schizophreniform disorder") can be made before the six months needed for the diagnosis of schizophrenia.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)
In Australia, the guideline for diagnosis is for six months or more with symptoms severe enough to affect ordinary functioning.[\[167\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-167) In the UK diagnosis is based on having the symptoms for most of the time for one month, with symptoms that significantly affect the ability to work, study, or carry on ordinary daily living, and with other similar conditions ruled out.[\[168\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-168)
The ICD criteria are typically used in European countries; the DSM criteria are used predominantly in the United States and Canada, and are prevailing in research studies. In practice, agreement between the two systems is high.[\[169\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-169) The current proposal for the [ICD-11](https://en.wikipedia.org/wiki/ICD-11 "ICD-11") criteria for schizophrenia recommends adding self-disorder as a symptom.[\[42\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Heinz2016-42)
A major unresolved difference between the two diagnostic systems is that of the requirement in DSM of an impaired functional outcome. WHO for ICD argues that not all people with schizophrenia have functional deficits and so these are not specific for the diagnosis.[\[60\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Biedermann2016-60)
### Neuroimaging techniques
[Functional magnetic resonance imaging (fMRI)](https://en.wikipedia.org/wiki/Functional_MRI_methods_and_findings_in_schizophrenia "Functional MRI methods and findings in schizophrenia") has become a tool in understanding brain activity and connectivity differences in individuals with schizophrenia. Through resting-state fMRI, researchers have observed altered connectivity patterns within several key brain networks, such as the default mode network (DMN),[\[170\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-170) salience network (SN),[\[171\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-171) and central executive network (CEN).[\[172\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-172) Alterations may underlie cognitive and emotional symptoms in schizophrenia, such as disorganized thinking, impaired attention, and emotional dysregulation.
### Comorbidities
[](https://en.wikipedia.org/wiki/File:Overlapping_clinical_phenotypes_in_genes_associated_with_monogenic_forms_of_autism_spectrum_disorder_\(ASD\),_dystonia,_epilepsy_and_schizophrenia.svg)
[Euler diagram](https://en.wikipedia.org/wiki/Euler_diagram "Euler diagram") showing overlapping [clinical phenotypes](https://en.wikipedia.org/wiki/Clinical_phenotype "Clinical phenotype") in genes associated with [monogenic forms](https://en.wikipedia.org/wiki/Monogenic_disease "Monogenic disease") of [autism spectrum disorder](https://en.wikipedia.org/wiki/Autism_spectrum_disorder "Autism spectrum disorder") (ASD), [dystonia](https://en.wikipedia.org/wiki/Dystonia "Dystonia"), [epilepsy](https://en.wikipedia.org/wiki/Epilepsy "Epilepsy") and schizophrenia:
Genes associated with epilepsy
Genes associated with schizophrenia
Genes associated with autism spectrum disorder
Genes associated with dystonia
Many people with schizophrenia may have one or more [other mental disorders](https://en.wikipedia.org/wiki/Comorbidity "Comorbidity"), such as [anxiety disorders](https://en.wikipedia.org/wiki/Anxiety_disorders "Anxiety disorders"), [obsessive–compulsive disorder](https://en.wikipedia.org/wiki/Obsessive%E2%80%93compulsive_disorder "Obsessive–compulsive disorder"), or substance use disorder. These are separate disorders that require treatment.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) When comorbid with schizophrenia, substance use disorder and [antisocial personality disorder](https://en.wikipedia.org/wiki/Antisocial_personality_disorder "Antisocial personality disorder") both increase the risk for violence.[\[173\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Richard-Devantoy2009-173) Comorbid substance use disorder also increases the risk of suicide.[\[122\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Khokhar2018-122)
[Sleep disorders](https://en.wikipedia.org/wiki/Sleep_disorder "Sleep disorder") often co-occur with schizophrenia, and may be an early sign of relapse.[\[174\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Staedt2010-174) Sleep disorders are linked with positive symptoms such as [disorganized thinking](https://en.wikipedia.org/wiki/Disorganized_thinking "Disorganized thinking") and can adversely affect [cortical plasticity](https://en.wikipedia.org/wiki/Neuroplasticity "Neuroplasticity") and cognition.[\[174\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Staedt2010-174) The consolidation of memories is disrupted in sleep disorders.[\[175\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pocivavsek2018-175) They are associated with severity of illness, a poor prognosis, and poor quality of life.[\[176\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Monti2013-176)[\[177\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-177) Sleep onset and maintenance insomnia is a common symptom, regardless of whether treatment has been received or not.[\[176\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Monti2013-176) Genetic variations have been found associated with these conditions involving the [circadian rhythm](https://en.wikipedia.org/wiki/Circadian_rhythm "Circadian rhythm"), dopamine and [histamine metabolism](https://en.wikipedia.org/wiki/Histamine#Synthesis_and_metabolism "Histamine"), and signal transduction.[\[178\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-178)
Schizophrenia is also associated with a number of somatic comorbidities including [diabetes mellitus type 2](https://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 "Diabetes mellitus type 2"), [autoimmune diseases](https://en.wikipedia.org/wiki/Autoimmune_disease "Autoimmune disease"), and [cardiovascular diseases](https://en.wikipedia.org/wiki/Cardiovascular_disease "Cardiovascular disease"). The association of these with schizophrenia may be partially due to medications (e.g. [dyslipidemia](https://en.wikipedia.org/wiki/Dyslipidemia "Dyslipidemia") from antipsychotics), environmental factors (e.g. complications from an increased rate of cigarette smoking), or associated with the disorder itself (e.g. diabetes mellitus type 2 and some cardiovascular diseases are thought to be genetically linked). These somatic comorbidities contribute to reduced life expectancy among persons with the disorder.[\[179\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-179)
### Differential diagnosis
See also: [Dual diagnosis](https://en.wikipedia.org/wiki/Dual_diagnosis "Dual diagnosis")
To make a diagnosis of schizophrenia [other possible causes of psychosis need to be excluded](https://en.wikipedia.org/wiki/Diagnosis_of_exclusion "Diagnosis of exclusion").[\[180\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-180): 858 Psychotic symptoms lasting less than a month may be diagnosed as [brief psychotic disorder](https://en.wikipedia.org/wiki/Brief_psychotic_disorder "Brief psychotic disorder"), or as schizophreniform disorder. Psychosis is noted in *Other specified schizophrenia spectrum and other psychotic disorders* as a DSM-5 category. [Schizoaffective disorder](https://en.wikipedia.org/wiki/Schizoaffective_disorder "Schizoaffective disorder") is diagnosed if symptoms of [mood disorder](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder") are substantially present alongside psychotic symptoms. Psychosis that results from a general medical condition or substance is termed secondary psychosis.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)
Psychotic symptoms may be present in several other conditions, including [bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder"),[\[11\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2010-11) [borderline personality disorder](https://en.wikipedia.org/wiki/Borderline_personality_disorder "Borderline personality disorder"),[\[12\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Paris2018-12) [substance intoxication](https://en.wikipedia.org/wiki/Substance_intoxication "Substance intoxication"), [substance-induced psychosis](https://en.wikipedia.org/wiki/Substance-induced_psychosis "Substance-induced psychosis"), and a number of [drug withdrawal syndromes](https://en.wikipedia.org/wiki/Drug_withdrawal_syndrome "Drug withdrawal syndrome"). Non-bizarre delusions are also present in [delusional disorder](https://en.wikipedia.org/wiki/Delusional_disorder "Delusional disorder"), and social withdrawal in [social anxiety disorder](https://en.wikipedia.org/wiki/Social_anxiety_disorder "Social anxiety disorder"), [avoidant personality disorder](https://en.wikipedia.org/wiki/Avoidant_personality_disorder "Avoidant personality disorder") and [schizotypal personality disorder](https://en.wikipedia.org/wiki/Schizotypal_personality_disorder "Schizotypal personality disorder"). Schizotypal personality disorder has symptoms that are similar but less severe than those of schizophrenia.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) Schizophrenia occurs along with obsessive–compulsive disorder (OCD) considerably more often than could be explained by chance, although it can be difficult to distinguish obsessions that occur in OCD from the delusions of schizophrenia.[\[181\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-181) There can be considerable overlap with the symptoms of [post-traumatic stress disorder](https://en.wikipedia.org/wiki/Post-traumatic_stress_disorder "Post-traumatic stress disorder").[\[182\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-182)
A more general medical and neurological examination may be needed to rule out medical illnesses which may rarely produce psychotic schizophrenia-like symptoms, such as [metabolic disturbance](https://en.wikipedia.org/wiki/Metabolic_disorder "Metabolic disorder"), [systemic infection](https://en.wikipedia.org/wiki/Systemic_infection "Systemic infection"), [syphilis](https://en.wikipedia.org/wiki/Syphilis "Syphilis"), [HIV-associated neurocognitive disorder](https://en.wikipedia.org/wiki/HIV-associated_neurocognitive_disorder "HIV-associated neurocognitive disorder"), [epilepsy](https://en.wikipedia.org/wiki/Epilepsy "Epilepsy"), [limbic encephalitis](https://en.wikipedia.org/wiki/Limbic_encephalitis "Limbic encephalitis"), and brain lesions. Stroke, [multiple sclerosis](https://en.wikipedia.org/wiki/Multiple_sclerosis "Multiple sclerosis"), [hyperthyroidism](https://en.wikipedia.org/wiki/Hyperthyroidism "Hyperthyroidism"), [hypothyroidism](https://en.wikipedia.org/wiki/Hypothyroidism "Hypothyroidism"), and [dementias](https://en.wikipedia.org/wiki/Dementia "Dementia") such as [Alzheimer's disease](https://en.wikipedia.org/wiki/Alzheimer%27s_disease "Alzheimer's disease"), [Huntington's disease](https://en.wikipedia.org/wiki/Huntington%27s_disease "Huntington's disease"), [frontotemporal dementia](https://en.wikipedia.org/wiki/Frontotemporal_dementia "Frontotemporal dementia"), and the [Lewy body dementias](https://en.wikipedia.org/wiki/Lewy_body_dementia "Lewy body dementia") may also be associated with schizophrenia-like psychotic symptoms.[\[183\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-183) It may be necessary to rule out a [delirium](https://en.wikipedia.org/wiki/Delirium "Delirium"), which can be distinguished by visual hallucinations, acute onset and fluctuating [level of consciousness](https://en.wikipedia.org/wiki/Level_of_consciousness "Level of consciousness"), and indicates an underlying medical illness. Investigations are not generally repeated for relapse unless there is a specific *medical* indication or possible [adverse effects](https://en.wikipedia.org/wiki/Adverse_effects "Adverse effects") from [antipsychotic medication](https://en.wikipedia.org/wiki/Antipsychotic_medication "Antipsychotic medication").[\[184\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-184) In children hallucinations must be separated from typical childhood fantasies.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) It is difficult to distinguish childhood schizophrenia from autism.[\[73\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DaFonseca2018-73)
## Prevention
[Prevention](https://en.wikipedia.org/wiki/Preventive_healthcare "Preventive healthcare") of schizophrenia is difficult as there are no reliable markers for the later development of the disorder.[\[185\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-185)
[Early intervention programs](https://en.wikipedia.org/wiki/Early_intervention_in_psychosis "Early intervention in psychosis") diagnose and treat patients in the prodromal phase of the illness. There is some evidence that these programs reduce symptoms. Patients tend to prefer early treatment programs to ordinary treatment and are less likely to disengage from them. As of 2020, it is unclear whether the benefits of early treatment persist once the treatment is terminated.[\[186\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-186)
[Cognitive behavioral therapy](https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy "Cognitive behavioral therapy") may reduce the risk of psychosis in those at high risk after a year[\[187\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-187) and is recommended in this group, by the [National Institute for Health and Care Excellence](https://en.wikipedia.org/wiki/National_Institute_for_Health_and_Care_Excellence "National Institute for Health and Care Excellence") (NICE).[\[35\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NICE2014-35) Another preventive measure is to avoid drugs that have been associated with development of the disorder, including [cannabis](https://en.wikipedia.org/wiki/Cannabis_\(drug\) "Cannabis (drug)"), cocaine, and [amphetamines](https://en.wikipedia.org/wiki/Amphetamines "Amphetamines").[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)
Antipsychotics are prescribed following a first-episode psychosis, and following remission, a preventive maintenance use is continued to avoid relapse. However, it is recognized that some people do recover following a single episode and that long-term use of antipsychotics will not be needed but there is no way of identifying this group.[\[188\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Taylor2019-188)
## Management
Main article: [Management of schizophrenia](https://en.wikipedia.org/wiki/Management_of_schizophrenia "Management of schizophrenia")
The primary treatment of schizophrenia is the use of [antipsychotic medications](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic"), often in combination with [psychosocial interventions](https://en.wikipedia.org/wiki/Psychosocial_interventions "Psychosocial interventions") and [social supports](https://en.wikipedia.org/wiki/Social_support "Social support").[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28)[\[189\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-189) Community support services including drop-in centers, visits by members of a [community mental health team](https://en.wikipedia.org/wiki/Community_mental_health_service "Community mental health service"), [supported employment](https://en.wikipedia.org/wiki/Supported_employment "Supported employment"),[\[190\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-190) and support groups are common. The time between the onset of psychotic symptoms to being given treatment – the duration of untreated psychosis (DUP) – is associated with a poorer outcome in both the short term and the long term.[\[191\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-191)
[Voluntary](https://en.wikipedia.org/wiki/Voluntary_commitment "Voluntary commitment") or [involuntary](https://en.wikipedia.org/wiki/Involuntary_commitment "Involuntary commitment") admission to hospital may be imposed by doctors and courts who deem a person to be having a severe episode. In the UK, large mental hospitals termed asylums began to be closed down in the 1950s with the advent of antipsychotics, and with an awareness of the negative impact of long-term hospital stays on recovery.[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26) This process was known as [deinstitutionalization](https://en.wikipedia.org/wiki/Deinstitutionalization "Deinstitutionalization"), and community and supportive services were developed to support this change. Many other countries followed suit with the US starting in the 60s.[\[192\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-192) There still remain a smaller group of people who do not improve enough to be discharged.[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26)[\[33\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Capdevielle2009-33) In some countries that lack the necessary supportive and social services, long-term hospital stays are more usual.[\[34\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Narayan2012-34)
### Medication
[](https://en.wikipedia.org/wiki/File:Risperdal_tablets.jpg)
[Risperidone](https://en.wikipedia.org/wiki/Risperidone "Risperidone") (trade name Risperdal) is a common [atypical antipsychotic](https://en.wikipedia.org/wiki/Atypical_antipsychotic "Atypical antipsychotic") medication.
Most antipsychotics reduce overall, positive, negative, and depressive symptoms in schizophrenia, with clozapine showing the largest overall effect, though efficacy differences between drugs are mostly gradual.[\[31\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:3-31) Side-effect profiles, including weight gain, sedation, prolactin elevation, and QTc prolongation, vary more distinctly; clinicians weigh benefits against risks based on patient factors and preferences.[\[31\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:3-31)
The first-line treatment for schizophrenia is an antipsychotic. The first-generation antipsychotics, now called [typical antipsychotics](https://en.wikipedia.org/wiki/Typical_antipsychotics "Typical antipsychotics"), like [haloperidol](https://en.wikipedia.org/wiki/Haloperidol "Haloperidol"), are [dopamine antagonists](https://en.wikipedia.org/wiki/Dopamine_antagonist "Dopamine antagonist") that block D2 receptors, and affect the [neurotransmission](https://en.wikipedia.org/wiki/Neurotransmitter "Neurotransmitter") of [dopamine](https://en.wikipedia.org/wiki/Dopamine "Dopamine"). Those brought out later, the second-generation antipsychotics known as [atypical antipsychotics](https://en.wikipedia.org/wiki/Atypical_antipsychotics "Atypical antipsychotics"), including [olanzapine](https://en.wikipedia.org/wiki/Olanzapine "Olanzapine") and [risperidone](https://en.wikipedia.org/wiki/Risperidone "Risperidone"), can also have an effect on another neurotransmitter, [serotonin](https://en.wikipedia.org/wiki/Serotonin "Serotonin"). Antipsychotics can reduce the symptoms of anxiety within hours of their use, but, for other symptoms, they may take several days or weeks to reach their full effect.[\[37\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-RAISE-37)[\[193\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-nhsTreatment-193) They have little effect on negative and cognitive symptoms, which may be helped by additional psychotherapies and medications.[\[194\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-194) There is no single antipsychotic suitable for first-line treatment for everyone, as responses and tolerances vary between people.[\[195\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-195) Stopping medication may be considered after a single psychotic episode where there has been a full recovery with no symptoms for twelve months. Repeated relapses worsen the long-term outlook and the risk of relapse following a second episode is high, and long-term treatment is usually recommended.[\[196\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-196)[\[197\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Harrow2013-197)
About half of those with schizophrenia will respond favourably to antipsychotics, and have a good return of functioning.[\[198\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-198) However, positive symptoms persist in up to a third of people. Following two trials of different antipsychotics over six weeks, that also prove ineffective, they will be classed as having treatment-resistant schizophrenia (TRS), and [clozapine](https://en.wikipedia.org/wiki/Clozapine "Clozapine") will be offered.[\[199\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-199)[\[30\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Siskind2017-30) Clozapine is of benefit to around half of this group although it has the potentially serious side effect of [agranulocytosis](https://en.wikipedia.org/wiki/Agranulocytosis "Agranulocytosis") (lowered [white blood cell](https://en.wikipedia.org/wiki/White_blood_cell "White blood cell") count) in less than 4% of people.[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28)[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)[\[200\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-200)
About 30 to 50 percent of people with schizophrenia do not accept that they have an illness or comply with their recommended treatment.[\[201\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-201) For those who are unwilling or unable to take medication regularly, [long-acting injections](https://en.wikipedia.org/wiki/Injection_\(medicine\)#Depot "Injection (medicine)") of antipsychotics may be used,[\[202\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-202) which reduce the risk of relapse to a greater degree than oral medications.[\[203\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-203) When used in combination with psychosocial interventions, they may improve long-term [adherence](https://en.wikipedia.org/wiki/Adherence_\(medicine\) "Adherence (medicine)") to treatment.[\[204\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Depo06-204)
A 2025 meta-analysis showed xanomeline and trospium's effect in the improvement of symptoms of schizophrenia.[\[205\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-205) The [fixed-dose combination](https://en.wikipedia.org/wiki/Fixed-dose_combination "Fixed-dose combination") medication [xanomeline/trospium chloride](https://en.wikipedia.org/wiki/Xanomeline/trospium_chloride "Xanomeline/trospium chloride") (Cobenfy) was approved for medical use in the United States in September 2024.[\[206\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-FDA_PR_20240926-206)[\[207\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-207) It is the first [cholinergic agonist](https://en.wikipedia.org/wiki/Cholinergic_agonist "Cholinergic agonist") approved by the US [Food and Drug Administration](https://en.wikipedia.org/wiki/Food_and_Drug_Administration "Food and Drug Administration") (FDA) to treat schizophrenia.[\[206\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-FDA_PR_20240926-206)
Negative and cognitive symptoms are an unmet clinical need in antipsychotic-based treatment approaches. Psychostimulant drugs have been found effective in the treatment of negative symptoms, but are rarely prescribed due to concerns about the excacerbation of positive symptoms.[\[54\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lindenmayer_Nasrallah_Pucci_systematic_review-54) It is possible that low-dose psychedelic therapies could be of benefit in schizophrenia through their prosocial and procognitive effects, although there is a serious risk that high dose psychedelic therapies could lead to worsening of positive symptoms.[\[208\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-208)
#### Adverse effects
Further information: [Antipsychotic § Adverse effects](https://en.wikipedia.org/wiki/Antipsychotic#Adverse_effects "Antipsychotic")
[Extrapyramidal symptoms](https://en.wikipedia.org/wiki/Extrapyramidal_symptoms "Extrapyramidal symptoms"), including [akathisia](https://en.wikipedia.org/wiki/Akathisia#Drug-induced "Akathisia"), are associated with all commercially available [antipsychotic](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic") to varying degrees.[\[209\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Chow2020-209): 566 There is little evidence that second generation antipsychotics have reduced levels of extrapyramidical symptoms compared to typical antipsychotics.[\[209\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Chow2020-209): 566 [Tardive dyskinesia](https://en.wikipedia.org/wiki/Tardive_dyskinesia "Tardive dyskinesia") can occur due to long-term use of antipsychotics, developing after months or years of use.[\[210\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-210) The antipsychotic [clozapine](https://en.wikipedia.org/wiki/Clozapine "Clozapine") is also associated with [thromboembolism](https://en.wikipedia.org/wiki/Thromboembolism "Thromboembolism") (including [pulmonary embolism](https://en.wikipedia.org/wiki/Pulmonary_embolism "Pulmonary embolism")), [myocarditis](https://en.wikipedia.org/wiki/Myocarditis "Myocarditis"), and [cardiomyopathy](https://en.wikipedia.org/wiki/Cardiomyopathy "Cardiomyopathy").
### Psychosocial interventions
Further information: [Management of schizophrenia § Psychosocial](https://en.wikipedia.org/wiki/Management_of_schizophrenia#Psychosocial "Management of schizophrenia")
A number of psychosocial interventions that include several types of [psychotherapy](https://en.wikipedia.org/wiki/Psychotherapy "Psychotherapy") may be useful in the treatment of schizophrenia such as: [family therapy](https://en.wikipedia.org/wiki/Family_therapy "Family therapy"),[\[211\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pharoah2010-211) [group therapy](https://en.wikipedia.org/wiki/Group_therapy "Group therapy"), cognitive remediation therapy (CRT),[\[212\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-212) cognitive behavioral therapy (CBT),[\[213\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-213) and [metacognitive training](https://en.wikipedia.org/wiki/Metacognitive_training "Metacognitive training").[\[214\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-214)[\[215\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-215) Skills training, help with substance use, and weight management – often needed as a side effect of an antipsychotic – are also offered.[\[216\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-216) In the US, interventions for first episode psychosis have been brought together in an overall approach known as [coordinated speciality care](https://en.wikipedia.org/wiki/Coordinated_speciality_care "Coordinated speciality care") (CSC) and also includes support for education.[\[37\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-RAISE-37) In the UK *care across all phases* is a similar approach that covers many of the treatment guidelines recommended.[\[35\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NICE2014-35) The aim is to reduce the number of relapses and stays in the hospital.[\[211\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pharoah2010-211)
Other support services for education, employment, and housing are usually offered. For people with severe schizophrenia, who are discharged from a stay in the hospital, these services are often brought together in an integrated approach to offer support in the community away from the hospital setting. In addition to medicine management, housing, and finances, assistance is given for more routine matters such as help with shopping and using public transport. This approach is known as [assertive community treatment](https://en.wikipedia.org/wiki/Assertive_community_treatment "Assertive community treatment") (ACT) and has been shown to achieve positive results in symptoms, social functioning and quality of life.[\[217\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-217)[\[218\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-218) Another more intense approach is known as *intensive care management* (ICM). ICM is a stage further than ACT and emphasises support of high intensity in smaller caseloads, (less than twenty). This approach is to provide long-term care in the community. Studies show that ICM improves many of the relevant outcomes including social functioning.[\[219\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-219)
Some studies have shown little evidence for the effectiveness of CBT in either reducing symptoms or preventing relapse.[\[220\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-220)[\[221\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jones2018-221) However, other studies have found that CBT does improve overall psychotic symptoms (when in use with medication) and it has been recommended in Canada, but has been seen to have no effect on social function, relapse, or quality of life.[\[222\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-222) In the UK it is recommended as an add-on therapy in the treatment of schizophrenia.[\[193\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-nhsTreatment-193)[\[221\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jones2018-221) [Arts therapies](https://en.wikipedia.org/wiki/Expressive_therapies "Expressive therapies") are seen to improve negative symptoms in some people, and are recommended by NICE in the UK.[\[193\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-nhsTreatment-193) This approach is criticised as having not been well-researched,[\[223\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-223)[\[224\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-224) and arts therapies are not recommended in Australian guidelines for example.[\[225\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-225) [Peer support](https://en.wikipedia.org/wiki/Peer_support#In_mental_health "Peer support"), in which people with [personal experience](https://en.wikipedia.org/wiki/Experiential_knowledge "Experiential knowledge") of schizophrenia, provide help to each other, is of unclear benefit.[\[226\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-226)
### Other
Exercise including aerobic exercise has been shown to improve positive and negative symptoms, cognition, working memory, and improve quality of life.[\[227\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Girdler2019-227)[\[228\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2017-228) Exercise has also been shown to increase the volume of the [hippocampus](https://en.wikipedia.org/wiki/Hippocampus "Hippocampus") in those with schizophrenia. A decrease in hippocampal volume is one of the factors linked to the development of the disease.[\[227\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Girdler2019-227) However, there still remains the problem of increasing motivation for, and maintaining participation in physical activity.[\[229\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-229) Supervised sessions are recommended.[\[228\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2017-228) In the UK healthy eating advice is offered alongside exercise programs.[\[230\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-230)
An inadequate diet is often found in schizophrenia, and associated vitamin deficiencies including those of [folate](https://en.wikipedia.org/wiki/Folate "Folate"), and [vitamin D](https://en.wikipedia.org/wiki/Vitamin_D_deficiency#In_schizophrenia "Vitamin D deficiency") are linked to the risk factors for the development of schizophrenia and for early death including heart disease.[\[231\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2018-231)[\[232\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rastogi2020-232) Those with schizophrenia possibly have the worst diet of all the mental disorders. Lower levels of folate and vitamin D have been noted as significantly lower in first episode psychosis.[\[231\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2018-231) The use of supplemental folate is recommended.[\[233\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-233) A [zinc deficiency](https://en.wikipedia.org/wiki/Zinc_deficiency "Zinc deficiency") has also been noted.[\[234\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2019-234) [Vitamin B12](https://en.wikipedia.org/wiki/Vitamin_B12 "Vitamin B12") is also often deficient and this is linked to worse symptoms. Supplementation with B vitamins has been shown to significantly improve symptoms, and to put in reverse some of the cognitive deficits.[\[231\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2018-231) It is also suggested that the noted dysfunction in gut microbiota might benefit from the use of [probiotics](https://en.wikipedia.org/wiki/Probiotics "Probiotics").[\[234\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2019-234)
## Prognosis
Main article: [Prognosis of schizophrenia](https://en.wikipedia.org/wiki/Prognosis_of_schizophrenia "Prognosis of schizophrenia")
See also: [Physical health in schizophrenia](https://en.wikipedia.org/wiki/Physical_health_in_schizophrenia "Physical health in schizophrenia")
[](https://en.wikipedia.org/wiki/File:Schizophrenia_world_map_-_DALY_-_WHO2004.svg)
[Disability-adjusted life years](https://en.wikipedia.org/wiki/Disability-adjusted_life_year "Disability-adjusted life year") lost due to schizophrenia per 100,000 inhabitants in 2004
| | |
|---|---|
| no data ≤ 185 185–197 197–207 207–218 218–229 229–240 | 240–251 251–262 262–273 273–284 284–295 ≥ 295 |
Schizophrenia has great human and economic costs.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) It decreases life expectancy by between 10[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13) and 28 years.[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) This is primarily because of its association with heart disease,[\[235\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kritharides2017-235) diabetes,[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) [obesity](https://en.wikipedia.org/wiki/Obesity "Obesity"), poor diet, a [sedentary lifestyle](https://en.wikipedia.org/wiki/Sedentary_lifestyle "Sedentary lifestyle"), and smoking, with an increased rate of suicide playing a lesser role.[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13)[\[236\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-236) Side effects of antipsychotics may also increase the risk.[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13)
Almost 40% of those with schizophrenia die from complications of cardiovascular disease which is seen to be increasingly associated.[\[232\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rastogi2020-232) An underlying factor of sudden cardiac death may be [Brugada syndrome](https://en.wikipedia.org/wiki/Brugada_syndrome "Brugada syndrome") (BrS) – BrS mutations that overlap with those linked with schizophrenia are the [calcium channel](https://en.wikipedia.org/wiki/Calcium_channel "Calcium channel") mutations.[\[232\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rastogi2020-232) BrS may also be drug-induced from certain antipsychotics and antidepressants.[\[232\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rastogi2020-232) [Primary polydipsia](https://en.wikipedia.org/wiki/Primary_polydipsia "Primary polydipsia"), or excessive fluid intake, is relatively common in people with chronic schizophrenia.[\[237\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-237)[\[238\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rizvi2019-238) This may lead to [hyponatremia](https://en.wikipedia.org/wiki/Hyponatremia "Hyponatremia") which can be life-threatening. Antipsychotics can lead to a [dry mouth](https://en.wikipedia.org/wiki/Xerostomia#Drug_induced_xerostomia "Xerostomia"), but there are several other factors that may contribute to the disorder; it may reduce life expectancy by 13 percent.[\[238\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rizvi2019-238) Barriers to improving the mortality rate in schizophrenia are poverty, overlooking the symptoms of other illnesses, stress, stigma, and medication side effects.[\[239\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-239)[\[240\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:0-240)[\[241\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:1-241)
Schizophrenia is a major cause of [disability](https://en.wikipedia.org/wiki/Disability "Disability"). In 2016, it was classed as the 12th most disabling condition.[\[242\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-242) Approximately 75% of people with schizophrenia have ongoing disability with relapses.[\[243\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-243) Some people do recover completely and others function well in society.[\[244\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-244) Most people with schizophrenia live independently with community support.[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28) About 85% are unemployed.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) In people with a first episode of psychosis in schizophrenia a good long-term outcome occurs in 31%, an intermediate outcome in 42% and a poor outcome in 31%.[\[245\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-245) Males are affected more often than females, and have a worse outcome.[\[246\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-246) Studies showing that outcomes for schizophrenia appear better in the [developing](https://en.wikipedia.org/wiki/Developing_world "Developing world") than the [developed world](https://en.wikipedia.org/wiki/Developed_world "Developed world")[\[247\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Isa07-247) have been questioned.[\[248\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-248) Social problems, such as long-term unemployment, poverty, homelessness, exploitation, [stigmatization](https://en.wikipedia.org/wiki/Mental_disorder#Stigma "Mental disorder") and victimization are common consequences, and lead to [social exclusion](https://en.wikipedia.org/wiki/Social_exclusion "Social exclusion").[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26)[\[27\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Charleson2018-27)[\[240\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:0-240)[\[241\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:1-241)
There is a higher than average [suicide rate](https://en.wikipedia.org/wiki/Suicide_rate "Suicide rate") associated with schizophrenia estimated at 5% to 6%, most often occurring in the period following onset or first hospital admission.[\[19\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2019-19)[\[29\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jop2010-29) Several times more (20 to 40%) attempt suicide at least once.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[100\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Chiang2016-100) There are a variety of risk factors, including male sex, depression, a high [IQ](https://en.wikipedia.org/wiki/IQ "IQ"),[\[249\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-249) heavy smoking,[\[250\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-250) and substance use.[\[122\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Khokhar2018-122) Repeated relapse is linked to an increased risk of suicidal behavior.[\[188\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Taylor2019-188) The use of clozapine can reduce the risk of suicide, and of aggression.[\[251\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-251)
A strong association between [schizophrenia and tobacco smoking](https://en.wikipedia.org/wiki/Schizophrenia_and_tobacco_smoking "Schizophrenia and tobacco smoking") has been shown in worldwide studies.[\[252\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-252)[\[253\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Keltner2006-253) [Smoking](https://en.wikipedia.org/wiki/Tobacco_smoking "Tobacco smoking") is especially high in those diagnosed with schizophrenia, with estimates ranging from 80 to 90% being regular smokers, as compared to 20% of the general population.[\[253\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Keltner2006-253) Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content.[\[41\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSMIV-41) Some propose that this is in an effort to improve symptoms.[\[254\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-254) Among people with schizophrenia use of cannabis is also common.[\[122\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Khokhar2018-122)
Schizophrenia leads to an increased risk of dementia.[\[255\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-255)
### Violence
Most people with schizophrenia are not aggressive, and are more likely to be victims of violence rather than perpetrators.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) People with schizophrenia are commonly exploited and victimized by violent crime as part of a broader dynamic of social exclusion.[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26)[\[27\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Charleson2018-27) People diagnosed with schizophrenia are also subject to forced drug injections, seclusion, and restraint at high rates.[\[32\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BeckerKilian2006-32)[\[33\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Capdevielle2009-33)
The risk of violence by people with schizophrenia is small. There are minor subgroups where the risk is high.[\[173\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Richard-Devantoy2009-173) This risk is usually associated with a comorbid disorder such as a substance use disorder – in particular alcohol, or with antisocial personality disorder.[\[173\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Richard-Devantoy2009-173) Substance use disorder is strongly linked, and other risk factors are linked to deficits in cognition and social cognition including facial perception and insight that are in part included in [theory of mind](https://en.wikipedia.org/wiki/Theory_of_mind "Theory of mind") impairments.[\[256\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-256)[\[257\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-257) Poor cognitive functioning, decision-making, and facial perception may contribute to making a wrong judgement of a situation that could result in an inappropriate response such as violence.[\[258\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-258) These associated risk factors are also present in antisocial personality disorder which when present as a comorbid disorder greatly increases the risk of violence.[\[259\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-259)[\[260\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-260)
## Epidemiology
Main article: [Epidemiology of schizophrenia](https://en.wikipedia.org/wiki/Epidemiology_of_schizophrenia "Epidemiology of schizophrenia")
[](https://en.wikipedia.org/wiki/File:Schizophrenia_world_map-Deaths_per_million_persons-WHO2012.svg)
Deaths per million persons due to schizophrenia in 2012
0–0
1–1
2–2
3–3
4–6
7–20
In 2017,\[*[needs update](https://en.wikipedia.org/wiki/Wikipedia:Manual_of_Style/Dates_and_numbers#Chronological_items "Wikipedia:Manual of Style/Dates and numbers")*\] the [Global Burden of Disease Study](https://en.wikipedia.org/wiki/Global_Burden_of_Disease_Study "Global Burden of Disease Study") estimated there were 1.1 million new cases;[\[21\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2018-21) in 2022 the World Health Organization (WHO) reported a total of 24 million cases globally.[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2) Schizophrenia affects around 0.3–0.7% of people at some point in their life.[\[20\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Javitt2014-20)[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) In areas of conflict this figure can rise to between 4.0 and 6.5%.[\[261\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-261) It occurs 1.4 times more frequently in males than females and typically appears earlier in men.[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)
Worldwide, schizophrenia is the most common [psychotic disorder](https://en.wikipedia.org/wiki/Psychotic_disorder "Psychotic disorder").[\[57\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kar2016-57) The frequency of schizophrenia varies across the world,[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) within countries,[\[262\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-262) and at the local and neighborhood level;[\[263\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-263) this variation in [prevalence](https://en.wikipedia.org/wiki/Prevalence "Prevalence") between studies over time, across geographical locations, and by gender is as high as fivefold.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)
Schizophrenia causes approximately one percent of worldwide [disability adjusted life years](https://en.wikipedia.org/wiki/Disability_adjusted_life_years "Disability adjusted life years")\[*[needs update](https://en.wikipedia.org/wiki/Wikipedia:Manual_of_Style/Dates_and_numbers#Chronological_items "Wikipedia:Manual of Style/Dates and numbers")*\][\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86) and resulted in 17,000 deaths in 2015.[\[16\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2015-16)
In 2000,\[*[needs update](https://en.wikipedia.org/wiki/Wikipedia:Manual_of_Style/Dates_and_numbers#Chronological_items "Wikipedia:Manual of Style/Dates and numbers")*\] WHO found the percentage of people affected and the number of new cases that develop each year is roughly similar around the world, with age-standardized prevalence per 100,000 ranging from 343 in Africa to 544 in Japan and Oceania for men, and from 378 in Africa to 527 in Southeastern Europe for women.[\[264\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-264)
## History
Main article: [History of schizophrenia](https://en.wikipedia.org/wiki/History_of_schizophrenia "History of schizophrenia")
### Conceptual development
Main article: [History of schizophrenia § Conceptual development](https://en.wikipedia.org/wiki/History_of_schizophrenia#Conceptual_development "History of schizophrenia")
Further information: [Dementia praecox](https://en.wikipedia.org/wiki/Dementia_praecox "Dementia praecox")
[](https://en.wikipedia.org/wiki/File:Eugen_bleuler.jpg)
The term "schizophrenia" was coined by [Eugen Bleuler](https://en.wikipedia.org/wiki/Eugen_Bleuler "Eugen Bleuler").
Accounts of a schizophrenia-like [syndrome](https://en.wikipedia.org/wiki/Syndrome "Syndrome") are rare in records before the 19th century; the earliest case reports were in 1797 and 1809.[\[265\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-265) The term *[dementia praecox](https://en.wikipedia.org/wiki/Dementia_praecox "Dementia praecox")* ("premature dementia") was used by German psychiatrist Heinrich Schüle in 1886 and then in 1891 by [Arnold Pick](https://en.wikipedia.org/wiki/Arnold_Pick "Arnold Pick") in a case report of [hebephrenia](https://en.wikipedia.org/wiki/Hebephrenia "Hebephrenia"). In 1893 [Emil Kraepelin](https://en.wikipedia.org/wiki/Emil_Kraepelin "Emil Kraepelin") used the term in making a distinction, known as the [Kraepelinian dichotomy](https://en.wikipedia.org/wiki/Kraepelinian_dichotomy "Kraepelinian dichotomy"), between the two psychoses: dementia praecox and [manic depression](https://en.wikipedia.org/wiki/Manic_depression "Manic depression") (now called [bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder")).[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13) When it became evident that the disorder was not a degenerative dementia, it was renamed *schizophrenia* by [Eugen Bleuler](https://en.wikipedia.org/wiki/Eugen_Bleuler "Eugen Bleuler") in 1908.[\[266\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kuhn2004-266)
The word *schizophrenia* ("splitting of the mind") is [Modern Latin](https://en.wikipedia.org/wiki/Neo-Latin "Neo-Latin"), derived from the [Greek](https://en.wikipedia.org/wiki/Ancient_Greek "Ancient Greek") *schizein* ([Ancient Greek](https://en.wikipedia.org/wiki/Ancient_Greek_language "Ancient Greek language"): σχίζειν, [lit.](https://en.wikipedia.org/wiki/Literal_translation "Literal translation")'to split') and *phrēn* ([Ancient Greek](https://en.wikipedia.org/wiki/Ancient_Greek_language "Ancient Greek language"): φρήν, [lit.](https://en.wikipedia.org/wiki/Literal_translation "Literal translation")'mind').[\[267\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-267) Its use was intended to describe the separation of function between [personality](https://en.wikipedia.org/wiki/Personality_psychology "Personality psychology"), [thinking](https://en.wikipedia.org/wiki/Thought "Thought"), memory, and perception.[\[266\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kuhn2004-266)
In the early 20th century, the psychiatrist [Kurt Schneider](https://en.wikipedia.org/wiki/Kurt_Schneider "Kurt Schneider") categorized the psychotic symptoms of schizophrenia into two groups: hallucinations and delusions. The hallucinations were listed as specific to auditory and the delusions included thought disorders. These were seen as important symptoms, termed [*first-rank*](https://en.wikipedia.org/wiki/Kurt_Schneider#First-rank_symptoms "Kurt Schneider"). The most common first-rank symptom was found to belong to thought disorders.\[*[page needed](https://en.wikipedia.org/wiki/Wikipedia:Citing_sources "Wikipedia:Citing sources")*\][\[268\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-268)\[*[page needed](https://en.wikipedia.org/wiki/Wikipedia:Citing_sources "Wikipedia:Citing sources")*\][\[269\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-269) In 2013 the first-rank symptoms were excluded from the DSM-5 criteria;[\[270\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-270) while they may not be useful in diagnosing schizophrenia, they can assist in [differential diagnosis](https://en.wikipedia.org/wiki/Differential_diagnosis "Differential diagnosis").[\[271\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-271)
Subtypes of schizophrenia—classified as paranoid, disorganized, [catatonic](https://en.wikipedia.org/wiki/Catatonia "Catatonia"), undifferentiated, and residual—were difficult to distinguish and are no longer recognized as separate conditions by DSM-5 (2013) or ICD-11.[\[272\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Reed2019-272)[\[273\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-273)[\[274\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-274)
### Breadth of diagnosis
Before the 1960s, nonviolent [petty criminals](https://en.wikipedia.org/wiki/Petty_criminal "Petty criminal") and women were sometimes diagnosed with schizophrenia, categorizing the latter as ill for not performing their duties as wives and mothers.[\[275\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lane2010-275) In the mid- to late 1960s, black men were categorized as "hostile and aggressive" and diagnosed as schizophrenic at much higher rates, their [civil rights](https://en.wikipedia.org/wiki/Civil_rights_movement "Civil rights movement") and [Black Power](https://en.wikipedia.org/wiki/Black_Power "Black Power") activism labeled as delusions.[\[275\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lane2010-275)[\[276\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-276)
In the early 1970s in the United States, the diagnostic model for schizophrenia was broad and clinically based using [DSM II](https://en.wikipedia.org/wiki/DSM_II "DSM II"). Schizophrenia was diagnosed far more in the United States than in Europe, where the [ICD-9](https://en.wikipedia.org/wiki/ICD-9 "ICD-9") criteria were followed. The US model was criticised for failing to demarcate clearly those people with a mental illness. In 1980 DSM III was published and showed a shift in focus from the clinically based [biopsychosocial model](https://en.wikipedia.org/wiki/Biopsychosocial_model "Biopsychosocial model") to a reason-based medical model.\[*[clarification needed](https://en.wikipedia.org/wiki/Wikipedia:Please_clarify "Wikipedia:Please clarify")*\][\[277\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-277) DSM IV brought an increased focus on an evidence-based medical model.[\[278\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-278)
### Historical treatment
Main article: [History of schizophrenia § Development of treatments in the 20th century](https://en.wikipedia.org/wiki/History_of_schizophrenia#Development_of_treatments_in_the_20th_century "History of schizophrenia")
[](https://en.wikipedia.org/wiki/File:Chlorpromazine-3D-vdW.png)
A molecule of [chlorpromazine](https://en.wikipedia.org/wiki/Chlorpromazine "Chlorpromazine"), the first antipsychotic developed in the 1950s
In the 1930s a number of shock procedures which induced seizures (convulsions) or comas were used to treat schizophrenia.[\[279\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jones2000-279) [Insulin shock](https://en.wikipedia.org/wiki/Insulin_shock_therapy "Insulin shock therapy") involved injecting large doses of [insulin](https://en.wikipedia.org/wiki/Insulin "Insulin") to induce comas, which in turn produced [hypoglycemia](https://en.wikipedia.org/wiki/Hypoglycemia "Hypoglycemia") and convulsions.[\[279\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jones2000-279)[\[280\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-280) The use of electricity to induce seizures was in use as [electroconvulsive therapy](https://en.wikipedia.org/wiki/Electroconvulsive_therapy "Electroconvulsive therapy") (ECT) by 1938.[\[281\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-281)
Carried out from the 1930s until the 1970s in the United States and until the 1980s in France, [psychosurgery](https://en.wikipedia.org/wiki/Psychosurgery "Psychosurgery"), including such modalities as the [lobotomy](https://en.wikipedia.org/wiki/Lobotomy "Lobotomy"), is recognized as a [human rights abuse](https://en.wikipedia.org/wiki/Human_rights_abuse "Human rights abuse").[\[282\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-282)[\[283\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-283) In the mid-1950s, [chlorpromazine](https://en.wikipedia.org/wiki/Chlorpromazine "Chlorpromazine"), the first [typical antipsychotic](https://en.wikipedia.org/wiki/Typical_antipsychotic "Typical antipsychotic"), was introduced,[\[284\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-284) followed in the 1970s by clozapine, the first [atypical antipsychotic](https://en.wikipedia.org/wiki/Atypical_antipsychotic "Atypical antipsychotic").[\[285\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-285)
### Political abuse
Further information: [Political abuse of psychiatry](https://en.wikipedia.org/wiki/Political_abuse_of_psychiatry "Political abuse of psychiatry")
From the 1960s until 1989, psychiatrists in the [USSR](https://en.wikipedia.org/wiki/Soviet_Union "Soviet Union") and [Eastern Bloc](https://en.wikipedia.org/wiki/Eastern_Bloc "Eastern Bloc") diagnosed thousands of people with [sluggish schizophrenia](https://en.wikipedia.org/wiki/Sluggish_schizophrenia "Sluggish schizophrenia"),[\[286\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-286)[\[287\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-287) without signs of psychosis, based on "the assumption that symptoms would later appear".[\[288\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-288) Now discredited, the diagnosis provided a convenient way to confine political dissidents.[\[289\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Merskey1988-289)
## Society and culture
See also: [List of people with schizophrenia](https://en.wikipedia.org/wiki/List_of_people_with_schizophrenia "List of people with schizophrenia") and [Religion and schizophrenia](https://en.wikipedia.org/wiki/Religion_and_schizophrenia "Religion and schizophrenia")
In the United States, the annual cost of schizophrenia – including direct costs (outpatient, inpatient, drugs, and long-term care) and non-healthcare costs (law enforcement, reduced workplace productivity, and unemployment) – was estimated at \$62.7 billion for the year 2002.[\[290\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-290)[\[a\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-293) In the UK the cost in 2016 was put at £11.8 billion per year with a third of that figure directly attributable to the cost of hospital, social care and treatment.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)
### Stigma
[](https://en.wikipedia.org/wiki/File:John_Forbes_Nash,_Jr._by_Peter_Badge.jpg)
[John Nash](https://en.wikipedia.org/wiki/John_Forbes_Nash "John Forbes Nash"), an American mathematician and joint recipient of the 1994 [Nobel Memorial Prize in Economic Sciences](https://en.wikipedia.org/wiki/Nobel_Memorial_Prize_in_Economic_Sciences "Nobel Memorial Prize in Economic Sciences"), had schizophrenia. His life was the subject of the 1998 book, *[A Beautiful Mind](https://en.wikipedia.org/wiki/A_Beautiful_Mind_\(book\) "A Beautiful Mind (book)")*, by [Sylvia Nasar](https://en.wikipedia.org/wiki/Sylvia_Nasar "Sylvia Nasar").
In 2002, the term for schizophrenia in Japan was changed from *seishin-bunretsu-byō* (精神分裂病; lit. 'mind-split disease') to *tōgō-shitchō-shō* (統合失調症; lit. 'integration–dysregulation syndrome') to reduce [stigma](https://en.wikipedia.org/wiki/Social_stigma "Social stigma") and confusion with "multiple personalities".[\[293\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-294) The new name, also interpreted as "integration disorder", was inspired by the biopsychosocial model.[\[294\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-295) A similar change was made in South Korea in 2012 to attunement disorder.[\[295\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-296)
Stigma may prevent further research and treatment as in history treated some in the past invariably worse to recovery.[\[240\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:0-240)[\[241\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:1-241)
### Cultural depictions
Media coverage, especially movies, reinforce the public perception of an association between schizophrenia and violence.[\[296\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-297)[\[241\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:1-241)[\[240\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:0-240) A majority of movies have historically depicted characters with schizophrenia as criminal, dangerous, violent, unpredictable and homicidal, and depicted delusions and hallucinations as the main symptoms of schizophrenic characters, ignoring other common symptoms,[\[297\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Owen2012-298) furthering stereotypes of schizophrenia including the idea of a split personality.[\[298\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-299)
The book *[A Beautiful Mind](https://en.wikipedia.org/wiki/A_Beautiful_Mind_\(book\) "A Beautiful Mind (book)")* chronicled the life of [John Forbes Nash](https://en.wikipedia.org/wiki/John_Forbes_Nash "John Forbes Nash") who had been diagnosed with schizophrenia and won the [Nobel Memorial Prize in Economic Sciences](https://en.wikipedia.org/wiki/Nobel_Memorial_Prize_in_Economic_Sciences "Nobel Memorial Prize in Economic Sciences"). The book was made into a [film with the same name](https://en.wikipedia.org/wiki/A_Beautiful_Mind_\(film\) "A Beautiful Mind (film)"); an earlier documentary film was *[A Brilliant Madness](https://en.wikipedia.org/wiki/A_Brilliant_Madness "A Brilliant Madness")*.
In the UK, guidelines for reporting conditions and award campaigns have shown a reduction in negative reporting since 2013.[\[299\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-300)
In 1964 a [case study](https://en.wikipedia.org/wiki/Case_study "Case study") of three males diagnosed with schizophrenia who each had the delusional belief that they were [Jesus Christ](https://en.wikipedia.org/wiki/Jesus "Jesus") was published as *[The Three Christs of Ypsilanti](https://en.wikipedia.org/wiki/The_Three_Christs_of_Ypsilanti "The Three Christs of Ypsilanti")*; a film with the title *[Three Christs](https://en.wikipedia.org/wiki/Three_Christs "Three Christs")* was released in 2020.[\[300\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-301)[\[301\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-302)
## Research
See also: [Animal models of schizophrenia](https://en.wikipedia.org/wiki/Animal_models_of_schizophrenia "Animal models of schizophrenia") and [List of investigational antipsychotics](https://en.wikipedia.org/wiki/List_of_investigational_antipsychotics "List of investigational antipsychotics")
A 2015 Cochrane review found unclear evidence of benefit from brain stimulation techniques to treat the positive symptoms of schizophrenia, in particular auditory verbal hallucinations (AVHs).[\[302\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-303) Most studies focus on [transcranial direct-current stimulation](https://en.wikipedia.org/wiki/Transcranial_direct-current_stimulation "Transcranial direct-current stimulation") (tDCM), and [repetitive transcranial magnetic stimulation](https://en.wikipedia.org/wiki/Repetitive_transcranial_magnetic_stimulation "Repetitive transcranial magnetic stimulation") (rTMS).[\[303\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Nathou2019-304) Techniques based on focused ultrasound for [deep brain stimulation](https://en.wikipedia.org/wiki/Deep_brain_stimulation "Deep brain stimulation") could provide insight for the treatment of AVHs.[\[303\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Nathou2019-304)
The study of potential [biomarkers](https://en.wikipedia.org/wiki/Biomarker_\(medicine\) "Biomarker (medicine)") that would help in diagnosis and treatment of schizophrenia is an active area of research as of 2020. Possible biomarkers include markers of inflammation,[\[99\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Upthegrove2020-99) [neuroimaging](https://en.wikipedia.org/wiki/Functional_MRI_methods_and_findings_in_schizophrenia "Functional MRI methods and findings in schizophrenia"),[\[304\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-305) [brain-derived neurotrophic factor](https://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor "Brain-derived neurotrophic factor") (BDNF),[\[305\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-306) and speech analysis. Some markers such as [C-reactive protein](https://en.wikipedia.org/wiki/C-reactive_protein "C-reactive protein") are useful in detecting levels of inflammation implicated in some psychiatric disorders but they are not disorder-specific. Other inflammatory cytokines are found to be elevated in first episode psychosis and acute relapse that are normalized after treatment with antipsychotics, and these may be considered as state markers.[\[306\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-307) Deficits in [sleep spindles](https://en.wikipedia.org/wiki/Sleep_spindle "Sleep spindle") in schizophrenia may serve as a marker of an impaired thalamocortical circuit, and a mechanism for memory impairment.[\[175\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pocivavsek2018-175) [MicroRNAs](https://en.wikipedia.org/wiki/MicroRNA "MicroRNA") are highly influential in early neuronal development, and their disruption is implicated in several [CNS](https://en.wikipedia.org/wiki/Central_nervous_system "Central nervous system") disorders; [circulating microRNAs](https://en.wikipedia.org/wiki/Circulating_microRNA "Circulating microRNA") (cimiRNAs) are found in [body fluids](https://en.wikipedia.org/wiki/Body_fluid "Body fluid") such as blood and cerebrospinal fluid, and changes in their levels are seen to relate to changes in microRNA levels in specific regions of brain tissue. These studies suggest that cimiRNAs have the potential to be early and accurate biomarkers in a number of disorders including schizophrenia.[\[307\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-308)[\[308\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-309)
[Ongoing fMRI research](https://en.wikipedia.org/wiki/Functional_MRI_methods_and_findings_in_schizophrenia "Functional MRI methods and findings in schizophrenia") aims to identify biomarkers within these brain networks,[\[309\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-310) potentially aiding in earlier diagnosis and better tracking of treatment responses in schizophrenia.
## Explanatory notes
1. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-293)** A 2007 review stated that the 2002 estimate was still the best available,[\[291\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-291) and a 2018 review cited the same \$62.7 billion.[\[292\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-292)
## References
1. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-1)**
[Jones D](https://en.wikipedia.org/wiki/Daniel_Jones_\(phonetician\) "Daniel Jones (phonetician)") (2003) \[1917\]. Roach P, Hartmann J, Setter J (eds.). *English Pronouncing Dictionary*. Cambridge University Press. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)")
[978-3-12-539683-8](https://en.wikipedia.org/wiki/Special:BookSources/978-3-12-539683-8 "Special:BookSources/978-3-12-539683-8")
.
2. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-WHO2022_2-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-WHO2022_2-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-WHO2022_2-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-WHO2022_2-3) [***e***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-WHO2022_2-4)
["Schizophrenia Fact sheet"](https://www.who.int/news-room/fact-sheets/detail/schizophrenia). [World Health Organization](https://en.wikipedia.org/wiki/World_Health_Organization "World Health Organization"). 10 January 2022. Retrieved 23 August 2022.
3. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIH2022_3-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIH2022_3-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIH2022_3-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIH2022_3-3) [***e***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIH2022_3-4) [***f***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIH2022_3-5) [***g***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIH2022_3-6)
["Schizophrenia"](https://www.nimh.nih.gov/health/topics/schizophrenia). *Health topics*. US [National Institute of Mental Health](https://en.wikipedia.org/wiki/National_Institute_of_Mental_Health "National Institute of Mental Health"). April 2022. Retrieved 22 August 2022.
4. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-SBU2012_4-0)**
["Medicinal treatment of psychosis/schizophrenia"](http://www.sbu.se/en/publications/sbu-assesses/schizophrenia--pharmacological-treatments-patient-involvement-and-organization-of-care/). [Swedish Agency for Health Technology Assessment and Assessment of Social Services](https://en.wikipedia.org/wiki/Swedish_Agency_for_Health_Technology_Assessment_and_Assessment_of_Social_Services "Swedish Agency for Health Technology Assessment and Assessment of Social Services") (SBU). 21 November 2012. [Archived](https://web.archive.org/web/20170629092226/http://www.sbu.se/en/publications/sbu-assesses/schizophrenia--pharmacological-treatments-patient-involvement-and-organization-of-care/) from the original on 29 June 2017. Retrieved 26 June 2017.
5. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-5)**
Proietto Sr J (November 2004). ["Diabetes and Antipsychotic Drugs"](https://www.medsafe.govt.nz/profs/puarticles/antipsychdiabetes.htm). [Medsafe](https://en.wikipedia.org/wiki/Medsafe "Medsafe").
6. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-6)**
Holt RI (September 2019). ["Association Between Antipsychotic Medication Use and Diabetes"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718373). *Current Diabetes Reports*. **19** (10) 96. [National Center for Biotechnology Information](https://en.wikipedia.org/wiki/National_Center_for_Biotechnology_Information "National Center for Biotechnology Information"). [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s11892-019-1220-8](https://doi.org/10.1007%2Fs11892-019-1220-8). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1534-4827](https://search.worldcat.org/issn/1534-4827). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6718373](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718373). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31478094](https://pubmed.ncbi.nlm.nih.gov/31478094).
7. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-3) [***e***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-4) [***f***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-5) [***g***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-6) [***h***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-7) [***i***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-8) [***j***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-9) [***k***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-10) [***l***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-11) [***m***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-12) [***n***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-13) [***o***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-14) [***p***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-15)
Owen MJ, Sawa A, Mortensen PB (July 2016). ["Schizophrenia"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940219). *The Lancet*. **388** (10039): 86–97\. [Bibcode](https://en.wikipedia.org/wiki/Bibcode_\(identifier\) "Bibcode (identifier)"):[2016Lanc..388...86O](https://ui.adsabs.harvard.edu/abs/2016Lanc..388...86O). [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S0140-6736(15)01121-6](https://doi.org/10.1016%2FS0140-6736%2815%2901121-6). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4940219](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940219). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [26777917](https://pubmed.ncbi.nlm.nih.gov/26777917).
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Sara G, Large M, Lappin J, Murrie B (May 2020). ["Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis"](https://academic.oup.com/schizophreniabulletin/article/46/3/505/5588638). *[Schizophrenia Bulletin](https://en.wikipedia.org/wiki/Schizophrenia_Bulletin "Schizophrenia Bulletin")*. **46** (3): 505–516\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1093/schbul/sbz102](https://doi.org/10.1093%2Fschbul%2Fsbz102). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7147575](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147575). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31618428](https://pubmed.ncbi.nlm.nih.gov/31618428).
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Gruebner O, Rapp MA, Adli M, Kluge U, Galea S, Heinz A (February 2017). ["Cities and Mental Health"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374256). *Deutsches Ärzteblatt International*. **114** (8): 121–127\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3238/arztebl.2017.0121](https://doi.org/10.3238%2Farztebl.2017.0121). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5374256](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374256). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [28302261](https://pubmed.ncbi.nlm.nih.gov/28302261).
10. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-3) [***e***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-4) [***f***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-5) [***g***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-6) [***h***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-7) [***i***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-8) [***j***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-9) [***k***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-10) [***l***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-11) [***m***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-12) [***n***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-13) [***o***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-14) [***p***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-15) [***q***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-16) [***r***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-17) [***s***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-18) [***t***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-19) [***u***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-20)
*Diagnostic and Statistical Manual of Mental Disorders: DSM-5* (5th ed.). Arlington, VA: American Psychiatric Association. 2013. pp. 99–105\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)")
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11. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Ferri2010_11-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Ferri2010_11-1)
Ferri FF (2010). "Chapter S". *Ferri's differential diagnosis: a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders* (2nd ed.). Philadelphia: Elsevier/Mosby. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)")
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12. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Paris2018_12-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Paris2018_12-1)
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14. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-3) [***e***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-4)
["Schizophrenia"](https://www.nimh.nih.gov/health/statistics/schizophrenia). *Statistics*. US [National Institute of Mental Health](https://en.wikipedia.org/wiki/National_Institute_of_Mental_Health "National Institute of Mental Health") (NIMH). 22 April 2022. Retrieved 23 August 2022.
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["Schizophrenia Fact Sheet and Information"](https://www.who.int/news-room/fact-sheets/detail/schizophrenia). [World Health Organization](https://en.wikipedia.org/wiki/World_Health_Organization "World Health Organization").
16. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-GBD2015_16-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-GBD2015_16-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-GBD2015_16-2)
Wang H, Naghavi M, Allen C, et al. (GBD 2015 Mortality and Causes of Death Collaborators) (October 2016). ["Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388903). *Lancet*. **388** (10053): 1459–1544\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S0140-6736(16)31012-1](https://doi.org/10.1016%2FS0140-6736%2816%2931012-1). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5388903](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388903). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [27733281](https://pubmed.ncbi.nlm.nih.gov/27733281).
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["ICD-11: 6A20 Schizophrenia"](https://icd.who.int/browse11/l-m/en#/http%3A%2F%2Fid.who.int%2Ficd%2Fentity%2F1683919430). [World Health Organization](https://en.wikipedia.org/wiki/World_Health_Organization "World Health Organization"). Retrieved 23 August 2022.
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Tramazzo S, Lian W, Ajnakina O, Carlson G, Bromet E, Kotov R, et al. (1 June 2024). ["Long-Term Course of Remission and Recovery in Psychotic Disorders"](https://osf.io/yh74r/). *American Journal of Psychiatry*. **181** (6): 532–540\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.ajp.20230189](https://doi.org/10.1176%2Fappi.ajp.20230189). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0002-953X](https://search.worldcat.org/issn/0002-953X). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38745457](https://pubmed.ncbi.nlm.nih.gov/38745457). Retrieved 23 May 2025.
19. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Ferri2019_19-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Ferri2019_19-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Ferri2019_19-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Ferri2019_19-3)
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20. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Javitt2014_20-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Javitt2014_20-1)
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Parakh P, Basu D (August 2013). "Cannabis and psychosis: have we found the missing links?". *[Asian Journal of Psychiatry](https://en.wikipedia.org/w/index.php?title=Asian_Journal_of_Psychiatry&action=edit&redlink=1 "Asian Journal of Psychiatry (page does not exist)")* (Review). **6** (4): 281–287\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.ajp.2013.03.012](https://doi.org/10.1016%2Fj.ajp.2013.03.012). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23810133](https://pubmed.ncbi.nlm.nih.gov/23810133). "Cannabis acts as a component cause of psychosis, that is, it increases the risk of psychosis in people with certain genetic or environmental vulnerabilities, though by itself, it is neither a sufficient nor a necessary cause of psychosis."
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Owen PR (July 2012). "Portrayals of schizophrenia by entertainment media: a content analysis of contemporary movies". *Psychiatr Serv*. **63** (7): 655–9\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.ps.201100371](https://doi.org/10.1176%2Fappi.ps.201100371). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22555313](https://pubmed.ncbi.nlm.nih.gov/22555313).
298. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-299)**
Katschnig H (October 2018). ["Psychiatry's contribution to the public stereotype of schizophrenia: Historical considerations"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174929). *J Eval Clin Pract*. **24** (5): 1093–1100\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/jep.13011](https://doi.org/10.1111%2Fjep.13011). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6174929](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174929). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [30112785](https://pubmed.ncbi.nlm.nih.gov/30112785).
299. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-300)**
Chen M, Lawrie S (December 2017). ["Newspaper depictions of mental and physical health"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709678). *BJPsych Bulletin*. **41** (6): 308–313\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1192/pb.bp.116.054775](https://doi.org/10.1192%2Fpb.bp.116.054775). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5709678](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709678). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29234506](https://pubmed.ncbi.nlm.nih.gov/29234506).
300. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-301)**
Dyga K, Stupak R (28 February 2018). ["Ways of understanding of religious delusions associated with a change of identity on the example of identification with Jesus Christ"](https://doi.org/10.12740%2FPP%2F64378). *Psychiatria Polska*. **52** (1): 69–80\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.12740/PP/64378](https://doi.org/10.12740%2FPP%2F64378). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29704415](https://pubmed.ncbi.nlm.nih.gov/29704415).
301. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-302)**
Dein S, Littlewood R (July 2011). "Religion and psychosis: a common evolutionary trajectory?". *Transcultural Psychiatry*. **48** (3): 318–335\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1177/1363461511402723](https://doi.org/10.1177%2F1363461511402723). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [21742955](https://pubmed.ncbi.nlm.nih.gov/21742955). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [12991391](https://api.semanticscholar.org/CorpusID:12991391).
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Dougall N, Maayan N, Soares-Weiser K, McDermott LM, McIntosh A (20 August 2015). ["Transcranial magnetic stimulation (TMS) for schizophrenia"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395125). *The Cochrane Database of Systematic Reviews*. **2015** (8) CD006081. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD006081.pub2](https://doi.org/10.1002%2F14651858.CD006081.pub2). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[1893/22520](https://hdl.handle.net/1893%2F22520). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9395125](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395125). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [26289586](https://pubmed.ncbi.nlm.nih.gov/26289586).
303. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Nathou2019_304-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Nathou2019_304-1)
Nathou C, Etard O, Dollfus S (2019). ["Auditory verbal hallucinations in schizophrenia: current perspectives in brain stimulation treatments"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662171). *Neuropsychiatric Disease and Treatment*. **15**: 2105–2117\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.2147/NDT.S168801](https://doi.org/10.2147%2FNDT.S168801). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6662171](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662171). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31413576](https://pubmed.ncbi.nlm.nih.gov/31413576).
304. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-305)**
Kraguljac NV, McDonald WM, Widge AS, Rodriguez CI, Tohen M, Nemeroff CB (January 2021). ["Neuroimaging Biomarkers in Schizophrenia"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222104). *Am J Psychiatry*. **178** (6): 509–521\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.ajp.2020.20030340](https://doi.org/10.1176%2Fappi.ajp.2020.20030340). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8222104](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222104). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33397140](https://pubmed.ncbi.nlm.nih.gov/33397140).
305. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-306)**
Khavari B, Cairns MJ (August 2020). ["Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463953). *Cells*. **9** (8): 1837. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3390/cells9081837](https://doi.org/10.3390%2Fcells9081837). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7463953](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463953). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32764320](https://pubmed.ncbi.nlm.nih.gov/32764320).
306. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-307)**
Goldsmith DR, Crooks CL, Walker EF, Cotes RO (April 2018). ["An Update on Promising Biomarkers in Schizophrenia"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526854). *Focus (American Psychiatric Publishing)*. **16** (2): 153–163\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.focus.20170046](https://doi.org/10.1176%2Fappi.focus.20170046). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6526854](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526854). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31975910](https://pubmed.ncbi.nlm.nih.gov/31975910).
307. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-308)**
Kumar S, Reddy PH (September 2016). ["Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343750). *Biochim Biophys Acta*. **1862** (9): 1617–1627\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.bbadis.2016.06.001](https://doi.org/10.1016%2Fj.bbadis.2016.06.001). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5343750](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343750). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [27264337](https://pubmed.ncbi.nlm.nih.gov/27264337).
308. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-309)**
van den Berg MM, Krauskopf J, Ramaekers JG, et al. (February 2020). ["Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders"](https://doi.org/10.1016%2Fj.pneurobio.2019.101732). *Prog Neurobiol*. **185** 101732. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.pneurobio.2019.101732](https://doi.org/10.1016%2Fj.pneurobio.2019.101732). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31816349](https://pubmed.ncbi.nlm.nih.gov/31816349). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [208790466](https://api.semanticscholar.org/CorpusID:208790466).
309. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-310)**
Palaniyappan L, Liddle PF (24 April 2013). ["Diagnostic Discontinuity in Psychosis: A Combined Study of Cortical Gyrification and Functional Connectivity"](https://academic.oup.com/schizophreniabulletin/article-abstract/40/3/675/1903745?redirectedFrom=fulltext). *Schizophrenia Bulletin*. **40** (3): 675–684\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1093/schbul/sbt050](https://doi.org/10.1093%2Fschbul%2Fsbt050). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1745-1701](https://search.worldcat.org/issn/1745-1701). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [3984507](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984507). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23615812](https://pubmed.ncbi.nlm.nih.gov/23615812).
## External links
- [Schizophrenia: Evolution and Synthesis](https://direct.mit.edu/books/oa-edited-volume/5036/SchizophreniaEvolution-and-Synthesis)
- [The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia, Third Edition](https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890424841)
| | |
|---|---|
| Classification | [D](https://www.wikidata.org/wiki/Q41112 "d:Q41112") **[ICD](https://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems "International Statistical Classification of Diseases and Related Health Problems")\-[11](https://en.wikipedia.org/wiki/ICD-11 "ICD-11")**: [6A20](https://icd.who.int/browse/latest-release/mms/en#1683919430) **[ICD](https://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems "International Statistical Classification of Diseases and Related Health Problems")\-[10](https://en.wikipedia.org/wiki/ICD-10 "ICD-10")**: [F20](https://icd.who.int/browse10/2019/en#/F20) **[ICD](https://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems "International Statistical Classification of Diseases and Related Health Problems")\-[9-CM](https://en.wikipedia.org/wiki/List_of_ICD-9_codes "List of ICD-9 codes")**: [295](http://www.icd9data.com/getICD9Code.ashx?icd9=295) **[OMIM](https://en.wikipedia.org/wiki/Online_Mendelian_Inheritance_in_Man "Online Mendelian Inheritance in Man")**: [181500](https://omim.org/entry/181500) **[MeSH](https://en.wikipedia.org/wiki/Medical_Subject_Headings "Medical Subject Headings")**: [D012559](https://meshb.nlm.nih.gov/record/ui?ui=D012559) **[DiseasesDB](https://en.wikipedia.org/wiki/Diseases_Database "Diseases Database")**: [11890](http://www.diseasesdatabase.com/ddb11890.htm) |
| External resources | **[MedlinePlus](https://en.wikipedia.org/wiki/MedlinePlus "MedlinePlus")**: [000928](https://www.nlm.nih.gov/medlineplus/ency/article/000928.htm) **[eMedicine](https://en.wikipedia.org/wiki/EMedicine "EMedicine")**: [med/2072](https://emedicine.medscape.com/med/2072-overview) [emerg/520](https://www.emedicine.com/emerg/topic520.htm) **[Patient UK](https://en.wikipedia.org/wiki/Patient_UK "Patient UK")**: [Schizophrenia](https://patient.info/doctor/schizophrenia-pro) **Scholia**: [Q41112](https://tools.wmflabs.org/scholia/topic/Q41112) |
| [v](https://en.wikipedia.org/wiki/Template:Schizophrenia "Template:Schizophrenia") [t](https://en.wikipedia.org/wiki/Template_talk:Schizophrenia "Template talk:Schizophrenia") [e](https://en.wikipedia.org/wiki/Special:EditPage/Template:Schizophrenia "Special:EditPage/Template:Schizophrenia")[Schizophrenia]() | |
|---|---|
| Causes and [risk factors](https://en.wikipedia.org/wiki/Risk_factors_of_schizophrenia "Risk factors of schizophrenia") | [17q12 microdeletion syndrome](https://en.wikipedia.org/wiki/17q12_microdeletion_syndrome "17q12 microdeletion syndrome") [Animal model of schizophrenia](https://en.wikipedia.org/wiki/Animal_model_of_schizophrenia "Animal model of schizophrenia") [Dopamine hypothesis of schizophrenia](https://en.wikipedia.org/wiki/Dopamine_hypothesis_of_schizophrenia "Dopamine hypothesis of schizophrenia") [Estrogen](https://en.wikipedia.org/wiki/Effects_of_estrogen_on_schizophrenia "Effects of estrogen on schizophrenia") [Epigenetics of schizophrenia](https://en.wikipedia.org/wiki/Epigenetics_of_schizophrenia "Epigenetics of schizophrenia") [Evolution of schizophrenia](https://en.wikipedia.org/wiki/Evolution_of_schizophrenia "Evolution of schizophrenia") [Evolutionary approaches to schizophrenia](https://en.wikipedia.org/wiki/Evolutionary_approaches_to_schizophrenia "Evolutionary approaches to schizophrenia") [Glutamate hypothesis of schizophrenia](https://en.wikipedia.org/wiki/Glutamate_hypothesis_of_schizophrenia "Glutamate hypothesis of schizophrenia") [Imprinted brain hypothesis](https://en.wikipedia.org/wiki/Imprinted_brain_hypothesis "Imprinted brain hypothesis") [Mechanisms of schizophrenia](https://en.wikipedia.org/wiki/Mechanisms_of_schizophrenia "Mechanisms of schizophrenia") [Sex differences in schizophrenia](https://en.wikipedia.org/wiki/Sex_differences_in_schizophrenia "Sex differences in schizophrenia") |
| [Diagnosis](https://en.wikipedia.org/wiki/Diagnosis_of_schizophrenia "Diagnosis of schizophrenia") and [management](https://en.wikipedia.org/wiki/Management_of_schizophrenia "Management of schizophrenia") | [Kiddie Schedule for Affective Disorders and Schizophrenia](https://en.wikipedia.org/wiki/Kiddie_Schedule_for_Affective_Disorders_and_Schizophrenia "Kiddie Schedule for Affective Disorders and Schizophrenia") [LY-404,039](https://en.wikipedia.org/wiki/LY-404,039 "LY-404,039") [Metacognitive training](https://en.wikipedia.org/wiki/Metacognitive_training "Metacognitive training") [Positive and Negative Syndrome Scale](https://en.wikipedia.org/wiki/Positive_and_Negative_Syndrome_Scale "Positive and Negative Syndrome Scale") [Schizophrenia Research Foundation](https://en.wikipedia.org/wiki/Schizophrenia_Research_Foundation "Schizophrenia Research Foundation") |
| [Symptoms](https://en.wikipedia.org/wiki/Basic_symptoms_of_schizophrenia "Basic symptoms of schizophrenia") and [prognosis](https://en.wikipedia.org/wiki/Prognosis_of_schizophrenia "Prognosis of schizophrenia") | [Oneiroid syndrome](https://en.wikipedia.org/wiki/Oneiroid_syndrome "Oneiroid syndrome") [Physical health in schizophrenia](https://en.wikipedia.org/wiki/Physical_health_in_schizophrenia "Physical health in schizophrenia") [Post-schizophrenic depression](https://en.wikipedia.org/wiki/Post-schizophrenic_depression "Post-schizophrenic depression") [Primary polydipsia](https://en.wikipedia.org/wiki/Primary_polydipsia "Primary polydipsia") [Visual processing abnormalities in schizophrenia](https://en.wikipedia.org/wiki/Visual_processing_abnormalities_in_schizophrenia "Visual processing abnormalities in schizophrenia") [Self-disorder](https://en.wikipedia.org/wiki/Self-disorder "Self-disorder") |
| Types | [Childhood schizophrenia](https://en.wikipedia.org/wiki/Childhood_schizophrenia "Childhood schizophrenia") [Disorganized schizophrenia](https://en.wikipedia.org/wiki/Disorganized_schizophrenia "Disorganized schizophrenia") [Kandinsky–Clérambault syndrome](https://en.wikipedia.org/wiki/Kandinsky%E2%80%93Cl%C3%A9rambault_syndrome "Kandinsky–Clérambault syndrome") [Pseudoneurotic schizophrenia](https://en.wikipedia.org/wiki/Pseudoneurotic_schizophrenia "Pseudoneurotic schizophrenia") [Simple-type schizophrenia](https://en.wikipedia.org/wiki/Simple-type_schizophrenia "Simple-type schizophrenia") [Catatonic schizophrenia](https://en.wikipedia.org/wiki/Catatonic_schizophrenia "Catatonic schizophrenia") |
| [History](https://en.wikipedia.org/wiki/History_of_schizophrenia "History of schizophrenia") | [Dementia praecox](https://en.wikipedia.org/wiki/Dementia_praecox "Dementia praecox") [Insulin shock therapy](https://en.wikipedia.org/wiki/Insulin_shock_therapy "Insulin shock therapy") [Montreal experiments](https://en.wikipedia.org/wiki/Montreal_experiments "Montreal experiments") *[Colorado v. Connelly](https://en.wikipedia.org/wiki/Colorado_v._Connelly "Colorado v. Connelly")* |
| Comparisons and relationships | [Bipolar disorder](https://en.wikipedia.org/w/index.php?title=Comparison_of_bipolar_disorder_and_schizophrenia&action=edit&redlink=1 "Comparison of bipolar disorder and schizophrenia (page does not exist)") [Religion and schizophrenia](https://en.wikipedia.org/wiki/Religion_and_schizophrenia "Religion and schizophrenia") [Schizophrenia and tobacco smoking](https://en.wikipedia.org/wiki/Schizophrenia_and_tobacco_smoking "Schizophrenia and tobacco smoking") [Schizotypy](https://en.wikipedia.org/wiki/Schizotypy "Schizotypy") [Schizophrenia spectrum](https://en.wikipedia.org/wiki/Schizophrenia_spectrum "Schizophrenia spectrum") |
|  [Category](https://en.wikipedia.org/wiki/Category:Schizophrenia "Category:Schizophrenia") | |
| [v](https://en.wikipedia.org/wiki/Template:Mental_disorders "Template:Mental disorders") [t](https://en.wikipedia.org/wiki/Template_talk:Mental_disorders "Template talk:Mental disorders") [e](https://en.wikipedia.org/wiki/Special:EditPage/Template:Mental_disorders "Special:EditPage/Template:Mental disorders")[Mental disorders](https://en.wikipedia.org/wiki/Mental_disorder "Mental disorder") ([Classification](https://en.wikipedia.org/wiki/Classification_of_mental_disorders "Classification of mental disorders")) | |
|---|---|
| Adult personality and behavior | |
| | |
| Sexual | [Ego-dystonic sexual orientation](https://en.wikipedia.org/wiki/Ego-dystonic_sexual_orientation "Ego-dystonic sexual orientation") [Paraphilia](https://en.wikipedia.org/wiki/Paraphilia "Paraphilia") [Fetishism](https://en.wikipedia.org/wiki/Sexual_fetishism "Sexual fetishism") [Voyeurism](https://en.wikipedia.org/wiki/Voyeurism "Voyeurism") [Sexual anhedonia](https://en.wikipedia.org/wiki/Sexual_anhedonia "Sexual anhedonia") [Sexual anorexia](https://en.wikipedia.org/wiki/Sexual_anorexia "Sexual anorexia") [Sexual maturation disorder](https://en.wikipedia.org/wiki/Sexual_maturation_disorder "Sexual maturation disorder") [Sexual relationship disorder](https://en.wikipedia.org/wiki/Sexual_relationship_disorder "Sexual relationship disorder") [Compulsive sexual behaviour disorder](https://en.wikipedia.org/wiki/Compulsive_sexual_behaviour_disorder "Compulsive sexual behaviour disorder") |
| Other | [Factitious disorder](https://en.wikipedia.org/wiki/Factitious_disorder "Factitious disorder") [Munchausen syndrome](https://en.wikipedia.org/wiki/Factitious_disorder_imposed_on_self "Factitious disorder imposed on self") [Fear of intimacy](https://en.wikipedia.org/wiki/Fear_of_intimacy "Fear of intimacy") [Gender dysphoria](https://en.wikipedia.org/wiki/Gender_dysphoria "Gender dysphoria") [Intermittent explosive disorder](https://en.wikipedia.org/wiki/Intermittent_explosive_disorder "Intermittent explosive disorder") [Dermatillomania](https://en.wikipedia.org/wiki/Excoriation_disorder "Excoriation disorder") [Kleptomania](https://en.wikipedia.org/wiki/Kleptomania "Kleptomania") [Pyromania](https://en.wikipedia.org/wiki/Pyromania "Pyromania") [Trichotillomania](https://en.wikipedia.org/wiki/Trichotillomania "Trichotillomania") [Personality disorder](https://en.wikipedia.org/wiki/Personality_disorder "Personality disorder") |
| [Childhood and learning](https://en.wikipedia.org/wiki/Mental_disorders_diagnosed_in_childhood "Mental disorders diagnosed in childhood") | |
| | |
| [Emotional and behavioral](https://en.wikipedia.org/wiki/Emotional_and_behavioral_disorders "Emotional and behavioral disorders") | [ADHD](https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder "Attention deficit hyperactivity disorder") [Conduct disorder](https://en.wikipedia.org/wiki/Conduct_disorder "Conduct disorder") [ODD](https://en.wikipedia.org/wiki/Oppositional_defiant_disorder "Oppositional defiant disorder") [Emotional and behavioral disorders](https://en.wikipedia.org/wiki/Emotional_and_behavioral_disorders "Emotional and behavioral disorders") [Separation anxiety disorder](https://en.wikipedia.org/wiki/Separation_anxiety_disorder "Separation anxiety disorder") [Movement disorders](https://en.wikipedia.org/wiki/Movement_disorders "Movement disorders") [Stereotypic](https://en.wikipedia.org/wiki/Stereotypic_movement_disorder "Stereotypic movement disorder") Social functioning [DAD](https://en.wikipedia.org/wiki/Disinhibited_attachment_disorder "Disinhibited attachment disorder") [RAD](https://en.wikipedia.org/wiki/Reactive_attachment_disorder "Reactive attachment disorder") [Selective mutism](https://en.wikipedia.org/wiki/Selective_mutism "Selective mutism") [Speech](https://en.wikipedia.org/wiki/Speech_disorder "Speech disorder") [Cluttering](https://en.wikipedia.org/wiki/Cluttering "Cluttering") [Stuttering](https://en.wikipedia.org/wiki/Stuttering "Stuttering") [Tic disorder](https://en.wikipedia.org/wiki/Tic_disorder "Tic disorder") [Tourette syndrome](https://en.wikipedia.org/wiki/Tourette_syndrome "Tourette syndrome") |
| [Intellectual disability](https://en.wikipedia.org/wiki/Intellectual_disability "Intellectual disability") | [X-linked intellectual disability](https://en.wikipedia.org/wiki/X-linked_intellectual_disability "X-linked intellectual disability") [Lujan–Fryns syndrome](https://en.wikipedia.org/wiki/Lujan%E2%80%93Fryns_syndrome "Lujan–Fryns syndrome") |
| Psychological development ([developmental disabilities](https://en.wikipedia.org/wiki/Developmental_disability "Developmental disability")) | [Pervasive](https://en.wikipedia.org/wiki/Pervasive_developmental_disorder "Pervasive developmental disorder") [Specific](https://en.wikipedia.org/wiki/Specific_developmental_disorder "Specific developmental disorder") |
| [Mood](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder") (affective) | |
| [Bipolar](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder") [Bipolar I](https://en.wikipedia.org/wiki/Bipolar_I_disorder "Bipolar I disorder") [Bipolar II](https://en.wikipedia.org/wiki/Bipolar_II_disorder "Bipolar II disorder") [Bipolar NOS](https://en.wikipedia.org/wiki/Bipolar_disorder_not_otherwise_specified "Bipolar disorder not otherwise specified") [Cyclothymia](https://en.wikipedia.org/wiki/Cyclothymia "Cyclothymia") [Depression](https://en.wikipedia.org/wiki/Depression_\(mood\) "Depression (mood)") [Atypical depression](https://en.wikipedia.org/wiki/Atypical_depression "Atypical depression") [Dysthymia](https://en.wikipedia.org/wiki/Dysthymia "Dysthymia") [Major depressive disorder](https://en.wikipedia.org/wiki/Major_depressive_disorder "Major depressive disorder") [Melancholic depression](https://en.wikipedia.org/wiki/Melancholic_depression "Melancholic depression") [Seasonal affective disorder](https://en.wikipedia.org/wiki/Seasonal_affective_disorder "Seasonal affective disorder") [Mania](https://en.wikipedia.org/wiki/Mania "Mania") | |
| Neurological and symptomatic | |
| | |
| [Autism spectrum](https://en.wikipedia.org/wiki/Autism_spectrum "Autism spectrum") | [Autism](https://en.wikipedia.org/wiki/Autism "Autism") [Asperger syndrome](https://en.wikipedia.org/wiki/Asperger_syndrome "Asperger syndrome") [High-functioning autism](https://en.wikipedia.org/wiki/High-functioning_autism "High-functioning autism") [PDD-NOS](https://en.wikipedia.org/wiki/Pervasive_developmental_disorder_not_otherwise_specified "Pervasive developmental disorder not otherwise specified") [Savant syndrome](https://en.wikipedia.org/wiki/Savant_syndrome "Savant syndrome") |
| [Dementia](https://en.wikipedia.org/wiki/Dementia "Dementia") | [AIDS dementia complex](https://en.wikipedia.org/wiki/HIV-associated_neurocognitive_disorder "HIV-associated neurocognitive disorder") [Alzheimer's disease](https://en.wikipedia.org/wiki/Alzheimer%27s_disease "Alzheimer's disease") [Creutzfeldt–Jakob disease](https://en.wikipedia.org/wiki/Creutzfeldt%E2%80%93Jakob_disease "Creutzfeldt–Jakob disease") [Frontotemporal dementia](https://en.wikipedia.org/wiki/Frontotemporal_dementia "Frontotemporal dementia") [Huntington's disease](https://en.wikipedia.org/wiki/Huntington%27s_disease "Huntington's disease") [Mild cognitive impairment](https://en.wikipedia.org/wiki/Mild_cognitive_impairment "Mild cognitive impairment") [Parkinson's disease](https://en.wikipedia.org/wiki/Parkinson%27s_disease "Parkinson's disease") [Pick's disease](https://en.wikipedia.org/wiki/Pick%27s_disease "Pick's disease") [Sundowning](https://en.wikipedia.org/wiki/Sundowning "Sundowning") [Vascular dementia](https://en.wikipedia.org/wiki/Vascular_dementia "Vascular dementia") [Wandering](https://en.wikipedia.org/wiki/Wandering_\(dementia\) "Wandering (dementia)") |
| Other | [Delirium](https://en.wikipedia.org/wiki/Delirium "Delirium") [Organic brain syndrome](https://en.wikipedia.org/wiki/Organic_brain_syndrome "Organic brain syndrome") [Post-concussion syndrome](https://en.wikipedia.org/wiki/Post-concussion_syndrome "Post-concussion syndrome") |
| [Neurotic](https://en.wikipedia.org/wiki/Neurosis "Neurosis"), [stress](https://en.wikipedia.org/wiki/Stress_\(biology\) "Stress (biology)")\-related and [somatoform](https://en.wikipedia.org/wiki/Somatic_symptom_disorder "Somatic symptom disorder") | |
| | |
| [Adjustment](https://en.wikipedia.org/wiki/Adjustment_disorder "Adjustment disorder") | [Adjustment disorder](https://en.wikipedia.org/wiki/Adjustment_disorder "Adjustment disorder") with depressed mood |
| [Anxiety](https://en.wikipedia.org/wiki/Anxiety_disorder "Anxiety disorder") | |
| | |
| [Phobia](https://en.wikipedia.org/wiki/Phobia "Phobia") | [Agoraphobia](https://en.wikipedia.org/wiki/Agoraphobia "Agoraphobia") [Childhood phobia](https://en.wikipedia.org/wiki/Childhood_phobia "Childhood phobia") [Social anxiety](https://en.wikipedia.org/wiki/Social_anxiety "Social anxiety") [Social phobia](https://en.wikipedia.org/wiki/Social_anxiety_disorder "Social anxiety disorder") [Anthropophobia](https://en.wikipedia.org/wiki/Anthropophobia "Anthropophobia") [Specific social phobia](https://en.wikipedia.org/wiki/Specific_social_phobia "Specific social phobia") [Specific phobia](https://en.wikipedia.org/wiki/Specific_phobia "Specific phobia") [Claustrophobia](https://en.wikipedia.org/wiki/Claustrophobia "Claustrophobia") |
| Other | [Generalized anxiety disorder](https://en.wikipedia.org/wiki/Generalized_anxiety_disorder "Generalized anxiety disorder") [OCD](https://en.wikipedia.org/wiki/Obsessive%E2%80%93compulsive_disorder "Obsessive–compulsive disorder") [Panic attack](https://en.wikipedia.org/wiki/Panic_attack "Panic attack") [Panic disorder](https://en.wikipedia.org/wiki/Panic_disorder "Panic disorder") [Paranoia](https://en.wikipedia.org/wiki/Paranoia "Paranoia") [Stress](https://en.wikipedia.org/wiki/Psychological_stress "Psychological stress") [Acute stress reaction](https://en.wikipedia.org/wiki/Acute_stress_reaction "Acute stress reaction") [PTSD](https://en.wikipedia.org/wiki/Post-traumatic_stress_disorder "Post-traumatic stress disorder") |
| [Dissociative](https://en.wikipedia.org/wiki/Dissociative_disorder "Dissociative disorder") | [Depersonalization-derealization disorder](https://en.wikipedia.org/wiki/Depersonalization-derealization_disorder "Depersonalization-derealization disorder") [Dissociative identity disorder](https://en.wikipedia.org/wiki/Dissociative_identity_disorder "Dissociative identity disorder") [Dissociative amnesia](https://en.wikipedia.org/wiki/Dissociative_amnesia "Dissociative amnesia") [Dissociative fugue](https://en.wikipedia.org/wiki/Dissociative_fugue "Dissociative fugue") [Dissociative disorder not otherwise specified](https://en.wikipedia.org/wiki/Dissociative_disorder_not_otherwise_specified "Dissociative disorder not otherwise specified") [Other specified dissociative disorder](https://en.wikipedia.org/wiki/Other_specified_dissociative_disorder "Other specified dissociative disorder") |
| [Somatic symptom](https://en.wikipedia.org/wiki/Somatic_symptom_disorder "Somatic symptom disorder") | [Body dysmorphic disorder](https://en.wikipedia.org/wiki/Body_dysmorphic_disorder "Body dysmorphic disorder") [Conversion disorder](https://en.wikipedia.org/wiki/Conversion_disorder "Conversion disorder") [Ganser syndrome](https://en.wikipedia.org/wiki/Ganser_syndrome "Ganser syndrome") [Globus pharyngeus](https://en.wikipedia.org/wiki/Globus_pharyngeus "Globus pharyngeus") [Psychogenic non-epileptic seizures](https://en.wikipedia.org/wiki/Psychogenic_non-epileptic_seizure "Psychogenic non-epileptic seizure") [False pregnancy](https://en.wikipedia.org/wiki/False_pregnancy "False pregnancy") [Hypochondriasis](https://en.wikipedia.org/wiki/Hypochondriasis "Hypochondriasis") [Mass psychogenic illness](https://en.wikipedia.org/wiki/Mass_psychogenic_illness "Mass psychogenic illness") [Nosophobia](https://en.wikipedia.org/wiki/Nosophobia "Nosophobia") [Psychogenic pain](https://en.wikipedia.org/wiki/Psychogenic_pain "Psychogenic pain") |
| Physiological and physical behavior | |
| | |
| [Eating](https://en.wikipedia.org/wiki/Eating_disorder "Eating disorder") | [Anorexia nervosa](https://en.wikipedia.org/wiki/Anorexia_nervosa "Anorexia nervosa") [Bulimia nervosa](https://en.wikipedia.org/wiki/Bulimia_nervosa "Bulimia nervosa") [Binge eating disorder](https://en.wikipedia.org/wiki/Binge_eating_disorder "Binge eating disorder") [Avoidant/restrictive food intake disorder](https://en.wikipedia.org/wiki/Avoidant/restrictive_food_intake_disorder "Avoidant/restrictive food intake disorder") [Pica](https://en.wikipedia.org/wiki/Pica_\(disorder\) "Pica (disorder)") [Rumination syndrome](https://en.wikipedia.org/wiki/Rumination_syndrome "Rumination syndrome") [Other specified feeding or eating disorder](https://en.wikipedia.org/wiki/Other_specified_feeding_or_eating_disorder "Other specified feeding or eating disorder") |
| Nonorganic [sleep](https://en.wikipedia.org/wiki/Sleep_disorder "Sleep disorder") | [Hypersomnia](https://en.wikipedia.org/wiki/Hypersomnia "Hypersomnia") [Insomnia](https://en.wikipedia.org/wiki/Insomnia "Insomnia") [Parasomnia](https://en.wikipedia.org/wiki/Parasomnia "Parasomnia") [Night terror](https://en.wikipedia.org/wiki/Night_terror "Night terror") [Nightmare](https://en.wikipedia.org/wiki/Nightmare "Nightmare") [REM sleep behavior disorder](https://en.wikipedia.org/wiki/Rapid_eye_movement_sleep_behavior_disorder "Rapid eye movement sleep behavior disorder") |
| [Postnatal](https://en.wikipedia.org/wiki/Psychiatric_disorders_of_childbirth "Psychiatric disorders of childbirth") | [Postpartum depression](https://en.wikipedia.org/wiki/Postpartum_depression "Postpartum depression") [Postpartum psychosis](https://en.wikipedia.org/wiki/Postpartum_psychosis "Postpartum psychosis") |
| [Sexual desire](https://en.wikipedia.org/wiki/Sexual_dysfunction#Sexual_desire_disorders "Sexual dysfunction") | [Hypersexuality](https://en.wikipedia.org/wiki/Hypersexuality "Hypersexuality") [Hypoactive sexual desire disorder](https://en.wikipedia.org/wiki/Hypoactive_sexual_desire_disorder "Hypoactive sexual desire disorder") |
| [Psychoactive](https://en.wikipedia.org/wiki/Psychoactive_drug "Psychoactive drug") substances, [substance abuse](https://en.wikipedia.org/wiki/Substance_abuse "Substance abuse") and substance-related | |
| [Drug overdose](https://en.wikipedia.org/wiki/Drug_overdose "Drug overdose") [Hallucinogen persisting perception disorder](https://en.wikipedia.org/wiki/Hallucinogen_persisting_perception_disorder "Hallucinogen persisting perception disorder") [Intoxication](https://en.wikipedia.org/wiki/Substance_intoxication "Substance intoxication") [Physical dependence](https://en.wikipedia.org/wiki/Physical_dependence "Physical dependence") [Rebound effect](https://en.wikipedia.org/wiki/Rebound_effect "Rebound effect") [Stimulant psychosis](https://en.wikipedia.org/wiki/Stimulant_psychosis "Stimulant psychosis") [Substance dependence](https://en.wikipedia.org/wiki/Substance_dependence "Substance dependence") [Substance-induced psychosis](https://en.wikipedia.org/wiki/Substance-induced_psychosis "Substance-induced psychosis") [Withdrawal](https://en.wikipedia.org/wiki/Drug_withdrawal "Drug withdrawal") | |
| [Schizophrenia](), [schizotypal](https://en.wikipedia.org/wiki/Schizotypal_personality_disorder "Schizotypal personality disorder") and [delusional](https://en.wikipedia.org/wiki/Delusional_disorder "Delusional disorder") | |
| | |
| Delusional | [Delusional disorder](https://en.wikipedia.org/wiki/Delusional_disorder "Delusional disorder") [Folie à deux](https://en.wikipedia.org/wiki/Folie_%C3%A0_deux "Folie à deux") |
| [Psychosis](https://en.wikipedia.org/wiki/Psychosis "Psychosis") and schizophrenia-like | [Brief reactive psychosis](https://en.wikipedia.org/wiki/Brief_reactive_psychosis "Brief reactive psychosis") [Schizoaffective disorder](https://en.wikipedia.org/wiki/Schizoaffective_disorder "Schizoaffective disorder") [Schizophreniform disorder](https://en.wikipedia.org/wiki/Schizophreniform_disorder "Schizophreniform disorder") |
| Schizophrenia | [Childhood schizophrenia](https://en.wikipedia.org/wiki/Childhood_schizophrenia "Childhood schizophrenia") [Disorganized (hebephrenic) schizophrenia](https://en.wikipedia.org/wiki/Disorganized_schizophrenia "Disorganized schizophrenia") [Pseudoneurotic schizophrenia](https://en.wikipedia.org/wiki/Pseudoneurotic_schizophrenia "Pseudoneurotic schizophrenia") [Simple-type schizophrenia](https://en.wikipedia.org/wiki/Simple-type_schizophrenia "Simple-type schizophrenia") |
| Other | [Catatonia](https://en.wikipedia.org/wiki/Catatonia "Catatonia") |
| Symptoms and uncategorized | |
| [Impulse-control disorder](https://en.wikipedia.org/wiki/Impulse-control_disorder "Impulse-control disorder") [Klüver–Bucy syndrome](https://en.wikipedia.org/wiki/Kl%C3%BCver%E2%80%93Bucy_syndrome "Klüver–Bucy syndrome") [Psychomotor agitation](https://en.wikipedia.org/wiki/Psychomotor_agitation "Psychomotor agitation") [Stereotypy](https://en.wikipedia.org/wiki/Stereotypy "Stereotypy") [Caregiver burden](https://en.wikipedia.org/wiki/Caregiver_burden "Caregiver burden") | |
|  [Category](https://en.wikipedia.org/wiki/Category:Mental_disorders "Category:Mental disorders") | |
[Portals](https://en.wikipedia.org/wiki/Wikipedia:Contents/Portals "Wikipedia:Contents/Portals"):
- [](https://en.wikipedia.org/wiki/File:Psi_and_Caduceus.svg) [Psychiatry](https://en.wikipedia.org/wiki/Portal:Psychiatry "Portal:Psychiatry")
-  [Psychology](https://en.wikipedia.org/wiki/Portal:Psychology "Portal:Psychology")
**Schizophrenia** at Wikipedia's [sister projects](https://en.wikipedia.org/wiki/Wikipedia:Wikimedia_sister_projects "Wikipedia:Wikimedia sister projects"):
- [](https://en.wikipedia.org/wiki/File:Wiktionary-logo-en-v2.svg)[**Definitions**](https://en.wiktionary.org/wiki/Special:Search/Schizophrenia "wikt:Special:Search/Schizophrenia") from Wiktionary
- [](https://en.wikipedia.org/wiki/File:Commons-logo.svg)[**Media**](https://commons.wikimedia.org/wiki/Category:Schizophrenia "c:Category:Schizophrenia") from Commons
- [](https://en.wikipedia.org/wiki/File:Wikinews-logo.svg)[**News**](https://en.wikinews.org/wiki/Category:Schizophrenia "n:Category:Schizophrenia") from Wikinews
- [**Quotations**](https://en.wikiquote.org/wiki/Schizophrenia "q:Schizophrenia") from Wikiquote
- [**Data**](https://www.wikidata.org/wiki/Q41112 "d:Q41112") from Wikidata
| [Authority control databases](https://en.wikipedia.org/wiki/Help:Authority_control "Help:Authority control") [](https://www.wikidata.org/wiki/Q41112#identifiers "Edit this at Wikidata") | |
|---|---|
| International | [GND](https://d-nb.info/gnd/4052527-2) |
| National | [United States](https://id.loc.gov/authorities/sh85118162) [France](https://catalogue.bnf.fr/ark:/12148/cb119458692) [BnF data](https://data.bnf.fr/ark:/12148/cb119458692) [Japan](https://id.ndl.go.jp/auth/ndlna/00570393) [Czech Republic](https://aleph.nkp.cz/F/?func=find-c&local_base=aut&ccl_term=ica=ph125438&CON_LNG=ENG) [Israel](https://www.nli.org.il/en/authorities/987007560704805171) |
| Other | [Yale LUX](https://lux.collections.yale.edu/view/concept/37238dda-85f2-40e1-b1ff-8aef561d53a2) |
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Schizophrenia
105 languages
[Add topic](https://en.wikipedia.org/wiki/Schizophrenia) |
| Readable Markdown | | Schizophrenia | |
|---|---|
| [](https://en.wikipedia.org/wiki/File:Cloth_embroidered_by_a_schizophrenia_sufferer.jpg) | |
| Cloth [embroidered](https://en.wikipedia.org/wiki/Embroidered "Embroidered") by a person diagnosed with schizophrenia | |
| Pronunciation | [*SKIT\-sə-FREE\-nee-ə*](https://en.wikipedia.org/wiki/Help:Pronunciation_respelling_key "Help:Pronunciation respelling key"), [*SKIT\-sə-FREN\-ee-ə*](https://en.wikipedia.org/wiki/Help:Pronunciation_respelling_key "Help:Pronunciation respelling key") |
| [Specialty](https://en.wikipedia.org/wiki/Medical_specialty "Medical specialty") | [Psychiatry](https://en.wikipedia.org/wiki/Psychiatry "Psychiatry")[\[1\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-1) |
| [Symptoms](https://en.wikipedia.org/wiki/Signs_and_symptoms "Signs and symptoms") | [Hallucinations](https://en.wikipedia.org/wiki/Hallucination "Hallucination"), [delusions](https://en.wikipedia.org/wiki/Delusion "Delusion"), [disorganized thinking](https://en.wikipedia.org/wiki/Thought_disorder "Thought disorder") or behavior, [flat](https://en.wikipedia.org/wiki/Reduced_affect_display "Reduced affect display") or [inappropriate affect](https://en.wikipedia.org/wiki/Inappropriate_affect "Inappropriate affect")[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2)[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3) |
| [Complications](https://en.wikipedia.org/wiki/Complication_\(medicine\) "Complication (medicine)") | Harm to self or others, [social isolation](https://en.wikipedia.org/wiki/Social_isolation "Social isolation"), [heart disease](https://en.wikipedia.org/wiki/Cardiovascular_disease "Cardiovascular disease"), [suicide](https://en.wikipedia.org/wiki/Suicide "Suicide"), [lifestyle diseases](https://en.wikipedia.org/wiki/Lifestyle_disease "Lifestyle disease"),[\[4\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-SBU2012-4) [obesity](https://en.wikipedia.org/wiki/Obesity "Obesity") and [type 2 diabetes](https://en.wikipedia.org/wiki/Type_2_diabetes "Type 2 diabetes") arising from [antipsychotic](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic") medication[\[5\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-5)[\[6\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-6) |
| Usual onset | Ages 16 to 30[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3) |
| Duration | Chronic[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3) |
| [Causes](https://en.wikipedia.org/wiki/Cause_\(medicine\) "Cause (medicine)") | Environmental and genetic factors[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) |
| [Risk factors](https://en.wikipedia.org/wiki/Risk_factor "Risk factor") | [Family history](https://en.wikipedia.org/wiki/Family_history_\(medicine\) "Family history (medicine)"), [cannabis](https://en.wikipedia.org/wiki/Cannabis_\(drug\) "Cannabis (drug)") use in adolescence, [hallucinogen](https://en.wikipedia.org/wiki/Hallucinogen "Hallucinogen")\- or [amphetamine](https://en.wikipedia.org/wiki/Amphetamine "Amphetamine")\-associated psychosis,[\[8\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-8) problems during pregnancy, [childhood adversity](https://en.wikipedia.org/wiki/Adverse_childhood_experiences "Adverse childhood experiences"), being born or raised in a city[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)[\[9\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-9) |
| [Diagnostic method](https://en.wikipedia.org/wiki/Medical_diagnosis "Medical diagnosis") | Based on observed behavior, reported experiences, and reports of others familiar with the person[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) |
| [Differential diagnosis](https://en.wikipedia.org/wiki/Differential_diagnosis "Differential diagnosis") | [Substance use disorder](https://en.wikipedia.org/wiki/Substance_use_disorder "Substance use disorder"), [Huntington's disease](https://en.wikipedia.org/wiki/Huntington%27s_disease "Huntington's disease"), [mood disorders](https://en.wikipedia.org/wiki/Mood_disorders "Mood disorders") ([bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder"), [major depressive disorder](https://en.wikipedia.org/wiki/Major_depressive_disorder "Major depressive disorder")), [autism](https://en.wikipedia.org/wiki/Autism "Autism"),[\[11\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2010-11) [borderline personality disorder](https://en.wikipedia.org/wiki/Borderline_personality_disorder "Borderline personality disorder"),[\[12\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Paris2018-12) [schizophreniform disorder](https://en.wikipedia.org/wiki/Schizophreniform_disorder "Schizophreniform disorder"), [schizotypal personality disorder](https://en.wikipedia.org/wiki/Schizotypal_personality_disorder "Schizotypal personality disorder"), [schizoid personality disorder](https://en.wikipedia.org/wiki/Schizoid_personality_disorder "Schizoid personality disorder"), [antisocial personality disorder](https://en.wikipedia.org/wiki/Antisocial_personality_disorder "Antisocial personality disorder"), [psychotic depression](https://en.wikipedia.org/wiki/Psychotic_depression "Psychotic depression"), [anxiety](https://en.wikipedia.org/wiki/Anxiety "Anxiety"), [disruptive mood dysregulation disorder](https://en.wikipedia.org/wiki/Disruptive_mood_dysregulation_disorder "Disruptive mood dysregulation disorder"), [sleep paralysis](https://en.wikipedia.org/wiki/Sleep_paralysis "Sleep paralysis") |
| Management | Counseling, [life skills](https://en.wikipedia.org/wiki/Life_skills "Life skills") training[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2)[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) |
| [Medication](https://en.wikipedia.org/wiki/Medication "Medication") | [Antipsychotics](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic")[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) |
| [Prognosis](https://en.wikipedia.org/wiki/Prognosis "Prognosis") | 20–28 years shorter [life expectancy](https://en.wikipedia.org/wiki/Life_expectancy "Life expectancy")[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13)[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) |
| Frequency | ~0.32% (1 in 300) of the global population is affected[\[15\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO_FACT_SHEET-15) |
| Deaths | ~17,000 (2015)[\[16\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2015-16) |
**Schizophrenia** is a [mental disorder](https://en.wikipedia.org/wiki/Mental_disorder "Mental disorder")[\[17\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-17)[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) characterized variously by [hallucinations](https://en.wikipedia.org/wiki/Hallucination "Hallucination") (typically, [hearing voices](https://en.wikipedia.org/wiki/Auditory_hallucination#Schizophrenia "Auditory hallucination")), [delusions](https://en.wikipedia.org/wiki/Delusion "Delusion"), [disorganized thinking](https://en.wikipedia.org/wiki/Thought_disorder "Thought disorder") or behavior,[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) and [flat](https://en.wikipedia.org/wiki/Reduced_affect_display "Reduced affect display") or [inappropriate affect](https://en.wikipedia.org/wiki/Inappropriate_affect "Inappropriate affect").[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) Symptoms [develop gradually](https://en.wikipedia.org/wiki/Prodrome "Prodrome") and typically begin during young adulthood and rarely resolve.[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3)[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[18\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-18) There is no objective diagnostic test; diagnosis is based on observed behavior, a [psychiatric history](https://en.wikipedia.org/wiki/Psychiatric_history "Psychiatric history") that includes the person's reported experiences, and reports of others familiar with the person.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) For a [formal diagnosis](https://en.wikipedia.org/wiki/Diagnosis_of_schizophrenia "Diagnosis of schizophrenia"), the described symptoms need to have been present for at least six months (according to the [DSM-5](https://en.wikipedia.org/wiki/DSM-5 "DSM-5")) or one month (according to the [ICD-11](https://en.wikipedia.org/wiki/ICD-11 "ICD-11")).[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[19\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2019-19) Many people with schizophrenia have other mental disorders, especially [mood](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder"), [anxiety](https://en.wikipedia.org/wiki/Anxiety_disorder "Anxiety disorder"), and [substance use](https://en.wikipedia.org/wiki/Substance_use_disorder "Substance use disorder") disorders, as well as [obsessive–compulsive disorder](https://en.wikipedia.org/wiki/Obsessive%E2%80%93compulsive_disorder "Obsessive–compulsive disorder") (OCD).[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)
The [lifetime prevalence](https://en.wikipedia.org/wiki/Lifetime_prevalence "Lifetime prevalence") of developing schizophrenia is about 0.3% to 0.7%.[\[20\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Javitt2014-20) In 2017, there were an estimated 1.1 million new cases and in 2022 a total of 24 million cases globally.[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2)[\[21\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2018-21) Males are more often affected and on average have an earlier onset than females.[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2) The causes of schizophrenia may include [genetic](https://en.wikipedia.org/wiki/Heredity "Heredity") and [environmental](https://en.wikipedia.org/wiki/Environmental_factor "Environmental factor") factors.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) Genetic factors include a variety of common and rare [genetic variants](https://en.wikipedia.org/wiki/Human_genetic_variation "Human genetic variation").[\[22\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-vandeLeemput2016-22) Possible environmental factors include [being raised in a city](https://en.wikipedia.org/wiki/Risk_factors_of_schizophrenia#Urbanicity "Risk factors of schizophrenia"), childhood adversity, [cannabis](https://en.wikipedia.org/wiki/Cannabis_\(drug\) "Cannabis (drug)") use during adolescence, infections, the [age of a person's mother](https://en.wikipedia.org/wiki/Advanced_maternal_age "Advanced maternal age") or [father](https://en.wikipedia.org/wiki/Paternal_age_effect "Paternal age effect"), and poor [nutrition during pregnancy](https://en.wikipedia.org/wiki/Prenatal_nutrition "Prenatal nutrition").[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)[\[23\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Parakh2013-23)
About half of those diagnosed with schizophrenia will experience a marked improvement over the long term with no further relapses, and a small proportion of these will recover completely.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[24\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vita2018-24) The other half will have a lifelong impairment.[\[25\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Law2015-25) In severe cases, people may be admitted to hospitals.[\[24\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vita2018-24) Social problems such as [long-term unemployment](https://en.wikipedia.org/wiki/Long-term_unemployment "Long-term unemployment"), poverty, [homelessness](https://en.wikipedia.org/wiki/Homelessness "Homelessness"), exploitation, and victimization are commonly correlated with schizophrenia.[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26)[\[27\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Charleson2018-27) Compared to the general population, people with schizophrenia have a higher suicide rate (about 5% overall) and more [physical health problems](https://en.wikipedia.org/wiki/Physical_health_in_schizophrenia "Physical health in schizophrenia"),[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28)[\[29\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jop2010-29) leading to an average decrease in [life expectancy](https://en.wikipedia.org/wiki/Life_expectancy "Life expectancy") by 20[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13) to 28 years.[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) In 2015, an estimated 17,000 deaths were linked to schizophrenia.[\[16\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2015-16)
The mainstay of treatment is [antipsychotic](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic") medication, including [olanzapine](https://en.wikipedia.org/wiki/Olanzapine "Olanzapine") and [risperidone](https://en.wikipedia.org/wiki/Risperidone "Risperidone"), along with [counseling](https://en.wikipedia.org/wiki/Psychotherapy "Psychotherapy"), job training, and [social rehabilitation](https://en.wikipedia.org/wiki/Psychiatric_rehabilitation "Psychiatric rehabilitation").[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) Up to a third of people do not respond to initial antipsychotics, in which case [clozapine](https://en.wikipedia.org/wiki/Clozapine "Clozapine") is offered.[\[30\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Siskind2017-30) Most antipsychotics improve schizophrenia symptoms, with [clozapine](https://en.wikipedia.org/wiki/Clozapine "Clozapine") the most effective overall; side effects vary considerably and guide treatment choices.[\[31\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:3-31) In situations where doctors judge that there is a risk of harm to self or others, they may impose short [involuntary hospitalization](https://en.wikipedia.org/wiki/Involuntary_commitment "Involuntary commitment").[\[32\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BeckerKilian2006-32) Long-term hospitalization is used on a small number of people with severe schizophrenia.[\[33\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Capdevielle2009-33) In some countries where supportive services are limited or unavailable, long-term hospital stays are more common.[\[34\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Narayan2012-34)
Signs and symptoms
Schizophrenia is a [mental disorder](https://en.wikipedia.org/wiki/Mental_disorder "Mental disorder") characterized by significant alterations in [perception](https://en.wikipedia.org/wiki/Perception "Perception"), thoughts, mood, and behavior.[\[35\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NICE2014-35) Symptoms are described in terms of positive, negative, and cognitive symptoms.[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3)[\[36\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-36) The positive symptoms of schizophrenia are the same for any [psychosis](https://en.wikipedia.org/wiki/Psychosis "Psychosis") and are sometimes referred to as psychotic symptoms. These may be present in any of the different psychoses and are often transient, making early diagnosis of schizophrenia problematic. Psychosis noted for the first time in a person who is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP).[\[37\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-RAISE-37)[\[38\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-38)
Positive symptoms
[](https://en.wikipedia.org/wiki/File:Disorganized_Numbers.jpg)
Example of delusional obsession with numbers, disorganized thoughts, occurring with paranoid schizophrenia.
Positive symptoms are those that are not normally experienced, but are present in people during a psychotic episode in schizophrenia, including [delusions](https://en.wikipedia.org/wiki/Delusion "Delusion"), [hallucinations](https://en.wikipedia.org/wiki/Hallucination "Hallucination"), and disorganized thoughts, speech and behavior or inappropriate affect, typically regarded as manifestations of psychosis.[\[37\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-RAISE-37) Hallucinations occur at some point in the lifetimes of 80% of those with schizophrenia[\[39\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Montagnese2021-39) and most commonly involve the sense of [hearing](https://en.wikipedia.org/wiki/Hearing "Hearing") (most often [hearing voices](https://en.wikipedia.org/wiki/Auditory_verbal_hallucinations "Auditory verbal hallucinations")), but can sometimes involve any of the other [senses](https://en.wikipedia.org/wiki/Sense "Sense") such as [taste](https://en.wikipedia.org/wiki/Taste "Taste"), [sight](https://en.wikipedia.org/wiki/Visual_perception "Visual perception"), [smell](https://en.wikipedia.org/wiki/Olfaction "Olfaction"), and [touch](https://en.wikipedia.org/wiki/Tactile_hallucination "Tactile hallucination").[\[40\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-40) The frequency of hallucinations involving multiple senses is double the rate of those involving only one sense.[\[39\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Montagnese2021-39) They are also typically related to the content of the delusional theme.[\[41\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSMIV-41) [Delusions](https://en.wikipedia.org/wiki/Delusion "Delusion") are [bizarre](https://en.wikipedia.org/wiki/Delusion#Types "Delusion") or [persecutory](https://en.wikipedia.org/wiki/Persecutory_delusions "Persecutory delusions") in nature. [Distortions of self-experience](https://en.wikipedia.org/wiki/Self-disorder "Self-disorder") such as feeling that [others can hear one's thoughts](https://en.wikipedia.org/wiki/Thought_broadcasting "Thought broadcasting") (thought broadcasting delusion) or that [thoughts are being inserted into one's mind](https://en.wikipedia.org/wiki/Thought_insertion "Thought insertion"), sometimes termed passivity phenomena, are also common.[\[42\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Heinz2016-42)[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3) The type and content of auditory and visual hallucinations appears to be influenced, at least in part, by cultural and religious factors. Patients in the United Kingdom and United States are more likely to report hearing criticisms and commands; patients in Africa, Asia, and the Middle East report more religious messaging in their hallucinations. This is true even among transplants to these countries, suggesting these differences are cultural, and not genetic.\[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed "Wikipedia:Citation needed")*\] Positive symptoms generally respond well to medication[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) and become reduced over the course of the illness, perhaps linked to the age-related decline in dopamine activity.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)
Negative symptoms
Negative symptoms are deficits of normal emotional responses, or of other thought processes. The five recognized domains of negative symptoms are: [blunted affect](https://en.wikipedia.org/wiki/Blunted_affect "Blunted affect") – showing flat expressions (monotone) or little emotion; [alogia](https://en.wikipedia.org/wiki/Alogia "Alogia") – a poverty of speech; [anhedonia](https://en.wikipedia.org/wiki/Anhedonia "Anhedonia") – an inability to feel pleasure; [asociality](https://en.wikipedia.org/wiki/Asociality "Asociality") – the lack of desire to form relationships, and [avolition](https://en.wikipedia.org/wiki/Avolition "Avolition") – a lack of motivation and [apathy](https://en.wikipedia.org/wiki/Apathy "Apathy").[\[43\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Adida2015-43)[\[44\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-44) Avolition and anhedonia are seen as motivational deficits resulting from impaired reward processing.[\[45\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-45)[\[46\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Husain2018-46) Reward is the main driver of motivation and this is mostly mediated by dopamine.[\[46\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Husain2018-46) It has been suggested that negative symptoms are multidimensional and they have been categorised into two subdomains of apathy or lack of motivation, and diminished expression.[\[43\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Adida2015-43)[\[47\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Galderisi2018-47) Apathy includes avolition, anhedonia, and social withdrawal; diminished expression includes blunt affect and alogia.[\[48\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-48) Sometimes diminished expression is treated as both verbal and non-verbal.[\[49\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-49)
Apathy accounts for around 50% of the most often found negative symptoms and affects functional outcome and subsequent quality of life. Apathy is related to disrupted cognitive processing affecting memory and planning, including goal-directed behaviour.[\[50\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-50) The two subdomains have suggested a need for separate treatment approaches.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51) A lack of distress is another noted negative symptom.[\[52\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Tatsumi2020-52) A distinction is often made between those negative symptoms that are inherent to schizophrenia, termed primary; and those that result from positive symptoms, from the side effects of antipsychotics, substance use disorder, and social deprivation, termed secondary negative symptoms.[\[53\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-53) Negative symptoms are less responsive to medication and the most difficult to treat.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51) However, if properly assessed, secondary negative symptoms are amenable to treatment.[\[47\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Galderisi2018-47) There is some evidence that the negative symptoms of schizophrenia are amenable to psychostimulant medication, although such drugs have varying degrees of risk for causing positive psychotic symptoms.[\[54\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lindenmayer_Nasrallah_Pucci_systematic_review-54)
Scales for specifically assessing the presence of negative symptoms, and for measuring their severity, and their changes have been introduced since the earlier scales such as the [PANSS](https://en.wikipedia.org/wiki/Positive_and_Negative_Syndrome_Scale "Positive and Negative Syndrome Scale") that deals with all types of symptoms.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51) These scales are the *Clinical Assessment Interview for Negative Symptoms* (CAINS), and the *Brief Negative Symptom Scale* (BNSS) also known as second-generation scales.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51)[\[52\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Tatsumi2020-52)[\[55\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-55) In 2020, ten years after its introduction, a cross-cultural study of the use of BNSS found valid and reliable [psychometric](https://en.wikipedia.org/wiki/Psychometric "Psychometric") evidence for its five-domain structure cross-culturally. The BNSS can assess both the presence and severity of negative symptoms of the five recognized domains and an additional item of reduced normal distress. It has been used to measure changes in negative symptoms in trials of psychosocial and pharmacological interventions.[\[52\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Tatsumi2020-52)
Cognitive symptoms
[](https://en.wikipedia.org/wiki/File:SchizophreniaBrain.jpg)
Map of deficits in [neural tissue](https://en.wikipedia.org/wiki/Neural_tissue "Neural tissue") throughout the human brain in a patient with schizophrenia. The most deficient areas are magenta, while the least deficient areas are blue.
[](https://en.wikipedia.org/wiki/File:Schizophrenia_brain_large.gif)
Diagram of the brain in schizophrenia
An estimated 70% of those with schizophrenia have cognitive deficits, and these are most pronounced in early-onset and late-onset illness.[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56)[\[57\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kar2016-57) These are often evident long before the onset of illness in the [prodromal stage](https://en.wikipedia.org/wiki/Prodromal_schizophrenia "Prodromal schizophrenia"), and may be present in childhood or early adolescence.[\[58\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Bozikas2011-58)[\[59\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-59) They are core features but not considered core symptoms, as are positive and negative symptoms.[\[60\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Biedermann2016-60)[\[61\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vidailhet2013-61) However, their presence and degree of dysfunction are taken as better indicators of functionality than the presentation of core symptoms.[\[58\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Bozikas2011-58) Cognitive deficits become worse at first episode psychosis but then return to baseline, and remain fairly stable over the course of the illness.[\[62\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Hashimoto2019-62)[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63)
Cognitive deficits may be of [neurocognition](https://en.wikipedia.org/wiki/Neurocognition "Neurocognition") (nonsocial) or of [social cognition](https://en.wikipedia.org/wiki/Social_cognition "Social cognition").[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) Neurocognition is the ability to receive and remember information, and includes verbal fluency, [memory](https://en.wikipedia.org/wiki/Memory "Memory"), [reasoning](https://en.wikipedia.org/wiki/Reason "Reason"), [problem solving](https://en.wikipedia.org/wiki/Problem_solving "Problem solving"), [speed of processing](https://en.wikipedia.org/wiki/Information_processing_\(psychology\) "Information processing (psychology)"), and [auditory](https://en.wikipedia.org/wiki/Auditory_system "Auditory system") and visual perception.[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63) [Verbal memory](https://en.wikipedia.org/wiki/Verbal_memory "Verbal memory") and attention are seen to be the most affected.[\[64\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Megreya2016-64)[\[65\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-65) Verbal memory impairment is associated with a decreased level of [semantic processing](https://en.wikipedia.org/wiki/Semantic_processing "Semantic processing") (relating meaning to words).[\[66\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-66) Another memory impairment is that of [episodic memory](https://en.wikipedia.org/wiki/Episodic_memory "Episodic memory").[\[67\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-67) An impairment in visual perception that is consistently found in schizophrenia is that of [visual backward masking](https://en.wikipedia.org/wiki/Visual_backward_masking "Visual backward masking").[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63) [Visual processing](https://en.wikipedia.org/wiki/Visual_processing "Visual processing") impairments include an inability to perceive complex [visual illusions](https://en.wikipedia.org/wiki/Visual_illusion "Visual illusion").[\[68\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-68) Social cognition is concerned with the mental operations needed to interpret, and understand the self and others in the social world.[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63)[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) This is also an associated impairment, and [facial emotion perception](https://en.wikipedia.org/wiki/Face_perception#Schizophrenia "Face perception") is often found to be difficult.[\[69\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-69)[\[70\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-70) Cognitive impairments do not usually respond to antipsychotics, and there are a number of [interventions](https://en.wikipedia.org/wiki/Schizophrenia#Psychosocial_interventions) that are used to try to improve them; [cognitive remediation therapy](https://en.wikipedia.org/wiki/Cognitive_remediation_therapy "Cognitive remediation therapy") is of particular help.[\[61\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vidailhet2013-61)
[Neurological soft signs](https://en.wikipedia.org/wiki/Neurological_soft_signs "Neurological soft signs") of clumsiness and loss of fine motor movement are often found in schizophrenia, which may resolve with effective treatment of FEP.[\[19\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2019-19)[\[71\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-71)
Onset
Onset typically occurs between the late teens and early 30s, with the peak incidence occurring in males in the early to mid-twenties, and in females in the late twenties.[\[3\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIH2022-3)[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[19\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2019-19) Onset before the age of 17 is known as early-onset,[\[72\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-72) and before the age of 13, as can sometimes occur, is known as [childhood schizophrenia](https://en.wikipedia.org/wiki/Childhood_schizophrenia "Childhood schizophrenia") or very early-onset.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[73\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DaFonseca2018-73) Onset can occur between the ages of 40 and 60, known as late-onset schizophrenia.[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) Onset over the age of 60, which may be difficult to differentiate as schizophrenia, is known as very-late-onset schizophrenia-like psychosis.[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) Late onset has shown that a higher rate of females are affected; they have less severe symptoms and need lower doses of antipsychotics.[\[56\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Murante2017-56) The tendency for earlier onset in males is later seen to be balanced by a [post-menopausal](https://en.wikipedia.org/wiki/Post-menopausal "Post-menopausal") increase in the development in females. [Estrogen](https://en.wikipedia.org/wiki/Estrogen "Estrogen") produced pre-menopause has a dampening effect on dopamine receptors but its protection can be overridden by a genetic overload.[\[74\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-74) There has been a dramatic increase in the numbers of older adults with schizophrenia.[\[75\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-75)
Onset may happen suddenly or may occur after the slow and gradual development of a number of signs and symptoms, a period known as the [prodromal stage](https://en.wikipedia.org/wiki/Prodromal_schizophrenia "Prodromal schizophrenia").[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) Up to 75% of those with schizophrenia go through a prodromal stage.[\[76\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-George2017-76) The negative and cognitive symptoms in the prodrome stage can precede FEP (first episode psychosis) by many months and up to five years.[\[62\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Hashimoto2019-62)[\[77\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Conroy2018-77) The period from FEP and treatment is known as the duration of untreated psychosis (DUP) which is seen to be a factor in functional outcome. The prodromal stage is the high-risk stage for the development of psychosis.[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63) Since the progression to first episode psychosis is not inevitable, an alternative term is often preferred of [at risk mental state](https://en.wikipedia.org/wiki/At_risk_mental_state "At risk mental state").[\[63\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Green2019-63) Cognitive dysfunction at an early age impacts a young person's usual cognitive development.[\[78\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-78) Recognition and early intervention at the prodromal stage would minimize the associated disruption to educational and social development and has been the focus of many studies.[\[62\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Hashimoto2019-62)[\[77\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Conroy2018-77)
Risk factors
Schizophrenia is described as a [neurodevelopmental disorder](https://en.wikipedia.org/wiki/Neurodevelopmental_disorder "Neurodevelopmental disorder") with no precise boundary, or single cause, and is thought to develop from [gene–environment interactions](https://en.wikipedia.org/wiki/Gene%E2%80%93environment_interaction "Gene–environment interaction") with involved vulnerability factors.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)[\[79\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-79)[\[80\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Davis2016-80) The interactions of these [risk factors](https://en.wikipedia.org/wiki/Risk_factor_\(epidemiology\) "Risk factor (epidemiology)") are complex, as numerous and diverse [insults](https://en.wikipedia.org/wiki/Insult_\(medical\) "Insult (medical)") from conception to adulthood can be involved.[\[80\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Davis2016-80) A genetic predisposition on its own, without interacting environmental factors, will not give rise to the development of schizophrenia.[\[80\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Davis2016-80)[\[81\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Perkovic2017-81) The genetic component means that [prenatal](https://en.wikipedia.org/wiki/Prenatal_development "Prenatal development") brain development is disturbed, and environmental influence affects the postnatal development of the brain.[\[82\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Suvisaari2010-82) Evidence suggests that genetically susceptible children are more likely to be vulnerable to the effects of environmental risk factors.[\[82\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Suvisaari2010-82)
Genetic
Estimates of the [heritability](https://en.wikipedia.org/wiki/Heritability "Heritability") of schizophrenia are between 70% and 80%, which implies that 70% to 80% of the individual differences in risk of schizophrenia are associated with genetics.[\[22\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-vandeLeemput2016-22)[\[83\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Her2011-83) These estimates vary because of the [difficulty in separating](https://en.wikipedia.org/wiki/Behavioural_genetics "Behavioural genetics") genetic and environmental influences, and their accuracy has been queried.[\[84\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-84)[\[85\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Torrey2019-85) The greatest risk factor for developing schizophrenia is having a [first-degree relative](https://en.wikipedia.org/wiki/First-degree_relative "First-degree relative") with the disease (risk is 6.5%); more than 40% of [identical twins](https://en.wikipedia.org/wiki/Twin#Monozygotic_\(identical\)_twins "Twin") of those with schizophrenia are also affected.[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86) If one parent is affected the risk is about 13% and if both are affected the risk is nearly 50%.[\[83\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Her2011-83) However, the *DSM-5* indicates that most people with schizophrenia have no family history of psychosis.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) Results of [candidate gene](https://en.wikipedia.org/wiki/Candidate_gene "Candidate gene") studies of schizophrenia have generally failed to find consistent associations,[\[87\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-87) and the [genetic loci](https://en.wikipedia.org/wiki/Genetic_loci "Genetic loci") identified by [genome-wide association studies](https://en.wikipedia.org/wiki/Genome-wide_association_studies "Genome-wide association studies") explain only a small fraction of the variation in the disease.[\[88\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-88)
Many [genes](https://en.wikipedia.org/wiki/Genes "Genes") are known to be involved in schizophrenia, each with small effects and unknown [transmission](https://en.wikipedia.org/wiki/Gene#Molecular_inheritance "Gene") and [expression](https://en.wikipedia.org/wiki/Gene_expression "Gene expression").[\[22\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-vandeLeemput2016-22)[\[89\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-89)[\[90\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-90) The summation of these effect sizes into a [polygenic risk score](https://en.wikipedia.org/wiki/Polygenic_score "Polygenic score") can explain at least 7% of the variability in liability for schizophrenia.[\[91\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-91) Around 5% of cases of schizophrenia are understood to be at least partially attributable to rare [copy number variations](https://en.wikipedia.org/wiki/Copy_number_variation "Copy number variation") (CNVs); these [structural variations](https://en.wikipedia.org/wiki/Structural_variation "Structural variation") are associated with known genomic disorders involving [deletions](https://en.wikipedia.org/wiki/Deletion_\(genetics\) "Deletion (genetics)") at [22q11.2](https://en.wikipedia.org/wiki/Chromosome_22#Chromosomal_conditions "Chromosome 22") ([DiGeorge syndrome](https://en.wikipedia.org/wiki/DiGeorge_syndrome "DiGeorge syndrome")) and [17q12](https://en.wikipedia.org/wiki/Chromosome_17#Diseases_and_disorders "Chromosome 17") ([17q12 microdeletion syndrome](https://en.wikipedia.org/wiki/17q12_microdeletion_syndrome "17q12 microdeletion syndrome")), duplications at [16p11.2](https://en.wikipedia.org/wiki/Chromosome_16#Cytogenetic_band "Chromosome 16") (most frequently found) and deletions at [15q11.2](https://en.wikipedia.org/wiki/Chromosome_15#Cytogenetic_band "Chromosome 15") ([Burnside–Butler syndrome](https://en.wikipedia.org/wiki/Burnside%E2%80%93Butler_syndrome "Burnside–Butler syndrome")).[\[92\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lowther2017p82-92) Some of these CNVs increase the risk of developing schizophrenia by as much as 20-fold, and are frequently comorbid with autism and intellectual disabilities.[\[92\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lowther2017p82-92)
The genes [CRHR1](https://en.wikipedia.org/wiki/CRHR1 "CRHR1") and [CRHBP](https://en.wikipedia.org/wiki/CRHBP "CRHBP") are associated with the severity of suicidal behavior. These genes code for stress response proteins needed in the control of the [HPA axis](https://en.wikipedia.org/wiki/HPA_axis "HPA axis"), and their interaction can affect this axis. Response to stress can cause lasting changes in the [function of the HPA axis](https://en.wikipedia.org/wiki/HPA_axis#Stress_and_development "HPA axis") possibly disrupting the negative feedback mechanism, [homeostasis](https://en.wikipedia.org/wiki/Homeostasis "Homeostasis"), and the regulation of emotion leading to altered behaviors.[\[81\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Perkovic2017-81)
The question of how schizophrenia could be primarily genetically influenced, given that people with schizophrenia have lower fertility rates, is a paradox. It is expected that [genetic variants](https://en.wikipedia.org/wiki/Allele "Allele") that increase the risk of schizophrenia would be selected against, due to their negative effects on [reproductive fitness](https://en.wikipedia.org/wiki/Reproductive_fitness "Reproductive fitness"). A number of potential explanations have been proposed, including that [alleles](https://en.wikipedia.org/wiki/Allele "Allele") associated with schizophrenia risk confers a fitness advantage in unaffected individuals.[\[93\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-93)[\[94\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-94) While some evidence has not supported this idea,[\[85\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Torrey2019-85) others propose that a large number of alleles each contributing a small amount can persist.[\[95\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-95)
A meta-analysis found that oxidative [DNA damage](https://en.wikipedia.org/wiki/DNA_damage_\(naturally_occurring\) "DNA damage (naturally occurring)") was significantly increased in schizophrenia.[\[96\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Goh2021-96)
Environmental
Environmental factors, each associated with a slight risk of developing schizophrenia in later life include [oxygen deprivation](https://en.wikipedia.org/wiki/Intrauterine_hypoxia "Intrauterine hypoxia"), infection, [prenatal maternal stress](https://en.wikipedia.org/wiki/Prenatal_maternal_stress "Prenatal maternal stress"), and malnutrition in the mother during prenatal development.[\[97\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Stilo2019-97) A risk is associated with maternal obesity, in increasing [oxidative stress](https://en.wikipedia.org/wiki/Oxidative_stress "Oxidative stress"), and dysregulating the dopamine and serotonin pathways.[\[98\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-98) Both maternal stress and infection have been demonstrated to alter fetal [neurodevelopment](https://en.wikipedia.org/wiki/Neurodevelopment "Neurodevelopment") through an increase of pro-inflammatory [cytokines](https://en.wikipedia.org/wiki/Cytokine "Cytokine").[\[99\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Upthegrove2020-99) There is a slighter risk associated with being born in the winter or spring possibly due to [vitamin D deficiency](https://en.wikipedia.org/wiki/Vitamin_D_deficiency "Vitamin D deficiency")[\[100\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Chiang2016-100) or a prenatal [viral infection](https://en.wikipedia.org/wiki/Viral_infection "Viral infection").[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86) Other infections during pregnancy or around the time of birth that have been linked to an increased risk include infections by *[Toxoplasma gondii](https://en.wikipedia.org/wiki/Toxoplasma_gondii "Toxoplasma gondii")* and *[Chlamydia](https://en.wikipedia.org/wiki/Chlamydia_infection "Chlamydia infection")*.[\[101\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-101) The increased risk is about five to eight percent.[\[102\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-yolken-102) Viral infections of the brain during childhood are also linked to a risk of schizophrenia during adulthood.[\[103\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-103) [Cat exposure](https://en.wikipedia.org/wiki/Human_interaction_with_cats "Human interaction with cats") is also associated with an increased risk of broadly defined schizophrenia-related disorders, with an [odds ratio](https://en.wikipedia.org/wiki/Odds_ratio "Odds ratio") of 2.4.[\[104\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-104) Exposure to specific medications such as [tramadol](https://en.wikipedia.org/wiki/Tramadol "Tramadol") and [desmopressin](https://en.wikipedia.org/wiki/Desmopressin "Desmopressin") has been found be associated with an increased risk of incident schizophrenia, while other medications including [anti-protozoans](https://en.wikipedia.org/wiki/Antiprotozoal "Antiprotozoal") were associated with a decrease in schizophrenia risk.[\[105\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-105)
[Adverse childhood experiences](https://en.wikipedia.org/wiki/Adverse_childhood_experiences "Adverse childhood experiences") (ACEs), severe forms of which are classed as [childhood trauma](https://en.wikipedia.org/wiki/Childhood_trauma "Childhood trauma"), range from being bullied or abused, to the death of a parent.[\[106\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pearce2019-106) Many adverse childhood experiences can cause [toxic stress](https://en.wikipedia.org/wiki/Toxic_stress "Toxic stress") and increase the risk of psychosis.[\[106\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pearce2019-106)[\[107\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-107)[\[108\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-108) Chronic trauma, including ACEs, can promote lasting inflammatory dysregulation throughout the nervous system.[\[109\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Nettis2020-109) It is suggested that early stress may contribute to the development of schizophrenia through these alterations in the immune system.[\[109\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Nettis2020-109) Schizophrenia was the last diagnosis to benefit from the link made between ACEs and adult mental health outcomes.[\[110\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-110)
Living in an [urban environment](https://en.wikipedia.org/wiki/Risk_factors_of_schizophrenia#Urbanicity "Risk factors of schizophrenia") during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two,[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28)[\[111\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-111) even after taking into account [drug use](https://en.wikipedia.org/wiki/Recreational_drug_use "Recreational drug use"), [ethnic group](https://en.wikipedia.org/wiki/Ethnic_group "Ethnic group"), and size of [social group](https://en.wikipedia.org/wiki/Social_group "Social group").[\[112\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-112) A possible link between the [urban environment and pollution](https://en.wikipedia.org/wiki/Neuroplastic_effects_of_pollution "Neuroplastic effects of pollution") has been suggested to be the cause of the elevated risk of schizophrenia.[\[113\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-113) Other risk factors include [social isolation](https://en.wikipedia.org/wiki/Social_isolation "Social isolation"), immigration related to social adversity and racial discrimination, family dysfunction, unemployment, and poor housing conditions.[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)[\[114\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-114)[\[115\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-115) Having a [father older than 40 years](https://en.wikipedia.org/wiki/Paternal_age_effect "Paternal age effect"), or parents younger than 20 years are also associated with schizophrenia.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)[\[116\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-116)
Substance use
About half of those with schizophrenia use [recreational drugs](https://en.wikipedia.org/wiki/Recreational_drugs "Recreational drugs") including [alcohol](https://en.wikipedia.org/wiki/Alcohol_\(drug\) "Alcohol (drug)"), tobacco, and [cannabis](https://en.wikipedia.org/wiki/Cannabis_\(drug\) "Cannabis (drug)") excessively.[\[117\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Gregg2007-117)[\[118\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-118) Use of [stimulants](https://en.wikipedia.org/wiki/Stimulant "Stimulant") such as [amphetamine](https://en.wikipedia.org/wiki/Amphetamine "Amphetamine") and [cocaine](https://en.wikipedia.org/wiki/Cocaine "Cocaine") can lead to a temporary [stimulant psychosis](https://en.wikipedia.org/wiki/Stimulant_psychosis "Stimulant psychosis"), which presents very similarly to schizophrenia.[\[119\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-119) Rarely, alcohol use can also result in a similar [alcohol-related psychosis](https://en.wikipedia.org/wiki/Alcoholic_hallucinosis "Alcoholic hallucinosis").[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)[\[120\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-alcohol-120) Drugs may also be used as coping mechanisms by people who have schizophrenia, to deal with depression, [anxiety](https://en.wikipedia.org/wiki/Anxiety "Anxiety"), boredom, and [loneliness](https://en.wikipedia.org/wiki/Loneliness "Loneliness").[\[117\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Gregg2007-117)[\[121\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Leweke08-121) The use of cannabis and tobacco are not associated with the development of cognitive deficits, and sometimes a reverse relationship is found where their use improves these symptoms.[\[61\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Vidailhet2013-61) However, [substance use disorders](https://en.wikipedia.org/wiki/Substance_use_disorder "Substance use disorder") are associated with an increased risk of suicide, and a poor response to treatment.[\[122\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Khokhar2018-122)[\[123\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-123)
[Cannabis use](https://en.wikipedia.org/wiki/Long-term_effects_of_cannabis#Chronic_psychosis_and_schizophrenia_spectrum_disorders "Long-term effects of cannabis") may be a contributory factor in the development of schizophrenia, potentially increasing the risk of the disease in those who are already at risk.[\[124\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Patel2020-124)[\[125\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Hasan2020-125)[\[126\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-126) The increased risk may require the presence of certain genes within an individual.[\[23\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Parakh2013-23) Its use is associated with doubling the rate.[\[127\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-127)
Causes
The causes of schizophrenia are still unknown. Several models have been put forward to explain the link between altered brain function and schizophrenia.[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28) The prevailing model of schizophrenia is that of a [neurodevelopmental disorder](https://en.wikipedia.org/wiki/Neurodevelopmental_disorder "Neurodevelopmental disorder"), and the underlying changes that occur before symptoms become evident are seen as arising from the [interaction between genes and the environment](https://en.wikipedia.org/wiki/Gene-environment_interaction "Gene-environment interaction").[\[128\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-128) Extensive studies support this model.[\[76\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-George2017-76) Maternal infections, [malnutrition](https://en.wikipedia.org/wiki/Malnutrition "Malnutrition") and [complications during pregnancy](https://en.wikipedia.org/wiki/Complications_of_pregnancy "Complications of pregnancy") and [childbirth](https://en.wikipedia.org/wiki/Obstetric_labor_complication "Obstetric labor complication") are known risk factors for the development of schizophrenia, which usually emerges between the ages of 18 and 25, a period that overlaps with certain stages of neurodevelopment.[\[129\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-129) Gene-environment interactions lead to deficits in the [neural circuitry](https://en.wikipedia.org/wiki/Neural_circuit "Neural circuit") that affect sensory and cognitive functions.[\[76\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-George2017-76)
The common dopamine and glutamate models proposed are not mutually exclusive; each is seen to have a role in the neurobiology of schizophrenia.[\[130\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-130) The most common model put forward was the [dopamine hypothesis of schizophrenia](https://en.wikipedia.org/wiki/Dopamine_hypothesis_of_schizophrenia "Dopamine hypothesis of schizophrenia"), which attributes psychosis to the mind's faulty interpretation of the misfiring of [dopaminergic neurons](https://en.wikipedia.org/wiki/Dopaminergic_pathways "Dopaminergic pathways").[\[131\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-131) This has been directly related to the symptoms of delusions and hallucinations.[\[132\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-132)[\[133\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2014-133)[\[134\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-134) Abnormal dopamine signaling has been implicated in schizophrenia based on the usefulness of medications that affect the dopamine receptor and the observation that dopamine levels are increased during acute psychosis.[\[135\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-135)[\[136\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-136) A decrease in [D1 receptors](https://en.wikipedia.org/wiki/Dopamine_receptor_D1 "Dopamine receptor D1") in the [dorsolateral prefrontal cortex](https://en.wikipedia.org/wiki/Dorsolateral_prefrontal_cortex "Dorsolateral prefrontal cortex") may also be responsible for deficits in [working memory](https://en.wikipedia.org/wiki/Working_memory "Working memory").[\[137\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-137)[\[138\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-138)
The [glutamate hypothesis of schizophrenia](https://en.wikipedia.org/wiki/Glutamate_hypothesis_of_schizophrenia "Glutamate hypothesis of schizophrenia") links alterations between [glutamatergic neurotransmission](https://en.wikipedia.org/wiki/Glutamatergic_neurotransmission "Glutamatergic neurotransmission") and the [neural oscillations](https://en.wikipedia.org/wiki/Neural_oscillation "Neural oscillation") that affect [connections between the thalamus and the cortex](https://en.wikipedia.org/wiki/Thalamocortical_radiations "Thalamocortical radiations").[\[139\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pratt2017-139) Studies have shown that a reduced expression of a [glutamate receptor](https://en.wikipedia.org/wiki/Glutamate_receptor "Glutamate receptor") – [NMDA receptor](https://en.wikipedia.org/wiki/NMDA_receptor "NMDA receptor"), and glutamate blocking drugs such as [phencyclidine](https://en.wikipedia.org/wiki/Phencyclidine "Phencyclidine") and [ketamine](https://en.wikipedia.org/wiki/Ketamine "Ketamine") can mimic the symptoms and cognitive problems associated with schizophrenia.[\[139\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pratt2017-139)[\[140\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-140)[\[141\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-141) Post-mortem studies consistently find that a subset of these neurons fail to express [GAD67](https://en.wikipedia.org/wiki/Glutamate_decarboxylase#Schizophrenia_and_bipolar_disorder "Glutamate decarboxylase") ([GAD1](https://en.wikipedia.org/wiki/GAD1 "GAD1")),[\[142\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marin2012-142) in addition to abnormalities in [brain morphometry](https://en.wikipedia.org/wiki/Brain_morphometry "Brain morphometry"). The subsets of interneurons that are abnormal in schizophrenia are responsible for the synchronizing of neural ensembles needed during working memory tasks. These give the neural oscillations produced as [gamma waves](https://en.wikipedia.org/wiki/Gamma_wave "Gamma wave") that have a frequency of between 30 and 80 [hertz](https://en.wikipedia.org/wiki/Hertz "Hertz"). Both working memory tasks and gamma waves are impaired in schizophrenia, which may reflect abnormal interneuron functionality.[\[142\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marin2012-142)[\[143\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-143)[\[144\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-144)[\[145\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-145) An important process that may be disrupted in neurodevelopment is astrogenesis – the formation of [astrocytes](https://en.wikipedia.org/wiki/Astrocyte "Astrocyte"). Astrocytes are crucial in contributing to the formation and maintenance of neural circuits and it is believed that disruption in this role can result in a number of neurodevelopmental disorders including schizophrenia.[\[146\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Sloan2014-146) Evidence suggests that reduced numbers of astrocytes in deeper cortical layers are assocociated with a diminished expression of [EAAT2](https://en.wikipedia.org/wiki/EAAT2 "EAAT2"), a [glutamate transporter](https://en.wikipedia.org/wiki/Glutamate_transporter "Glutamate transporter") in astrocytes; supporting the glutamate hypothesis.[\[146\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Sloan2014-146)
Deficits in [executive functions](https://en.wikipedia.org/wiki/Executive_function "Executive function"), such as [planning](https://en.wikipedia.org/wiki/Planning "Planning"), [inhibition](https://en.wikipedia.org/wiki/Social_inhibition "Social inhibition"), and [working memory](https://en.wikipedia.org/wiki/Working_memory "Working memory"), are pervasive in schizophrenia. Although these functions are separable, their dysfunction in schizophrenia may reflect an underlying deficit in the ability to represent goal related information in working memory, and to use this to direct cognition and behavior.[\[147\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-147)[\[148\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-148) These impairments have been linked to a number of [neuroimaging](https://en.wikipedia.org/wiki/Neuroimaging "Neuroimaging") and [neuropathological abnormalities](https://en.wikipedia.org/w/index.php?title=Neuropathological_abnormalities&action=edit&redlink=1 "Neuropathological abnormalities (page does not exist)"). For example, functional neuroimaging studies report evidence of reduced neural processing efficiency, whereby the [dorsolateral prefrontal cortex](https://en.wikipedia.org/wiki/Dorsolateral_prefrontal_cortex "Dorsolateral prefrontal cortex") is activated to a greater degree to achieve a certain level of performance relative to controls on working memory tasks. These abnormalities may be linked to the consistent post-mortem finding of reduced [neuropil](https://en.wikipedia.org/wiki/Neuropil "Neuropil"), evidenced by increased [pyramidal cell](https://en.wikipedia.org/wiki/Pyramidal_cell "Pyramidal cell") density and reduced [dendritic spine](https://en.wikipedia.org/wiki/Dendritic_spine "Dendritic spine") density. These cellular and functional abnormalities may also be reflected in structural neuroimaging studies that find reduced [grey matter](https://en.wikipedia.org/wiki/Grey_matter "Grey matter") volume in association with deficits in working memory tasks.[\[149\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-149)
Positive symptoms have been linked to cortical thinning in the [superior temporal gyrus](https://en.wikipedia.org/wiki/Superior_temporal_gyrus "Superior temporal gyrus").[\[150\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-150) The severity of negative symptoms has been linked to reduced thickness in the left medial [orbitofrontal cortex](https://en.wikipedia.org/wiki/Orbitofrontal_cortex "Orbitofrontal cortex").[\[151\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-151) Anhedonia, traditionally defined as a reduced capacity to experience [pleasure](https://en.wikipedia.org/wiki/Pleasure "Pleasure"), is frequently reported in schizophrenia. However, a large body of evidence suggests that [hedonic responses](https://en.wikipedia.org/wiki/Hedonism "Hedonism") are intact in schizophrenia,[\[152\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-152) and that what is reported to be [anhedonia](https://en.wikipedia.org/wiki/Anhedonia "Anhedonia") is a reflection of dysfunction in other processes related to reward.[\[153\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-153) Overall, a failure of reward prediction is thought to lead to impairment in the generation of cognition and behavior required to obtain rewards, despite normal hedonic responses.[\[154\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-154)
Another theory links abnormal [brain lateralization](https://en.wikipedia.org/wiki/Lateralization_of_brain_function "Lateralization of brain function") to the development of [being left-handed](https://en.wikipedia.org/wiki/Handedness "Handedness") which is significantly more common in those with schizophrenia.[\[155\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Wilberg2019-155) This abnormal development of hemispheric asymmetry is noted in schizophrenia.[\[156\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-156) Studies have concluded that the link is a true and verifiable effect that may reflect a genetic link between lateralization and schizophrenia.[\[155\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Wilberg2019-155)[\[157\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-157)
[Bayesian models of brain functioning](https://en.wikipedia.org/wiki/Bayesian_approaches_to_brain_function "Bayesian approaches to brain function") have been used to link abnormalities in cellular functioning to symptoms.[\[158\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-158)[\[159\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-159) Both hallucinations and delusions have been suggested to reflect improper encoding of [prior expectations](https://en.wikipedia.org/wiki/Prior_probability "Prior probability"), thereby causing expectation to excessively influence sensory perception and the formation of beliefs. In approved models of [circuits](https://en.wikipedia.org/wiki/Neural_circuits "Neural circuits") that mediate [predictive coding](https://en.wikipedia.org/wiki/Predictive_coding "Predictive coding"), reduced NMDA receptor activation, could in theory result in the positive symptoms of delusions and hallucinations.[\[160\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-160)[\[161\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-161)[\[162\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-162)
From an [evolutionary](https://en.wikipedia.org/wiki/Evolutionary_psychiatry "Evolutionary psychiatry") [perspective](https://en.wikipedia.org/wiki/Evolutionary_psychology "Evolutionary psychology"), schizophrenia is regarded as an "evolutionary puzzle" because it shows high heritability (~60-80 %) and significant impairment in reproduction, yet persists at ~1 % prevalence. One hypothesis suggests that mild schizotypal traits may have historically conferred advantages (such as enhanced creativity or verbal ability,) while more severe forms represent the breakdown of these systems. Experimental models also propose that selection for language and social-cognitive complexity may have increased vulnerability to psychosis when environmental or developmental stressors intervene.[\[163\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-163)[\[164\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-164)
Diagnosis
Criteria
Schizophrenia is diagnosed based on criteria in either the *[Diagnostic and Statistical Manual of Mental Disorders](https://en.wikipedia.org/wiki/Diagnostic_and_Statistical_Manual_of_Mental_Disorders "Diagnostic and Statistical Manual of Mental Disorders")* (DSM) published by the [American Psychiatric Association](https://en.wikipedia.org/wiki/American_Psychiatric_Association "American Psychiatric Association") or the [International Statistical Classification of Diseases and Related Health Problems](https://en.wikipedia.org/wiki/ICD "ICD") (ICD) published by the [World Health Organization](https://en.wikipedia.org/wiki/World_Health_Organization "World Health Organization") (WHO). These criteria use the self-reported experiences of the person and reported abnormalities in behavior, followed by a [psychiatric assessment](https://en.wikipedia.org/wiki/Psychiatric_assessment "Psychiatric assessment"). The [mental status examination](https://en.wikipedia.org/wiki/Mental_status_examination "Mental status examination") is an important part of the assessment.[\[165\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-165) An established tool for assessing the severity of positive and negative symptoms is the [Positive and Negative Syndrome Scale](https://en.wikipedia.org/wiki/Positive_and_Negative_Syndrome_Scale "Positive and Negative Syndrome Scale") (PANSS).[\[166\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-166) This has been seen to have shortcomings relating to negative symptoms, and other scales – the *Clinical Assessment Interview for Negative Symptoms* (CAINS), and the *Brief Negative Symptoms Scale* (BNSS) have been introduced.[\[51\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Marder2014-51) The [DSM-5](https://en.wikipedia.org/wiki/DSM-5 "DSM-5"), published in 2013, gives a *Scale to Assess the Severity of Symptom Dimensions* outlining eight dimensions of symptoms.[\[60\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Biedermann2016-60)
DSM-5 states that to be diagnosed with schizophrenia, two diagnostic criteria have to be met over the period of one month, with a significant impact on social or occupational functioning for at least six months. One of the symptoms needs to be either delusions, hallucinations, or disorganized speech. A second symptom could be one of the negative symptoms, or severely disorganized or [catatonic behaviour](https://en.wikipedia.org/wiki/Catatonia "Catatonia").[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) A different diagnosis of [schizophreniform disorder](https://en.wikipedia.org/wiki/Schizophreniform_disorder "Schizophreniform disorder") can be made before the six months needed for the diagnosis of schizophrenia.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)
In Australia, the guideline for diagnosis is for six months or more with symptoms severe enough to affect ordinary functioning.[\[167\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-167) In the UK diagnosis is based on having the symptoms for most of the time for one month, with symptoms that significantly affect the ability to work, study, or carry on ordinary daily living, and with other similar conditions ruled out.[\[168\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-168)
The ICD criteria are typically used in European countries; the DSM criteria are used predominantly in the United States and Canada, and are prevailing in research studies. In practice, agreement between the two systems is high.[\[169\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-169) The current proposal for the [ICD-11](https://en.wikipedia.org/wiki/ICD-11 "ICD-11") criteria for schizophrenia recommends adding self-disorder as a symptom.[\[42\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Heinz2016-42)
A major unresolved difference between the two diagnostic systems is that of the requirement in DSM of an impaired functional outcome. WHO for ICD argues that not all people with schizophrenia have functional deficits and so these are not specific for the diagnosis.[\[60\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Biedermann2016-60)
Neuroimaging techniques
[Functional magnetic resonance imaging (fMRI)](https://en.wikipedia.org/wiki/Functional_MRI_methods_and_findings_in_schizophrenia "Functional MRI methods and findings in schizophrenia") has become a tool in understanding brain activity and connectivity differences in individuals with schizophrenia. Through resting-state fMRI, researchers have observed altered connectivity patterns within several key brain networks, such as the default mode network (DMN),[\[170\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-170) salience network (SN),[\[171\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-171) and central executive network (CEN).[\[172\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-172) Alterations may underlie cognitive and emotional symptoms in schizophrenia, such as disorganized thinking, impaired attention, and emotional dysregulation.
Comorbidities
[](https://en.wikipedia.org/wiki/File:Overlapping_clinical_phenotypes_in_genes_associated_with_monogenic_forms_of_autism_spectrum_disorder_\(ASD\),_dystonia,_epilepsy_and_schizophrenia.svg)
[Euler diagram](https://en.wikipedia.org/wiki/Euler_diagram "Euler diagram") showing overlapping [clinical phenotypes](https://en.wikipedia.org/wiki/Clinical_phenotype "Clinical phenotype") in genes associated with [monogenic forms](https://en.wikipedia.org/wiki/Monogenic_disease "Monogenic disease") of [autism spectrum disorder](https://en.wikipedia.org/wiki/Autism_spectrum_disorder "Autism spectrum disorder") (ASD), [dystonia](https://en.wikipedia.org/wiki/Dystonia "Dystonia"), [epilepsy](https://en.wikipedia.org/wiki/Epilepsy "Epilepsy") and schizophrenia:
Genes associated with epilepsy
Genes associated with schizophrenia
Genes associated with autism spectrum disorder
Genes associated with dystonia
Many people with schizophrenia may have one or more [other mental disorders](https://en.wikipedia.org/wiki/Comorbidity "Comorbidity"), such as [anxiety disorders](https://en.wikipedia.org/wiki/Anxiety_disorders "Anxiety disorders"), [obsessive–compulsive disorder](https://en.wikipedia.org/wiki/Obsessive%E2%80%93compulsive_disorder "Obsessive–compulsive disorder"), or substance use disorder. These are separate disorders that require treatment.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) When comorbid with schizophrenia, substance use disorder and [antisocial personality disorder](https://en.wikipedia.org/wiki/Antisocial_personality_disorder "Antisocial personality disorder") both increase the risk for violence.[\[173\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Richard-Devantoy2009-173) Comorbid substance use disorder also increases the risk of suicide.[\[122\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Khokhar2018-122)
[Sleep disorders](https://en.wikipedia.org/wiki/Sleep_disorder "Sleep disorder") often co-occur with schizophrenia, and may be an early sign of relapse.[\[174\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Staedt2010-174) Sleep disorders are linked with positive symptoms such as [disorganized thinking](https://en.wikipedia.org/wiki/Disorganized_thinking "Disorganized thinking") and can adversely affect [cortical plasticity](https://en.wikipedia.org/wiki/Neuroplasticity "Neuroplasticity") and cognition.[\[174\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Staedt2010-174) The consolidation of memories is disrupted in sleep disorders.[\[175\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pocivavsek2018-175) They are associated with severity of illness, a poor prognosis, and poor quality of life.[\[176\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Monti2013-176)[\[177\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-177) Sleep onset and maintenance insomnia is a common symptom, regardless of whether treatment has been received or not.[\[176\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Monti2013-176) Genetic variations have been found associated with these conditions involving the [circadian rhythm](https://en.wikipedia.org/wiki/Circadian_rhythm "Circadian rhythm"), dopamine and [histamine metabolism](https://en.wikipedia.org/wiki/Histamine#Synthesis_and_metabolism "Histamine"), and signal transduction.[\[178\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-178)
Schizophrenia is also associated with a number of somatic comorbidities including [diabetes mellitus type 2](https://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 "Diabetes mellitus type 2"), [autoimmune diseases](https://en.wikipedia.org/wiki/Autoimmune_disease "Autoimmune disease"), and [cardiovascular diseases](https://en.wikipedia.org/wiki/Cardiovascular_disease "Cardiovascular disease"). The association of these with schizophrenia may be partially due to medications (e.g. [dyslipidemia](https://en.wikipedia.org/wiki/Dyslipidemia "Dyslipidemia") from antipsychotics), environmental factors (e.g. complications from an increased rate of cigarette smoking), or associated with the disorder itself (e.g. diabetes mellitus type 2 and some cardiovascular diseases are thought to be genetically linked). These somatic comorbidities contribute to reduced life expectancy among persons with the disorder.[\[179\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-179)
Differential diagnosis
To make a diagnosis of schizophrenia [other possible causes of psychosis need to be excluded](https://en.wikipedia.org/wiki/Diagnosis_of_exclusion "Diagnosis of exclusion").[\[180\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-180): 858 Psychotic symptoms lasting less than a month may be diagnosed as [brief psychotic disorder](https://en.wikipedia.org/wiki/Brief_psychotic_disorder "Brief psychotic disorder"), or as schizophreniform disorder. Psychosis is noted in *Other specified schizophrenia spectrum and other psychotic disorders* as a DSM-5 category. [Schizoaffective disorder](https://en.wikipedia.org/wiki/Schizoaffective_disorder "Schizoaffective disorder") is diagnosed if symptoms of [mood disorder](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder") are substantially present alongside psychotic symptoms. Psychosis that results from a general medical condition or substance is termed secondary psychosis.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)
Psychotic symptoms may be present in several other conditions, including [bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder"),[\[11\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2010-11) [borderline personality disorder](https://en.wikipedia.org/wiki/Borderline_personality_disorder "Borderline personality disorder"),[\[12\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Paris2018-12) [substance intoxication](https://en.wikipedia.org/wiki/Substance_intoxication "Substance intoxication"), [substance-induced psychosis](https://en.wikipedia.org/wiki/Substance-induced_psychosis "Substance-induced psychosis"), and a number of [drug withdrawal syndromes](https://en.wikipedia.org/wiki/Drug_withdrawal_syndrome "Drug withdrawal syndrome"). Non-bizarre delusions are also present in [delusional disorder](https://en.wikipedia.org/wiki/Delusional_disorder "Delusional disorder"), and social withdrawal in [social anxiety disorder](https://en.wikipedia.org/wiki/Social_anxiety_disorder "Social anxiety disorder"), [avoidant personality disorder](https://en.wikipedia.org/wiki/Avoidant_personality_disorder "Avoidant personality disorder") and [schizotypal personality disorder](https://en.wikipedia.org/wiki/Schizotypal_personality_disorder "Schizotypal personality disorder"). Schizotypal personality disorder has symptoms that are similar but less severe than those of schizophrenia.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) Schizophrenia occurs along with obsessive–compulsive disorder (OCD) considerably more often than could be explained by chance, although it can be difficult to distinguish obsessions that occur in OCD from the delusions of schizophrenia.[\[181\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-181) There can be considerable overlap with the symptoms of [post-traumatic stress disorder](https://en.wikipedia.org/wiki/Post-traumatic_stress_disorder "Post-traumatic stress disorder").[\[182\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-182)
A more general medical and neurological examination may be needed to rule out medical illnesses which may rarely produce psychotic schizophrenia-like symptoms, such as [metabolic disturbance](https://en.wikipedia.org/wiki/Metabolic_disorder "Metabolic disorder"), [systemic infection](https://en.wikipedia.org/wiki/Systemic_infection "Systemic infection"), [syphilis](https://en.wikipedia.org/wiki/Syphilis "Syphilis"), [HIV-associated neurocognitive disorder](https://en.wikipedia.org/wiki/HIV-associated_neurocognitive_disorder "HIV-associated neurocognitive disorder"), [epilepsy](https://en.wikipedia.org/wiki/Epilepsy "Epilepsy"), [limbic encephalitis](https://en.wikipedia.org/wiki/Limbic_encephalitis "Limbic encephalitis"), and brain lesions. Stroke, [multiple sclerosis](https://en.wikipedia.org/wiki/Multiple_sclerosis "Multiple sclerosis"), [hyperthyroidism](https://en.wikipedia.org/wiki/Hyperthyroidism "Hyperthyroidism"), [hypothyroidism](https://en.wikipedia.org/wiki/Hypothyroidism "Hypothyroidism"), and [dementias](https://en.wikipedia.org/wiki/Dementia "Dementia") such as [Alzheimer's disease](https://en.wikipedia.org/wiki/Alzheimer%27s_disease "Alzheimer's disease"), [Huntington's disease](https://en.wikipedia.org/wiki/Huntington%27s_disease "Huntington's disease"), [frontotemporal dementia](https://en.wikipedia.org/wiki/Frontotemporal_dementia "Frontotemporal dementia"), and the [Lewy body dementias](https://en.wikipedia.org/wiki/Lewy_body_dementia "Lewy body dementia") may also be associated with schizophrenia-like psychotic symptoms.[\[183\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-183) It may be necessary to rule out a [delirium](https://en.wikipedia.org/wiki/Delirium "Delirium"), which can be distinguished by visual hallucinations, acute onset and fluctuating [level of consciousness](https://en.wikipedia.org/wiki/Level_of_consciousness "Level of consciousness"), and indicates an underlying medical illness. Investigations are not generally repeated for relapse unless there is a specific *medical* indication or possible [adverse effects](https://en.wikipedia.org/wiki/Adverse_effects "Adverse effects") from [antipsychotic medication](https://en.wikipedia.org/wiki/Antipsychotic_medication "Antipsychotic medication").[\[184\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-184) In children hallucinations must be separated from typical childhood fantasies.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) It is difficult to distinguish childhood schizophrenia from autism.[\[73\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DaFonseca2018-73)
Prevention
[Prevention](https://en.wikipedia.org/wiki/Preventive_healthcare "Preventive healthcare") of schizophrenia is difficult as there are no reliable markers for the later development of the disorder.[\[185\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-185)
[Early intervention programs](https://en.wikipedia.org/wiki/Early_intervention_in_psychosis "Early intervention in psychosis") diagnose and treat patients in the prodromal phase of the illness. There is some evidence that these programs reduce symptoms. Patients tend to prefer early treatment programs to ordinary treatment and are less likely to disengage from them. As of 2020, it is unclear whether the benefits of early treatment persist once the treatment is terminated.[\[186\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-186)
[Cognitive behavioral therapy](https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy "Cognitive behavioral therapy") may reduce the risk of psychosis in those at high risk after a year[\[187\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-187) and is recommended in this group, by the [National Institute for Health and Care Excellence](https://en.wikipedia.org/wiki/National_Institute_for_Health_and_Care_Excellence "National Institute for Health and Care Excellence") (NICE).[\[35\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NICE2014-35) Another preventive measure is to avoid drugs that have been associated with development of the disorder, including [cannabis](https://en.wikipedia.org/wiki/Cannabis_\(drug\) "Cannabis (drug)"), cocaine, and [amphetamines](https://en.wikipedia.org/wiki/Amphetamines "Amphetamines").[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)
Antipsychotics are prescribed following a first-episode psychosis, and following remission, a preventive maintenance use is continued to avoid relapse. However, it is recognized that some people do recover following a single episode and that long-term use of antipsychotics will not be needed but there is no way of identifying this group.[\[188\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Taylor2019-188)
Management
The primary treatment of schizophrenia is the use of [antipsychotic medications](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic"), often in combination with [psychosocial interventions](https://en.wikipedia.org/wiki/Psychosocial_interventions "Psychosocial interventions") and [social supports](https://en.wikipedia.org/wiki/Social_support "Social support").[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28)[\[189\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-189) Community support services including drop-in centers, visits by members of a [community mental health team](https://en.wikipedia.org/wiki/Community_mental_health_service "Community mental health service"), [supported employment](https://en.wikipedia.org/wiki/Supported_employment "Supported employment"),[\[190\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-190) and support groups are common. The time between the onset of psychotic symptoms to being given treatment – the duration of untreated psychosis (DUP) – is associated with a poorer outcome in both the short term and the long term.[\[191\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-191)
[Voluntary](https://en.wikipedia.org/wiki/Voluntary_commitment "Voluntary commitment") or [involuntary](https://en.wikipedia.org/wiki/Involuntary_commitment "Involuntary commitment") admission to hospital may be imposed by doctors and courts who deem a person to be having a severe episode. In the UK, large mental hospitals termed asylums began to be closed down in the 1950s with the advent of antipsychotics, and with an awareness of the negative impact of long-term hospital stays on recovery.[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26) This process was known as [deinstitutionalization](https://en.wikipedia.org/wiki/Deinstitutionalization "Deinstitutionalization"), and community and supportive services were developed to support this change. Many other countries followed suit with the US starting in the 60s.[\[192\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-192) There still remain a smaller group of people who do not improve enough to be discharged.[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26)[\[33\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Capdevielle2009-33) In some countries that lack the necessary supportive and social services, long-term hospital stays are more usual.[\[34\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Narayan2012-34)
Medication
[](https://en.wikipedia.org/wiki/File:Risperdal_tablets.jpg)
[Risperidone](https://en.wikipedia.org/wiki/Risperidone "Risperidone") (trade name Risperdal) is a common [atypical antipsychotic](https://en.wikipedia.org/wiki/Atypical_antipsychotic "Atypical antipsychotic") medication.
Most antipsychotics reduce overall, positive, negative, and depressive symptoms in schizophrenia, with clozapine showing the largest overall effect, though efficacy differences between drugs are mostly gradual.[\[31\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:3-31) Side-effect profiles, including weight gain, sedation, prolactin elevation, and QTc prolongation, vary more distinctly; clinicians weigh benefits against risks based on patient factors and preferences.[\[31\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:3-31)
The first-line treatment for schizophrenia is an antipsychotic. The first-generation antipsychotics, now called [typical antipsychotics](https://en.wikipedia.org/wiki/Typical_antipsychotics "Typical antipsychotics"), like [haloperidol](https://en.wikipedia.org/wiki/Haloperidol "Haloperidol"), are [dopamine antagonists](https://en.wikipedia.org/wiki/Dopamine_antagonist "Dopamine antagonist") that block D2 receptors, and affect the [neurotransmission](https://en.wikipedia.org/wiki/Neurotransmitter "Neurotransmitter") of [dopamine](https://en.wikipedia.org/wiki/Dopamine "Dopamine"). Those brought out later, the second-generation antipsychotics known as [atypical antipsychotics](https://en.wikipedia.org/wiki/Atypical_antipsychotics "Atypical antipsychotics"), including [olanzapine](https://en.wikipedia.org/wiki/Olanzapine "Olanzapine") and [risperidone](https://en.wikipedia.org/wiki/Risperidone "Risperidone"), can also have an effect on another neurotransmitter, [serotonin](https://en.wikipedia.org/wiki/Serotonin "Serotonin"). Antipsychotics can reduce the symptoms of anxiety within hours of their use, but, for other symptoms, they may take several days or weeks to reach their full effect.[\[37\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-RAISE-37)[\[193\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-nhsTreatment-193) They have little effect on negative and cognitive symptoms, which may be helped by additional psychotherapies and medications.[\[194\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-194) There is no single antipsychotic suitable for first-line treatment for everyone, as responses and tolerances vary between people.[\[195\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-195) Stopping medication may be considered after a single psychotic episode where there has been a full recovery with no symptoms for twelve months. Repeated relapses worsen the long-term outlook and the risk of relapse following a second episode is high, and long-term treatment is usually recommended.[\[196\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-196)[\[197\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Harrow2013-197)
About half of those with schizophrenia will respond favourably to antipsychotics, and have a good return of functioning.[\[198\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-198) However, positive symptoms persist in up to a third of people. Following two trials of different antipsychotics over six weeks, that also prove ineffective, they will be classed as having treatment-resistant schizophrenia (TRS), and [clozapine](https://en.wikipedia.org/wiki/Clozapine "Clozapine") will be offered.[\[199\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-199)[\[30\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Siskind2017-30) Clozapine is of benefit to around half of this group although it has the potentially serious side effect of [agranulocytosis](https://en.wikipedia.org/wiki/Agranulocytosis "Agranulocytosis") (lowered [white blood cell](https://en.wikipedia.org/wiki/White_blood_cell "White blood cell") count) in less than 4% of people.[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28)[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)[\[200\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-200)
About 30 to 50 percent of people with schizophrenia do not accept that they have an illness or comply with their recommended treatment.[\[201\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-201) For those who are unwilling or unable to take medication regularly, [long-acting injections](https://en.wikipedia.org/wiki/Injection_\(medicine\)#Depot "Injection (medicine)") of antipsychotics may be used,[\[202\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-202) which reduce the risk of relapse to a greater degree than oral medications.[\[203\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-203) When used in combination with psychosocial interventions, they may improve long-term [adherence](https://en.wikipedia.org/wiki/Adherence_\(medicine\) "Adherence (medicine)") to treatment.[\[204\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Depo06-204)
A 2025 meta-analysis showed xanomeline and trospium's effect in the improvement of symptoms of schizophrenia.[\[205\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-205) The [fixed-dose combination](https://en.wikipedia.org/wiki/Fixed-dose_combination "Fixed-dose combination") medication [xanomeline/trospium chloride](https://en.wikipedia.org/wiki/Xanomeline/trospium_chloride "Xanomeline/trospium chloride") (Cobenfy) was approved for medical use in the United States in September 2024.[\[206\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-FDA_PR_20240926-206)[\[207\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-207) It is the first [cholinergic agonist](https://en.wikipedia.org/wiki/Cholinergic_agonist "Cholinergic agonist") approved by the US [Food and Drug Administration](https://en.wikipedia.org/wiki/Food_and_Drug_Administration "Food and Drug Administration") (FDA) to treat schizophrenia.[\[206\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-FDA_PR_20240926-206)
Negative and cognitive symptoms are an unmet clinical need in antipsychotic-based treatment approaches. Psychostimulant drugs have been found effective in the treatment of negative symptoms, but are rarely prescribed due to concerns about the excacerbation of positive symptoms.[\[54\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lindenmayer_Nasrallah_Pucci_systematic_review-54) It is possible that low-dose psychedelic therapies could be of benefit in schizophrenia through their prosocial and procognitive effects, although there is a serious risk that high dose psychedelic therapies could lead to worsening of positive symptoms.[\[208\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-208)
Adverse effects
[Extrapyramidal symptoms](https://en.wikipedia.org/wiki/Extrapyramidal_symptoms "Extrapyramidal symptoms"), including [akathisia](https://en.wikipedia.org/wiki/Akathisia#Drug-induced "Akathisia"), are associated with all commercially available [antipsychotic](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic") to varying degrees.[\[209\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Chow2020-209): 566 There is little evidence that second generation antipsychotics have reduced levels of extrapyramidical symptoms compared to typical antipsychotics.[\[209\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Chow2020-209): 566 [Tardive dyskinesia](https://en.wikipedia.org/wiki/Tardive_dyskinesia "Tardive dyskinesia") can occur due to long-term use of antipsychotics, developing after months or years of use.[\[210\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-210) The antipsychotic [clozapine](https://en.wikipedia.org/wiki/Clozapine "Clozapine") is also associated with [thromboembolism](https://en.wikipedia.org/wiki/Thromboembolism "Thromboembolism") (including [pulmonary embolism](https://en.wikipedia.org/wiki/Pulmonary_embolism "Pulmonary embolism")), [myocarditis](https://en.wikipedia.org/wiki/Myocarditis "Myocarditis"), and [cardiomyopathy](https://en.wikipedia.org/wiki/Cardiomyopathy "Cardiomyopathy").
A number of psychosocial interventions that include several types of [psychotherapy](https://en.wikipedia.org/wiki/Psychotherapy "Psychotherapy") may be useful in the treatment of schizophrenia such as: [family therapy](https://en.wikipedia.org/wiki/Family_therapy "Family therapy"),[\[211\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pharoah2010-211) [group therapy](https://en.wikipedia.org/wiki/Group_therapy "Group therapy"), cognitive remediation therapy (CRT),[\[212\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-212) cognitive behavioral therapy (CBT),[\[213\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-213) and [metacognitive training](https://en.wikipedia.org/wiki/Metacognitive_training "Metacognitive training").[\[214\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-214)[\[215\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-215) Skills training, help with substance use, and weight management – often needed as a side effect of an antipsychotic – are also offered.[\[216\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-216) In the US, interventions for first episode psychosis have been brought together in an overall approach known as [coordinated speciality care](https://en.wikipedia.org/wiki/Coordinated_speciality_care "Coordinated speciality care") (CSC) and also includes support for education.[\[37\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-RAISE-37) In the UK *care across all phases* is a similar approach that covers many of the treatment guidelines recommended.[\[35\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NICE2014-35) The aim is to reduce the number of relapses and stays in the hospital.[\[211\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pharoah2010-211)
Other support services for education, employment, and housing are usually offered. For people with severe schizophrenia, who are discharged from a stay in the hospital, these services are often brought together in an integrated approach to offer support in the community away from the hospital setting. In addition to medicine management, housing, and finances, assistance is given for more routine matters such as help with shopping and using public transport. This approach is known as [assertive community treatment](https://en.wikipedia.org/wiki/Assertive_community_treatment "Assertive community treatment") (ACT) and has been shown to achieve positive results in symptoms, social functioning and quality of life.[\[217\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-217)[\[218\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-218) Another more intense approach is known as *intensive care management* (ICM). ICM is a stage further than ACT and emphasises support of high intensity in smaller caseloads, (less than twenty). This approach is to provide long-term care in the community. Studies show that ICM improves many of the relevant outcomes including social functioning.[\[219\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-219)
Some studies have shown little evidence for the effectiveness of CBT in either reducing symptoms or preventing relapse.[\[220\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-220)[\[221\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jones2018-221) However, other studies have found that CBT does improve overall psychotic symptoms (when in use with medication) and it has been recommended in Canada, but has been seen to have no effect on social function, relapse, or quality of life.[\[222\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-222) In the UK it is recommended as an add-on therapy in the treatment of schizophrenia.[\[193\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-nhsTreatment-193)[\[221\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jones2018-221) [Arts therapies](https://en.wikipedia.org/wiki/Expressive_therapies "Expressive therapies") are seen to improve negative symptoms in some people, and are recommended by NICE in the UK.[\[193\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-nhsTreatment-193) This approach is criticised as having not been well-researched,[\[223\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-223)[\[224\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-224) and arts therapies are not recommended in Australian guidelines for example.[\[225\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-225) [Peer support](https://en.wikipedia.org/wiki/Peer_support#In_mental_health "Peer support"), in which people with [personal experience](https://en.wikipedia.org/wiki/Experiential_knowledge "Experiential knowledge") of schizophrenia, provide help to each other, is of unclear benefit.[\[226\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-226)
Other
Exercise including aerobic exercise has been shown to improve positive and negative symptoms, cognition, working memory, and improve quality of life.[\[227\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Girdler2019-227)[\[228\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2017-228) Exercise has also been shown to increase the volume of the [hippocampus](https://en.wikipedia.org/wiki/Hippocampus "Hippocampus") in those with schizophrenia. A decrease in hippocampal volume is one of the factors linked to the development of the disease.[\[227\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Girdler2019-227) However, there still remains the problem of increasing motivation for, and maintaining participation in physical activity.[\[229\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-229) Supervised sessions are recommended.[\[228\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2017-228) In the UK healthy eating advice is offered alongside exercise programs.[\[230\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-230)
An inadequate diet is often found in schizophrenia, and associated vitamin deficiencies including those of [folate](https://en.wikipedia.org/wiki/Folate "Folate"), and [vitamin D](https://en.wikipedia.org/wiki/Vitamin_D_deficiency#In_schizophrenia "Vitamin D deficiency") are linked to the risk factors for the development of schizophrenia and for early death including heart disease.[\[231\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2018-231)[\[232\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rastogi2020-232) Those with schizophrenia possibly have the worst diet of all the mental disorders. Lower levels of folate and vitamin D have been noted as significantly lower in first episode psychosis.[\[231\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2018-231) The use of supplemental folate is recommended.[\[233\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-233) A [zinc deficiency](https://en.wikipedia.org/wiki/Zinc_deficiency "Zinc deficiency") has also been noted.[\[234\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2019-234) [Vitamin B12](https://en.wikipedia.org/wiki/Vitamin_B12 "Vitamin B12") is also often deficient and this is linked to worse symptoms. Supplementation with B vitamins has been shown to significantly improve symptoms, and to put in reverse some of the cognitive deficits.[\[231\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2018-231) It is also suggested that the noted dysfunction in gut microbiota might benefit from the use of [probiotics](https://en.wikipedia.org/wiki/Probiotics "Probiotics").[\[234\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Firth2019-234)
Prognosis
[](https://en.wikipedia.org/wiki/File:Schizophrenia_world_map_-_DALY_-_WHO2004.svg)
[Disability-adjusted life years](https://en.wikipedia.org/wiki/Disability-adjusted_life_year "Disability-adjusted life year") lost due to schizophrenia per 100,000 inhabitants in 2004
| | |
|---|---|
| no data ≤ 185 185–197 197–207 207–218 218–229 229–240 | 240–251 251–262 262–273 273–284 284–295 ≥ 295 |
Schizophrenia has great human and economic costs.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) It decreases life expectancy by between 10[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13) and 28 years.[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) This is primarily because of its association with heart disease,[\[235\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kritharides2017-235) diabetes,[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) [obesity](https://en.wikipedia.org/wiki/Obesity "Obesity"), poor diet, a [sedentary lifestyle](https://en.wikipedia.org/wiki/Sedentary_lifestyle "Sedentary lifestyle"), and smoking, with an increased rate of suicide playing a lesser role.[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13)[\[236\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-236) Side effects of antipsychotics may also increase the risk.[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13)
Almost 40% of those with schizophrenia die from complications of cardiovascular disease which is seen to be increasingly associated.[\[232\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rastogi2020-232) An underlying factor of sudden cardiac death may be [Brugada syndrome](https://en.wikipedia.org/wiki/Brugada_syndrome "Brugada syndrome") (BrS) – BrS mutations that overlap with those linked with schizophrenia are the [calcium channel](https://en.wikipedia.org/wiki/Calcium_channel "Calcium channel") mutations.[\[232\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rastogi2020-232) BrS may also be drug-induced from certain antipsychotics and antidepressants.[\[232\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rastogi2020-232) [Primary polydipsia](https://en.wikipedia.org/wiki/Primary_polydipsia "Primary polydipsia"), or excessive fluid intake, is relatively common in people with chronic schizophrenia.[\[237\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-237)[\[238\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rizvi2019-238) This may lead to [hyponatremia](https://en.wikipedia.org/wiki/Hyponatremia "Hyponatremia") which can be life-threatening. Antipsychotics can lead to a [dry mouth](https://en.wikipedia.org/wiki/Xerostomia#Drug_induced_xerostomia "Xerostomia"), but there are several other factors that may contribute to the disorder; it may reduce life expectancy by 13 percent.[\[238\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Rizvi2019-238) Barriers to improving the mortality rate in schizophrenia are poverty, overlooking the symptoms of other illnesses, stress, stigma, and medication side effects.[\[239\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-239)[\[240\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:0-240)[\[241\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:1-241)
Schizophrenia is a major cause of [disability](https://en.wikipedia.org/wiki/Disability "Disability"). In 2016, it was classed as the 12th most disabling condition.[\[242\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-242) Approximately 75% of people with schizophrenia have ongoing disability with relapses.[\[243\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-243) Some people do recover completely and others function well in society.[\[244\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-244) Most people with schizophrenia live independently with community support.[\[28\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2009-28) About 85% are unemployed.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7) In people with a first episode of psychosis in schizophrenia a good long-term outcome occurs in 31%, an intermediate outcome in 42% and a poor outcome in 31%.[\[245\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-245) Males are affected more often than females, and have a worse outcome.[\[246\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-246) Studies showing that outcomes for schizophrenia appear better in the [developing](https://en.wikipedia.org/wiki/Developing_world "Developing world") than the [developed world](https://en.wikipedia.org/wiki/Developed_world "Developed world")[\[247\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Isa07-247) have been questioned.[\[248\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-248) Social problems, such as long-term unemployment, poverty, homelessness, exploitation, [stigmatization](https://en.wikipedia.org/wiki/Mental_disorder#Stigma "Mental disorder") and victimization are common consequences, and lead to [social exclusion](https://en.wikipedia.org/wiki/Social_exclusion "Social exclusion").[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26)[\[27\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Charleson2018-27)[\[240\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:0-240)[\[241\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:1-241)
There is a higher than average [suicide rate](https://en.wikipedia.org/wiki/Suicide_rate "Suicide rate") associated with schizophrenia estimated at 5% to 6%, most often occurring in the period following onset or first hospital admission.[\[19\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Ferri2019-19)[\[29\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jop2010-29) Several times more (20 to 40%) attempt suicide at least once.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10)[\[100\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Chiang2016-100) There are a variety of risk factors, including male sex, depression, a high [IQ](https://en.wikipedia.org/wiki/IQ "IQ"),[\[249\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-249) heavy smoking,[\[250\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-250) and substance use.[\[122\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Khokhar2018-122) Repeated relapse is linked to an increased risk of suicidal behavior.[\[188\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Taylor2019-188) The use of clozapine can reduce the risk of suicide, and of aggression.[\[251\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-251)
A strong association between [schizophrenia and tobacco smoking](https://en.wikipedia.org/wiki/Schizophrenia_and_tobacco_smoking "Schizophrenia and tobacco smoking") has been shown in worldwide studies.[\[252\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-252)[\[253\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Keltner2006-253) [Smoking](https://en.wikipedia.org/wiki/Tobacco_smoking "Tobacco smoking") is especially high in those diagnosed with schizophrenia, with estimates ranging from 80 to 90% being regular smokers, as compared to 20% of the general population.[\[253\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Keltner2006-253) Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content.[\[41\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSMIV-41) Some propose that this is in an effort to improve symptoms.[\[254\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-254) Among people with schizophrenia use of cannabis is also common.[\[122\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Khokhar2018-122)
Schizophrenia leads to an increased risk of dementia.[\[255\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-255)
Violence
Most people with schizophrenia are not aggressive, and are more likely to be victims of violence rather than perpetrators.[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) People with schizophrenia are commonly exploited and victimized by violent crime as part of a broader dynamic of social exclusion.[\[26\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Killaspy2014-26)[\[27\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Charleson2018-27) People diagnosed with schizophrenia are also subject to forced drug injections, seclusion, and restraint at high rates.[\[32\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BeckerKilian2006-32)[\[33\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Capdevielle2009-33)
The risk of violence by people with schizophrenia is small. There are minor subgroups where the risk is high.[\[173\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Richard-Devantoy2009-173) This risk is usually associated with a comorbid disorder such as a substance use disorder – in particular alcohol, or with antisocial personality disorder.[\[173\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Richard-Devantoy2009-173) Substance use disorder is strongly linked, and other risk factors are linked to deficits in cognition and social cognition including facial perception and insight that are in part included in [theory of mind](https://en.wikipedia.org/wiki/Theory_of_mind "Theory of mind") impairments.[\[256\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-256)[\[257\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-257) Poor cognitive functioning, decision-making, and facial perception may contribute to making a wrong judgement of a situation that could result in an inappropriate response such as violence.[\[258\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-258) These associated risk factors are also present in antisocial personality disorder which when present as a comorbid disorder greatly increases the risk of violence.[\[259\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-259)[\[260\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-260)
Epidemiology
[](https://en.wikipedia.org/wiki/File:Schizophrenia_world_map-Deaths_per_million_persons-WHO2012.svg)
Deaths per million persons due to schizophrenia in 2012
0–0
1–1
2–2
3–3
4–6
7–20
In 2017,\[*[needs update](https://en.wikipedia.org/wiki/Wikipedia:Manual_of_Style/Dates_and_numbers#Chronological_items "Wikipedia:Manual of Style/Dates and numbers")*\] the [Global Burden of Disease Study](https://en.wikipedia.org/wiki/Global_Burden_of_Disease_Study "Global Burden of Disease Study") estimated there were 1.1 million new cases;[\[21\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2018-21) in 2022 the World Health Organization (WHO) reported a total of 24 million cases globally.[\[2\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-WHO2022-2) Schizophrenia affects around 0.3–0.7% of people at some point in their life.[\[20\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Javitt2014-20)[\[14\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-NIHStat-14) In areas of conflict this figure can rise to between 4.0 and 6.5%.[\[261\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-261) It occurs 1.4 times more frequently in males than females and typically appears earlier in men.[\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86)
Worldwide, schizophrenia is the most common [psychotic disorder](https://en.wikipedia.org/wiki/Psychotic_disorder "Psychotic disorder").[\[57\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kar2016-57) The frequency of schizophrenia varies across the world,[\[10\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-DSM5-10) within countries,[\[262\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-262) and at the local and neighborhood level;[\[263\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-263) this variation in [prevalence](https://en.wikipedia.org/wiki/Prevalence "Prevalence") between studies over time, across geographical locations, and by gender is as high as fivefold.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)
Schizophrenia causes approximately one percent of worldwide [disability adjusted life years](https://en.wikipedia.org/wiki/Disability_adjusted_life_years "Disability adjusted life years")\[*[needs update](https://en.wikipedia.org/wiki/Wikipedia:Manual_of_Style/Dates_and_numbers#Chronological_items "Wikipedia:Manual of Style/Dates and numbers")*\][\[86\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-BMJ07-86) and resulted in 17,000 deaths in 2015.[\[16\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-GBD2015-16)
In 2000,\[*[needs update](https://en.wikipedia.org/wiki/Wikipedia:Manual_of_Style/Dates_and_numbers#Chronological_items "Wikipedia:Manual of Style/Dates and numbers")*\] WHO found the percentage of people affected and the number of new cases that develop each year is roughly similar around the world, with age-standardized prevalence per 100,000 ranging from 343 in Africa to 544 in Japan and Oceania for men, and from 378 in Africa to 527 in Southeastern Europe for women.[\[264\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-264)
History
Conceptual development
[](https://en.wikipedia.org/wiki/File:Eugen_bleuler.jpg)
The term "schizophrenia" was coined by [Eugen Bleuler](https://en.wikipedia.org/wiki/Eugen_Bleuler "Eugen Bleuler").
Accounts of a schizophrenia-like [syndrome](https://en.wikipedia.org/wiki/Syndrome "Syndrome") are rare in records before the 19th century; the earliest case reports were in 1797 and 1809.[\[265\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-265) The term *[dementia praecox](https://en.wikipedia.org/wiki/Dementia_praecox "Dementia praecox")* ("premature dementia") was used by German psychiatrist Heinrich Schüle in 1886 and then in 1891 by [Arnold Pick](https://en.wikipedia.org/wiki/Arnold_Pick "Arnold Pick") in a case report of [hebephrenia](https://en.wikipedia.org/wiki/Hebephrenia "Hebephrenia"). In 1893 [Emil Kraepelin](https://en.wikipedia.org/wiki/Emil_Kraepelin "Emil Kraepelin") used the term in making a distinction, known as the [Kraepelinian dichotomy](https://en.wikipedia.org/wiki/Kraepelinian_dichotomy "Kraepelinian dichotomy"), between the two psychoses: dementia praecox and [manic depression](https://en.wikipedia.org/wiki/Manic_depression "Manic depression") (now called [bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder")).[\[13\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Laursen2014-13) When it became evident that the disorder was not a degenerative dementia, it was renamed *schizophrenia* by [Eugen Bleuler](https://en.wikipedia.org/wiki/Eugen_Bleuler "Eugen Bleuler") in 1908.[\[266\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kuhn2004-266)
The word *schizophrenia* ("splitting of the mind") is [Modern Latin](https://en.wikipedia.org/wiki/Neo-Latin "Neo-Latin"), derived from the [Greek](https://en.wikipedia.org/wiki/Ancient_Greek "Ancient Greek") *schizein* ([Ancient Greek](https://en.wikipedia.org/wiki/Ancient_Greek_language "Ancient Greek language"): σχίζειν, [lit.](https://en.wikipedia.org/wiki/Literal_translation "Literal translation")'to split') and *phrēn* ([Ancient Greek](https://en.wikipedia.org/wiki/Ancient_Greek_language "Ancient Greek language"): φρήν, [lit.](https://en.wikipedia.org/wiki/Literal_translation "Literal translation")'mind').[\[267\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-267) Its use was intended to describe the separation of function between [personality](https://en.wikipedia.org/wiki/Personality_psychology "Personality psychology"), [thinking](https://en.wikipedia.org/wiki/Thought "Thought"), memory, and perception.[\[266\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Kuhn2004-266)
In the early 20th century, the psychiatrist [Kurt Schneider](https://en.wikipedia.org/wiki/Kurt_Schneider "Kurt Schneider") categorized the psychotic symptoms of schizophrenia into two groups: hallucinations and delusions. The hallucinations were listed as specific to auditory and the delusions included thought disorders. These were seen as important symptoms, termed [*first-rank*](https://en.wikipedia.org/wiki/Kurt_Schneider#First-rank_symptoms "Kurt Schneider"). The most common first-rank symptom was found to belong to thought disorders.\[*[page needed](https://en.wikipedia.org/wiki/Wikipedia:Citing_sources "Wikipedia:Citing sources")*\][\[268\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-268)\[*[page needed](https://en.wikipedia.org/wiki/Wikipedia:Citing_sources "Wikipedia:Citing sources")*\][\[269\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-269) In 2013 the first-rank symptoms were excluded from the DSM-5 criteria;[\[270\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-270) while they may not be useful in diagnosing schizophrenia, they can assist in [differential diagnosis](https://en.wikipedia.org/wiki/Differential_diagnosis "Differential diagnosis").[\[271\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-271)
Subtypes of schizophrenia—classified as paranoid, disorganized, [catatonic](https://en.wikipedia.org/wiki/Catatonia "Catatonia"), undifferentiated, and residual—were difficult to distinguish and are no longer recognized as separate conditions by DSM-5 (2013) or ICD-11.[\[272\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Reed2019-272)[\[273\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-273)[\[274\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-274)
Breadth of diagnosis
Before the 1960s, nonviolent [petty criminals](https://en.wikipedia.org/wiki/Petty_criminal "Petty criminal") and women were sometimes diagnosed with schizophrenia, categorizing the latter as ill for not performing their duties as wives and mothers.[\[275\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lane2010-275) In the mid- to late 1960s, black men were categorized as "hostile and aggressive" and diagnosed as schizophrenic at much higher rates, their [civil rights](https://en.wikipedia.org/wiki/Civil_rights_movement "Civil rights movement") and [Black Power](https://en.wikipedia.org/wiki/Black_Power "Black Power") activism labeled as delusions.[\[275\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lane2010-275)[\[276\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-276)
In the early 1970s in the United States, the diagnostic model for schizophrenia was broad and clinically based using [DSM II](https://en.wikipedia.org/wiki/DSM_II "DSM II"). Schizophrenia was diagnosed far more in the United States than in Europe, where the [ICD-9](https://en.wikipedia.org/wiki/ICD-9 "ICD-9") criteria were followed. The US model was criticised for failing to demarcate clearly those people with a mental illness. In 1980 DSM III was published and showed a shift in focus from the clinically based [biopsychosocial model](https://en.wikipedia.org/wiki/Biopsychosocial_model "Biopsychosocial model") to a reason-based medical model.\[*[clarification needed](https://en.wikipedia.org/wiki/Wikipedia:Please_clarify "Wikipedia:Please clarify")*\][\[277\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-277) DSM IV brought an increased focus on an evidence-based medical model.[\[278\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-278)
Historical treatment
[](https://en.wikipedia.org/wiki/File:Chlorpromazine-3D-vdW.png)
A molecule of [chlorpromazine](https://en.wikipedia.org/wiki/Chlorpromazine "Chlorpromazine"), the first antipsychotic developed in the 1950s
In the 1930s a number of shock procedures which induced seizures (convulsions) or comas were used to treat schizophrenia.[\[279\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jones2000-279) [Insulin shock](https://en.wikipedia.org/wiki/Insulin_shock_therapy "Insulin shock therapy") involved injecting large doses of [insulin](https://en.wikipedia.org/wiki/Insulin "Insulin") to induce comas, which in turn produced [hypoglycemia](https://en.wikipedia.org/wiki/Hypoglycemia "Hypoglycemia") and convulsions.[\[279\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Jones2000-279)[\[280\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-280) The use of electricity to induce seizures was in use as [electroconvulsive therapy](https://en.wikipedia.org/wiki/Electroconvulsive_therapy "Electroconvulsive therapy") (ECT) by 1938.[\[281\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-281)
Carried out from the 1930s until the 1970s in the United States and until the 1980s in France, [psychosurgery](https://en.wikipedia.org/wiki/Psychosurgery "Psychosurgery"), including such modalities as the [lobotomy](https://en.wikipedia.org/wiki/Lobotomy "Lobotomy"), is recognized as a [human rights abuse](https://en.wikipedia.org/wiki/Human_rights_abuse "Human rights abuse").[\[282\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-282)[\[283\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-283) In the mid-1950s, [chlorpromazine](https://en.wikipedia.org/wiki/Chlorpromazine "Chlorpromazine"), the first [typical antipsychotic](https://en.wikipedia.org/wiki/Typical_antipsychotic "Typical antipsychotic"), was introduced,[\[284\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-284) followed in the 1970s by clozapine, the first [atypical antipsychotic](https://en.wikipedia.org/wiki/Atypical_antipsychotic "Atypical antipsychotic").[\[285\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-285)
Political abuse
From the 1960s until 1989, psychiatrists in the [USSR](https://en.wikipedia.org/wiki/Soviet_Union "Soviet Union") and [Eastern Bloc](https://en.wikipedia.org/wiki/Eastern_Bloc "Eastern Bloc") diagnosed thousands of people with [sluggish schizophrenia](https://en.wikipedia.org/wiki/Sluggish_schizophrenia "Sluggish schizophrenia"),[\[286\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-286)[\[287\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-287) without signs of psychosis, based on "the assumption that symptoms would later appear".[\[288\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-288) Now discredited, the diagnosis provided a convenient way to confine political dissidents.[\[289\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Merskey1988-289)
Society and culture
In the United States, the annual cost of schizophrenia – including direct costs (outpatient, inpatient, drugs, and long-term care) and non-healthcare costs (law enforcement, reduced workplace productivity, and unemployment) – was estimated at \$62.7 billion for the year 2002.[\[290\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-290)[\[a\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-293) In the UK the cost in 2016 was put at £11.8 billion per year with a third of that figure directly attributable to the cost of hospital, social care and treatment.[\[7\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Lancet2016-7)
Stigma
[](https://en.wikipedia.org/wiki/File:John_Forbes_Nash,_Jr._by_Peter_Badge.jpg)
[John Nash](https://en.wikipedia.org/wiki/John_Forbes_Nash "John Forbes Nash"), an American mathematician and joint recipient of the 1994 [Nobel Memorial Prize in Economic Sciences](https://en.wikipedia.org/wiki/Nobel_Memorial_Prize_in_Economic_Sciences "Nobel Memorial Prize in Economic Sciences"), had schizophrenia. His life was the subject of the 1998 book, *[A Beautiful Mind](https://en.wikipedia.org/wiki/A_Beautiful_Mind_\(book\) "A Beautiful Mind (book)")*, by [Sylvia Nasar](https://en.wikipedia.org/wiki/Sylvia_Nasar "Sylvia Nasar").
In 2002, the term for schizophrenia in Japan was changed from *seishin-bunretsu-byō* (精神分裂病; lit. 'mind-split disease') to *tōgō-shitchō-shō* (統合失調症; lit. 'integration–dysregulation syndrome') to reduce [stigma](https://en.wikipedia.org/wiki/Social_stigma "Social stigma") and confusion with "multiple personalities".[\[293\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-294) The new name, also interpreted as "integration disorder", was inspired by the biopsychosocial model.[\[294\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-295) A similar change was made in South Korea in 2012 to attunement disorder.[\[295\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-296)
Stigma may prevent further research and treatment as in history treated some in the past invariably worse to recovery.[\[240\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:0-240)[\[241\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:1-241)
Cultural depictions
Media coverage, especially movies, reinforce the public perception of an association between schizophrenia and violence.[\[296\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-297)[\[241\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:1-241)[\[240\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-:0-240) A majority of movies have historically depicted characters with schizophrenia as criminal, dangerous, violent, unpredictable and homicidal, and depicted delusions and hallucinations as the main symptoms of schizophrenic characters, ignoring other common symptoms,[\[297\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Owen2012-298) furthering stereotypes of schizophrenia including the idea of a split personality.[\[298\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-299)
The book *[A Beautiful Mind](https://en.wikipedia.org/wiki/A_Beautiful_Mind_\(book\) "A Beautiful Mind (book)")* chronicled the life of [John Forbes Nash](https://en.wikipedia.org/wiki/John_Forbes_Nash "John Forbes Nash") who had been diagnosed with schizophrenia and won the [Nobel Memorial Prize in Economic Sciences](https://en.wikipedia.org/wiki/Nobel_Memorial_Prize_in_Economic_Sciences "Nobel Memorial Prize in Economic Sciences"). The book was made into a [film with the same name](https://en.wikipedia.org/wiki/A_Beautiful_Mind_\(film\) "A Beautiful Mind (film)"); an earlier documentary film was *[A Brilliant Madness](https://en.wikipedia.org/wiki/A_Brilliant_Madness "A Brilliant Madness")*.
In the UK, guidelines for reporting conditions and award campaigns have shown a reduction in negative reporting since 2013.[\[299\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-300)
In 1964 a [case study](https://en.wikipedia.org/wiki/Case_study "Case study") of three males diagnosed with schizophrenia who each had the delusional belief that they were [Jesus Christ](https://en.wikipedia.org/wiki/Jesus "Jesus") was published as *[The Three Christs of Ypsilanti](https://en.wikipedia.org/wiki/The_Three_Christs_of_Ypsilanti "The Three Christs of Ypsilanti")*; a film with the title *[Three Christs](https://en.wikipedia.org/wiki/Three_Christs "Three Christs")* was released in 2020.[\[300\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-301)[\[301\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-302)
Research
A 2015 Cochrane review found unclear evidence of benefit from brain stimulation techniques to treat the positive symptoms of schizophrenia, in particular auditory verbal hallucinations (AVHs).[\[302\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-303) Most studies focus on [transcranial direct-current stimulation](https://en.wikipedia.org/wiki/Transcranial_direct-current_stimulation "Transcranial direct-current stimulation") (tDCM), and [repetitive transcranial magnetic stimulation](https://en.wikipedia.org/wiki/Repetitive_transcranial_magnetic_stimulation "Repetitive transcranial magnetic stimulation") (rTMS).[\[303\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Nathou2019-304) Techniques based on focused ultrasound for [deep brain stimulation](https://en.wikipedia.org/wiki/Deep_brain_stimulation "Deep brain stimulation") could provide insight for the treatment of AVHs.[\[303\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Nathou2019-304)
The study of potential [biomarkers](https://en.wikipedia.org/wiki/Biomarker_\(medicine\) "Biomarker (medicine)") that would help in diagnosis and treatment of schizophrenia is an active area of research as of 2020. Possible biomarkers include markers of inflammation,[\[99\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Upthegrove2020-99) [neuroimaging](https://en.wikipedia.org/wiki/Functional_MRI_methods_and_findings_in_schizophrenia "Functional MRI methods and findings in schizophrenia"),[\[304\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-305) [brain-derived neurotrophic factor](https://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor "Brain-derived neurotrophic factor") (BDNF),[\[305\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-306) and speech analysis. Some markers such as [C-reactive protein](https://en.wikipedia.org/wiki/C-reactive_protein "C-reactive protein") are useful in detecting levels of inflammation implicated in some psychiatric disorders but they are not disorder-specific. Other inflammatory cytokines are found to be elevated in first episode psychosis and acute relapse that are normalized after treatment with antipsychotics, and these may be considered as state markers.[\[306\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-307) Deficits in [sleep spindles](https://en.wikipedia.org/wiki/Sleep_spindle "Sleep spindle") in schizophrenia may serve as a marker of an impaired thalamocortical circuit, and a mechanism for memory impairment.[\[175\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-Pocivavsek2018-175) [MicroRNAs](https://en.wikipedia.org/wiki/MicroRNA "MicroRNA") are highly influential in early neuronal development, and their disruption is implicated in several [CNS](https://en.wikipedia.org/wiki/Central_nervous_system "Central nervous system") disorders; [circulating microRNAs](https://en.wikipedia.org/wiki/Circulating_microRNA "Circulating microRNA") (cimiRNAs) are found in [body fluids](https://en.wikipedia.org/wiki/Body_fluid "Body fluid") such as blood and cerebrospinal fluid, and changes in their levels are seen to relate to changes in microRNA levels in specific regions of brain tissue. These studies suggest that cimiRNAs have the potential to be early and accurate biomarkers in a number of disorders including schizophrenia.[\[307\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-308)[\[308\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-309)
[Ongoing fMRI research](https://en.wikipedia.org/wiki/Functional_MRI_methods_and_findings_in_schizophrenia "Functional MRI methods and findings in schizophrenia") aims to identify biomarkers within these brain networks,[\[309\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-310) potentially aiding in earlier diagnosis and better tracking of treatment responses in schizophrenia.
Explanatory notes
1. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-293)** A 2007 review stated that the 2002 estimate was still the best available,[\[291\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-291) and a 2018 review cited the same \$62.7 billion.[\[292\]](https://en.wikipedia.org/wiki/Schizophrenia#cite_note-292)
References
1. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-1)**
[Jones D](https://en.wikipedia.org/wiki/Daniel_Jones_\(phonetician\) "Daniel Jones (phonetician)") (2003) \[1917\]. Roach P, Hartmann J, Setter J (eds.). *English Pronouncing Dictionary*. Cambridge University Press. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)")
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["Schizophrenia Fact sheet"](https://www.who.int/news-room/fact-sheets/detail/schizophrenia). [World Health Organization](https://en.wikipedia.org/wiki/World_Health_Organization "World Health Organization"). 10 January 2022. Retrieved 23 August 2022.
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["Schizophrenia"](https://www.nimh.nih.gov/health/topics/schizophrenia). *Health topics*. US [National Institute of Mental Health](https://en.wikipedia.org/wiki/National_Institute_of_Mental_Health "National Institute of Mental Health"). April 2022. Retrieved 22 August 2022.
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["Medicinal treatment of psychosis/schizophrenia"](http://www.sbu.se/en/publications/sbu-assesses/schizophrenia--pharmacological-treatments-patient-involvement-and-organization-of-care/). [Swedish Agency for Health Technology Assessment and Assessment of Social Services](https://en.wikipedia.org/wiki/Swedish_Agency_for_Health_Technology_Assessment_and_Assessment_of_Social_Services "Swedish Agency for Health Technology Assessment and Assessment of Social Services") (SBU). 21 November 2012. [Archived](https://web.archive.org/web/20170629092226/http://www.sbu.se/en/publications/sbu-assesses/schizophrenia--pharmacological-treatments-patient-involvement-and-organization-of-care/) from the original on 29 June 2017. Retrieved 26 June 2017.
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Proietto Sr J (November 2004). ["Diabetes and Antipsychotic Drugs"](https://www.medsafe.govt.nz/profs/puarticles/antipsychdiabetes.htm). [Medsafe](https://en.wikipedia.org/wiki/Medsafe "Medsafe").
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Holt RI (September 2019). ["Association Between Antipsychotic Medication Use and Diabetes"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718373). *Current Diabetes Reports*. **19** (10) 96. [National Center for Biotechnology Information](https://en.wikipedia.org/wiki/National_Center_for_Biotechnology_Information "National Center for Biotechnology Information"). [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s11892-019-1220-8](https://doi.org/10.1007%2Fs11892-019-1220-8). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1534-4827](https://search.worldcat.org/issn/1534-4827). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6718373](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718373). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31478094](https://pubmed.ncbi.nlm.nih.gov/31478094).
7. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-3) [***e***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-4) [***f***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-5) [***g***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-6) [***h***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-7) [***i***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-8) [***j***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-9) [***k***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-10) [***l***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-11) [***m***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-12) [***n***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-13) [***o***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-14) [***p***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Lancet2016_7-15)
Owen MJ, Sawa A, Mortensen PB (July 2016). ["Schizophrenia"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940219). *The Lancet*. **388** (10039): 86–97\. [Bibcode](https://en.wikipedia.org/wiki/Bibcode_\(identifier\) "Bibcode (identifier)"):[2016Lanc..388...86O](https://ui.adsabs.harvard.edu/abs/2016Lanc..388...86O). [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S0140-6736(15)01121-6](https://doi.org/10.1016%2FS0140-6736%2815%2901121-6). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4940219](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940219). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [26777917](https://pubmed.ncbi.nlm.nih.gov/26777917).
8. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-8)**
Sara G, Large M, Lappin J, Murrie B (May 2020). ["Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis"](https://academic.oup.com/schizophreniabulletin/article/46/3/505/5588638). *[Schizophrenia Bulletin](https://en.wikipedia.org/wiki/Schizophrenia_Bulletin "Schizophrenia Bulletin")*. **46** (3): 505–516\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1093/schbul/sbz102](https://doi.org/10.1093%2Fschbul%2Fsbz102). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7147575](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147575). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31618428](https://pubmed.ncbi.nlm.nih.gov/31618428).
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Gruebner O, Rapp MA, Adli M, Kluge U, Galea S, Heinz A (February 2017). ["Cities and Mental Health"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374256). *Deutsches Ärzteblatt International*. **114** (8): 121–127\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3238/arztebl.2017.0121](https://doi.org/10.3238%2Farztebl.2017.0121). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5374256](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374256). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [28302261](https://pubmed.ncbi.nlm.nih.gov/28302261).
10. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-3) [***e***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-4) [***f***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-5) [***g***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-6) [***h***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-7) [***i***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-8) [***j***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-9) [***k***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-10) [***l***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-11) [***m***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-12) [***n***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-13) [***o***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-14) [***p***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-15) [***q***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-16) [***r***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-17) [***s***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-18) [***t***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-19) [***u***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-DSM5_10-20)
*Diagnostic and Statistical Manual of Mental Disorders: DSM-5* (5th ed.). Arlington, VA: American Psychiatric Association. 2013. pp. 99–105\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)")
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11. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Ferri2010_11-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Ferri2010_11-1)
Ferri FF (2010). "Chapter S". *Ferri's differential diagnosis: a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders* (2nd ed.). Philadelphia: Elsevier/Mosby. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)")
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12. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Paris2018_12-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Paris2018_12-1)
Paris J (December 2018). "Differential Diagnosis of Borderline Personality Disorder". *The Psychiatric Clinics of North America*. **41** (4): 575–582\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.psc.2018.07.001](https://doi.org/10.1016%2Fj.psc.2018.07.001). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [30447725](https://pubmed.ncbi.nlm.nih.gov/30447725). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [53951650](https://api.semanticscholar.org/CorpusID:53951650).
13. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Laursen2014_13-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Laursen2014_13-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Laursen2014_13-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Laursen2014_13-3) [***e***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Laursen2014_13-4) [***f***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-Laursen2014_13-5)
Laursen TM, Nordentoft M, Mortensen PB (2014). ["Excess early mortality in schizophrenia"](https://doi.org/10.1146%2Fannurev-clinpsy-032813-153657). *Annual Review of Clinical Psychology*. **10**: 425–448\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1146/annurev-clinpsy-032813-153657](https://doi.org/10.1146%2Fannurev-clinpsy-032813-153657). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [24313570](https://pubmed.ncbi.nlm.nih.gov/24313570).
14. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-2) [***d***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-3) [***e***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-NIHStat_14-4)
["Schizophrenia"](https://www.nimh.nih.gov/health/statistics/schizophrenia). *Statistics*. US [National Institute of Mental Health](https://en.wikipedia.org/wiki/National_Institute_of_Mental_Health "National Institute of Mental Health") (NIMH). 22 April 2022. Retrieved 23 August 2022.
15. **[^](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-WHO_FACT_SHEET_15-0)**
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16. ^ [***a***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-GBD2015_16-0) [***b***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-GBD2015_16-1) [***c***](https://en.wikipedia.org/wiki/Schizophrenia#cite_ref-GBD2015_16-2)
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External links
- [Schizophrenia: Evolution and Synthesis](https://direct.mit.edu/books/oa-edited-volume/5036/SchizophreniaEvolution-and-Synthesis)
- [The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia, Third Edition](https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890424841) |
| Shard | 152 (laksa) |
| Root Hash | 17790707453426894952 |
| Unparsed URL | org,wikipedia!en,/wiki/Schizophrenia s443 |