Schizophrenia in Adults - Epidemiology and Pathogenesis - UpToDate PDF

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Schizophrenia in adults: Epidemiology and pathogenesis

Authors: Bernard A Fischer, MD, Robert W Buchanan, MD
Section Editor: Stephen Marder, MD
Deputy Editor: Richard Hermann, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2019. | This topic last updated: Mar 13, 2019.
INTRODUCTION
Schizophrenia is among the most disabling and economically catastrophic medical disorders, ranked
by the World Health Organization as one of the top 10 illnesses contributing to the global burden of
disease [1].
Characteristics of schizophrenia typically include positive symptoms, such as hallucinations or

delusions; disorganized speech; negative symptoms, such as a flat affect or poverty of speech; and
impairments in cognition, including attention, memory, and executive functions. The illness is
commonly associated with impairments in social and occupational functioning [2]. Antipsychotic
medications are the first-line treatment for schizophrenia. Evidence-based psychosocial interventions
in conjunction with pharmacotherapy can help patients achieve recovery.
This topic discusses the epidemiology and pathogenesis of schizophrenia. Clinical manifestations,
assessment, diagnosis, and course of schizophrenia are discussed separately. Anxiety and
depression in schizophrenia are discussed separately. Psychosocial and pharmacologic treatments
for schizophrenia are discussed separately, including long-acting antipsychotics, clozapine, and
management of antipsychotic side effects. Evaluation and management of treatment resistant
schizophrenia are also reviewed separately. (See "Schizophrenia in adults: Clinical manifestations,
course, assessment, and diagnosis" and "Pharmacotherapy for schizophrenia: Acute and
maintenance phase treatment" and "Pharmacotherapy for schizophrenia: Side effect management"
and "Pharmacotherapy for schizophrenia: Long-acting injectable antipsychotic drugs" and
"Psychosocial interventions for schizophrenia" and "Depression in schizophrenia" and "Anxiety in
schizophrenia" and "Evaluation and management of treatment-resistant schizophrenia".)
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EPIDEMIOLOGY
Schizophrenia occurs throughout the world. The prevalence of schizophrenia (ie, the number of cases
in a population at any one time point) approaches 1 percent internationally. The incidence (the
number of new cases annually) is about 1.5 per 10,000 people [3]. Age of onset is typically during
adolescence; childhood and late-life onset (over 45 years) are rare. Slightly more men are diagnosed
with schizophrenia than women (on the order of 1.4:1) [4], and women tend to be diagnosed later in
life than men. Modal age of onset is between 18 and 25 for men and between 25 and 35 for women,
with a second peak occurring around menopause [5]. There is also some indication that the prognosis
is worse in men [6,7].
Co-occurring conditions — People with schizophrenia have higher rates of several psychiatric
disorders than people without schizophrenia, including:
● Depressive disorders (see "Depression in schizophrenia")
● Anxiety disorders: social anxiety disorder, posttraumatic stress disorder, and obsessive-
compulsive disorder (see "Anxiety in schizophrenia")
● Alcohol and other substance use disorders (see "Co-occurring schizophrenia and substance use
disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment and
diagnosis")
People with schizophrenia are also at greater risk for co-occurring conditions, such as metabolic and
neurological problems. (See "Schizophrenia in adults: Clinical manifestations, course, assessment,
and diagnosis", section on 'Associated physical manifestations'.)
Risk factors — A number of epidemiologic risk factors have been associated with the development of
schizophrenia, including:
● Living in an urban area [8,9]
● Immigration [10,11]
● Obstetrical complications [12]
● Late winter-early spring birth – Perhaps reflecting exposure to influenza virus during neural
development
● Advanced paternal age at conception [13] – May be associated with an increased risk of de novo
mutations [14]

Environmental risk factors for schizophrenia are discussed below. (See 'Environmental risk factors'
below.)
Cost — The cost of schizophrenia is staggering. The overall cost of schizophrenia in the United
States in 2002 was estimated at about $63 billion [15]. This figure includes direct healthcare costs and
indirect costs associated with loss of productivity. A study comparing the cost of schizophrenia in India
in 2001 with the cost in the same catchment area in 2011 found that the cost had doubled in those 10
years, mainly related to increases in indirect costs [16]. A study examining United States insurance
claims found that the annual health-related expenses of someone with chronic schizophrenia
averaged more than $15,000 [17]. The cost of schizophrenia treatment from 2004 to 2009 to
Medicare in the United States increased from $9.4 billion to $11.5 billion [18].
Deficit schizophrenia — Deficit schizophrenia, characterized by primary, enduring negative

symptoms, seems to be a specific disease process within the larger syndrome of schizophrenia.
Approximately 15 to 20 percent of the total schizophrenia population has the deficit form of
schizophrenia [19-22]. They are more likely to be male and more likely to have relatives with
schizophrenia than people with nondeficit schizophrenia [23-27]. As opposed to the excess of late
winter-early spring births observed in schizophrenia in general, there is a disproportionate rate of
summer births in the deficit group [19,28]. Examples of negative symptoms include decreased
expressiveness, apathy, flat affect, and a lack of energy. People with deficit schizophrenia are less
likely to have addictions, depression, suicidality, or delusions with high emotional content (such as
jealous delusions) compared to nondeficit schizophrenia [29-31]. (See "Schizophrenia in adults:
Clinical manifestations, course, assessment, and diagnosis", section on 'Deficit schizophrenia'.)
PATHOGENESIS
Although the pathogenesis of the disorder is unknown, it is almost certain that schizophrenia
represents a syndrome comprised of multiple diseases that present with similar signs and symptoms
[32]. This heterogeneity complicates the elucidation of the etiological and pathophysiological factors
that underlie the group of disorders. Schizophrenia appears to be a uniquely human condition, which
limits the utility of animal models [33]. There is little doubt that schizophrenia proceeds from a
complex interaction between genes and the environment, but even the attempt to differentiate genetic
from environmental risk factors may be artificial, since environmental factors can influence gene
expression just as a person’s genetic make-up can influence response to environmental stressors.
Research studies have found the following genetic and environmental risk factors in schizophrenia,
which may act through disrupted neurotransmitter system function.

Genetic risk factors — Twin studies have been conducted in monozygotic and dizygotic twins to
examine concordance rates of schizophrenia within the twin pairs. The observed concordance rate in
monozygotic twins, who share 100 percent of their genes, is about 40 to 50 percent, whereas the
observed concordance rate in dizygotic twins, who share 50 percent of their genes, is about 10 to 15
percent. [34-36]. The increased concordance rate of schizophrenia in monozygotic compared to
dizygotic twins suggests a strong genetic component to schizophrenia. The offspring of the unaffected
monozygotic twins are at increased risk of schizophrenia, which further supports the existence of a
genetic predisposition for the illness. The fact that the monozygotic twin concordance rate is less than
100 percent, however, suggests that nongenetic, environmental factors are also involved in the
development of the illness [34-36]. Adoption studies have provided further evidence for the presence
of genetic risk factors.
Although there is abundant evidence for genetic risk factors, the specific genes involved in the
etiology of schizophrenia have not been identified. Initial studies have used genetic linkage or
candidate gene approaches to identify several specific genes as candidates for a role in the
development of schizophrenia (table 1).
The mapping of the human genome has allowed for the study of associations between gene variants
and risk or occurrence of diseases, ie, genome-wide association studies (GWAS). The results of
GWAS of schizophrenia support a polygenic model, in which multiple genes with additive small effects
lead to the disorder. As many as 500,000 single nucleotide polymorphisms (SNPs) have been tested
in GWAS for association with schizophrenia. In a study of over 35,000 cases and 110,00 controls, 108
SNPs were found to have a significant association with schizophrenia [37]. The identified genetic loci
supported the involvement of the dopaminergic and glutamatergic neurotransmitter systems in the
pathophysiology of schizophrenia. The study also replicated previous studies that have shown an
association between genes of the major histocompatibility complex (MHC), which support immune
functions, and schizophrenia. A 2016 study of the MHC locus demonstrated that expression of
complement component 4 allele A (C4A) was proportional to the risk of having schizophrenia [38]. C4
expression and activity were then tested in mouse models and shown to be related to adolescent
pruning of brain synapses. These findings are consistent with decreased “neuropil,” or dendritic
density, which has been reliably observed in people with schizophrenia [39]. (See "Genetic
association and GWAS studies: Principles and applications".)
Another attempt to delineate the genetics of schizophrenia is the evaluation of copy number variants
(CNVs), which are genes that have been duplicated or deleted. People with schizophrenia have been
found to have higher rates of CNVs. The most frequent CNV associated with schizophrenia is a
deletion on the long arm of chromosome 22 (22q11) [40]. (See "Genetic association and GWAS
studies: Principles and applications".)

Environmental risk factors
Obstetrical complications — Various perinatal problems, grouped together for analysis as

“obstetrical complications,” increase the risk of later development of schizophrenia two-fold [12].
These perinatal problems include:
● Hemorrhage
● Preterm labor
● Blood-group incompatibilities
● Fetal hypoxia
● Maternal infection (see 'Infections' below)
The accuracy of these data, based on maternal recall many years after childbirth, has been
questioned, but studies suggest that the risk does not appear to be influenced by inaccurate
memories [41,42]. The association between obstetrical complications and the development of
schizophrenia has also been observed in data from medical records, which do not rely on recall [12].
In studies based on subsequent hospital records, pregnancy during famines in the Netherlands (1944
through 1945) [43] and in China (1959 through 1961) [44,45] has been associated with a two-fold risk
of schizophrenia in the offspring. The results of these studies indicate that maternal nutrition is a
factor in the development of schizophrenia. Other, related factors associated with an increased risk of
subsequently developing schizophrenia include being the product of an unwanted pregnancy [46] and
the prenatal death of the father [47].
Increased prenatal maternal stress has been proposed as the common pathophysiological
mechanism underlying risk factors, such as famine, bereavement, and antenatal infection. An animal
model provides some support for this theory [48].
Infections — Several epidemiologic findings have suggested a possible role of certain infectious
agents as potential risk factors for the development of schizophrenia:
● Numerous epidemiological studies have found an increase in schizophrenia prevalence in

cohorts born during influenza epidemics [49].
• The increased risk for schizophrenia among those born in the late winter-early spring could
possibly reflect increased maternal exposure to influenza virus during prenatal neural
development.
● High maternal IgG antibodies to the parasite toxoplasma gondii have been found to increase the
relative risk of developing schizophrenia in offspring by about 60 to 70 percent [50,51].

● Studies have varied on whether herpes simplex virus type 2 maternal infection increases the risk
for schizophrenia; some studies have found increased risks between 60 percent to more than
400 percent [52,53], while other studies have found no increased risk [54].
● Other infectious agents associated with schizophrenia appear to have an influence outside the
model of perinatal exposure of the affected individual. As examples:
• Higher maternal levels of IgG to toxoplasma gondii are related to the later development of
schizophrenia in the mother herself [55].
• Measles antibodies are higher in people with schizophrenia, especially in those with recent-
onset of psychosis, than controls [56].
• Bacterial infections during childhood, which lead to hospitalization, are related to an

increased risk for developing schizophrenia [57,58].
The mechanism by which infections increase the risk of schizophrenia is unclear. There is little
evidence to suggest that the risk is associated with direct damage by the infectious agent to the
central nervous system (CNS). A study comparing individuals hospitalized for meningitis as children
to a control group who were hospitalized with gastroenteritis as children found no difference in the risk
of later hospitalization for schizophrenia [59]. A more likely explanation is that infection by certain
agents triggers an immune response in a mother that is passed through the placenta to the
developing fetus, which compromises the blood brain barrier and allows antibodies, which cross-react
with CNS proteins, to enter into the developing nervous system [60]. Early childhood infections could
also initiate an immune response and lead to a general state of increased inflammation. (See
'Inflammation' below.)
Inflammation — Increased immune system activation leads to higher levels of circulating pro-
inflammatory cytokines. Increased pro-inflammatory cytokine levels have been frequently observed in
schizophrenia [61]. Cytokines can alter the blood-brain barrier, or be produced locally in the CNS by
activated microglia, and may be responsible for psychosis, its exacerbation, or cognitive impairments
[62]. The actions of antipsychotic drugs may be partially mediated by the anti-inflammatory effects of
these agents [63].
In addition to associations between schizophrenia and some infections, there is other evidence for
abnormal immune activation in people with schizophrenia. (See 'Infections' above.)
Autoimmune disorders that have been associated with a higher prevalence of schizophrenia include
[64,65]:
● Acquired hemolytic anemia

● Bullous pemphigoid
● Celiac disease
● Interstitial cystitis
● Thyrotoxicosis
(A notable exception is rheumatoid arthritis, in which schizophrenia rates are lower than expected
based on rates in the general population [66]. People with schizophrenia are also more likely to have
circulating antibodies to proteins common in most Western diets, such as gluten [67,68] and casein
[69,70].)
Clinical trials of anti-inflammatory agents for psychosis have been spurred, in part, by these findings.
Inflammation in people with schizophrenia may also be responsible for some of the disorder’s
associated conditions such as heart disease (through decreased elasticity of inflamed blood vessels)
and diabetes (See "Schizophrenia in adults: Clinical manifestations, course, assessment, and
diagnosis", section on 'Metabolic disturbances'.)
Cannabis use — Epidemiological studies suggest that cannabis use is a risk factor for the
development of psychosis [71-73]. Initial findings from retrospective studies were inconclusive
because people with psychotic disorders, even before they were diagnosed, could be using cannabis.
This would indicate that psychosis was a risk factor for using cannabis rather than the reverse. Well-
controlled, prospective studies following hundreds of people have subsequently supported the
hypothesis that cannabis use is the risk factor and psychosis the result [74,75]. The increased risk
posed by cannabis use depends on other risk factors, such as family history, but is generally reported
with odds ratios of 2.2 to 2.8 [72,74,75]. Acute infusions of delta-9-tetrahydrocannabinol have
provoked psychotic-like symptoms in people with and without schizophrenia [76,77], providing further
evidence for cannabis as a risk factor for psychosis. (See "Cannabis use and disorder: Epidemiology,
comorbidity, health consequences, and medico-legal status".)
In contrast to the psychotomimetic properties of delta-9-tetrahydrocannabinol, the cannabis ingredient

cannabidiol (CBD) has been shown to attenuate psychotic symptoms [78,79]. The mechanism by
which CBD exerts this potential effect is unknown.
CBD may exert its potential therapeutic effects through modulation of the level of activity of various
brain regions previously shown to be associated with schizophrenia pathology. In a 2018
neuroimaging study, individuals at clinical high risk of psychosis were randomized to either a single
dose of CBD (600 mg) or placebo. The placebo group had reduced activation compared with matched
controls in the caudate during memory encoding and in the parahippocampal gyrus and midbrain
during recall [80]. In contrast, the CBD group showed increased activity of these regions compared

with the placebo-treated group, but the level of activation was still less than what was observed in a
group of healthy controls.
Both groups (placebo- and cannabidiol-treated) had lifetime histories of cannabis use (100 and 94
percent, respectively) and current use (41 and 44 percent, respectively) while the healthy controls did
not (less than 10 times lifetime use and no current use), which may affect the interpretation of the
study results.
Cigarette smoking — Studies of the effect of cigarette smoking during pregnancy on the risk for
the development of schizophrenia have been mixed. The first study to use serum cotinine as a
biomarker for smoking, however, found cigarette smoking during pregnancy significantly increases the
odds of schizophrenia in the offspring (odds ratio = 3.41, 95% CI 1.86-6.24). This study was based on
a Finnish national health registry and included 977 cases of schizophrenia [81].
Although this finding could be related to nicotinic acetylcholine perturbations during development or
fetal hypoxia, it may simply reflect genetic risk. It is well known that first-degree relatives of people
with schizophrenia have higher rates of smoking compared with the relatives of healthy controls [82].
Immigration — Numerous studies in multiple countries have observed a higher prevalence of

schizophrenia in immigrant populations compared with native-born populations [10,11]. This increased
relative risk can be as high as four-fold, depending on the study. An increased risk appears to extend
to second-generation immigrants as well [11].
Several possible explanations for the association between immigrants and schizophrenia have been
proposed:
● Schizophrenia may be overdiagnosed in immigrant populations; however, further research

suggests that this cannot entirely explain the increase in risk observed [83].
● In people with either a genetic or neurodevelopmental biological risk for schizophrenia, stress can
play a role in the ultimate development of the disorder. In this way, the stress of immigration,
becoming part of an outsider group, may contribute to the development of schizophrenia. Studies
have found associations between the amount of social discrimination experienced by immigrant
groups and the rates of schizophrenia in the group; that is, immigrant groups experiencing more
discrimination have higher rates of schizophrenia than immigrant groups experiencing lower rates
of social discrimination. This finding has been observed in several immigrant groups in several
countries:
• Ethiopian immigrants to Israel [84]

• Moroccan immigrants to Holland [11]
• Caribbean immigrants to the United Kingdom [85]
● The increased risk of schizophrenia in immigrants may be related to vitamin D deficiency,

especially among individuals who move to more northern latitudes [86].
Neurotransmitters
Dopamine — All drugs with antipsychotic properties block the dopaminergic D2 receptor, a finding
that has led to the dopamine hypothesis of schizophrenia, in which excess dopamine in the
mesolimbic tract has been hypothesized to cause positive psychotic symptoms. However, if dopamine
were the sole neurotransmitter disrupted in schizophrenia, then antipsychotics would be universally
and completely effective for these symptoms. However, despite adequate antipsychotic treatment,
many people with schizophrenia continue to exhibit positive symptoms. Therefore, it is likely that
dysfunction in other neurotransmitter systems is required to explain why many people with the illness
exhibit only a partial reduction in positive symptoms, and why clozapine, the most efficacious
antipsychotic in schizophrenia, is a weak D2 antagonist.
Decreased dopamine in the prefrontal cortex (largely affecting the D1 receptor) may be responsible
for some of the cognitive and negative symptoms observed in schizophrenia [87,88]. (See
"Schizophrenia in adults: Clinical manifestations, course, assessment, and diagnosis", section on
'Clinical manifestations'.)
Glutamate — Glutamate is the major CNS excitatory neurotransmitter. Hypofunction of the N-

methyl-D-aspartate (NMDA) glutamate receptor has been hypothesized to contribute to the pathology
of schizophrenia [89]. Evidence comes from:
● Clinical observations of people who have misused phencyclidine (a NMDA receptor antagonist)
● Challenge studies using ketamine (a NMDA receptor antagonist) [90-92]
● Genetic findings [89]
● Post-mortem studies [93]
● Studies measuring the level of endogenous NMDA receptor antagonists in the CNS of people
with schizophrenia [94,95]
Clinical trials with agents that enhance glutamatergic neurotransmission have had varied results
depending on the mechanism of the agent used [96,97]. (See "Pharmacotherapy for schizophrenia:
Acute and maintenance phase treatment".)
Gamma-amino-butyric acid — Gamma-amino-butyric acid (GABA) is the major CNS inhibitory

neurotransmitter. GABAergic interneurons are important for regulation of prefrontal cortical function,

through their modulation of glutamatergic pyramidal cells. Several lines of evidence suggest that
these interneurons are dysfunctional in people with schizophrenia [98-103].
● Postmortem studies in people with schizophrenia have found decreased levels of glutamic acid
decarboxylase (GAD67) mRNA expression in the prefrontal cortex [104].
● In people with schizophrenia with decreased GAD67, there is a decrease in the density of
chandelier cell connections with the pyramidal cell axon initial segment [104] and in the
immunoreactivity of the GABA plasma membrane transporter-1 in chandelier cell axon terminals
[104].
● There appears to be a decrease in GABA reuptake transporter mRNA levels [104] and an
increase in GABAA alpha-2 subunit density on the axon initial segment [104], both of which may
be compensatory shifts.
Acetylcholine — The increased smoking behaviors observed in people with schizophrenia [105-
108] has led to the hypothesis that nicotine, which stimulates a subset of acetylcholine receptors, is
correcting a fundamental neurochemical problem in schizophrenia. Treatment with nicotine or a
nicotinic cholinergic drug can normalize some eye-tracking and EEG abnormalities observed in
people with schizophrenia [109-113] and may acutely improve some aspects of cognition [114,115].
However, nicotinic acetylcholine receptors can affect many other neurotransmitter systems (for
example, nicotine can enhance current mediated by glutamate receptors in dopamine neurons of the
rat ventral tegmentum [116,117]), and so it is not clear whether the cholinergic system is primarily
disrupted in schizophrenia or the disruption is secondary to other pathological characteristics of the
illness.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Psychotic disorders".)
SUMMARY AND RECOMMENDATIONS
● Schizophrenia has a worldwide prevalence approaching 1 percent, with an incidence of about 1.5
new cases annually per 10,000 people. (See 'Epidemiology' above.)
● People with schizophrenia have higher rates of depression, several anxiety disorders, substance
use disorders, and suicide compared to people without schizophrenia. (See 'Co-occurring
conditions' above.)
https://www-uptodate-com.unicartagena.basesdedatosezproxy.com/contents/schizophrenia-in-adults-epidemiology-and-pathogenesis/print?search=esquizofrenia fis… 10/22
● Approximately 15 to 20 percent of patients with schizophrenia have the deficit form of

schizophrenia, characterized by primary, enduring negative symptoms such as decreased
expressiveness, apathy, flat affect, and a lack of energy. (See 'Deficit schizophrenia' above and
"Schizophrenia in adults: Clinical manifestations, course, assessment, and diagnosis", section on
'Deficit schizophrenia'.)
● Although the pathogenesis of the disorder is unknown, schizophrenia is likely a syndrome

comprised of multiple diseases that present with similar signs and symptoms. The disorder
appears to proceed from a complex interaction between genes and the environment. (See
'Pathogenesis' above.)
● Several neurotransmitter systems are involved in the pathology of schizophrenia including

dopamine, glutamate, GABA, and acetylcholine. These represent the current best targets for
pharmacological intervention in the disorder. (See 'Neurotransmitters' above and
"Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment".)
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Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis: A Randomized
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Topic 14804 Version 21.0

GRAPHICS
Some genes of interest in schizophrenia
Gene name or Hypothesized

Gene Notes
product function
Catechol-O-methyl COMT Catecholamine At position 158 in the resulting protein: a

transferase (including dopamine) VAL/VAL allele is more active than a VAL/MET
metabolism or MET/MET allele.
The VAL/VAL allele is associated with greater
risk of psychosis in cannabis users [1]. Position
22q11.
D-amino acid oxidase DAOA/G30 and DAO DAO breaks down D- DAOA/G30 and DAO are an interacting pair of
activator/D-amino serine, which is an genes [2].
acid oxidase NMDA receptor
cofactor
Disrupted in DISC1 Wide array of Discovered from studying a Scottish family

schizophrenia 1 hypothesized with many members having a severe mental
functions from cell disorder and also a translocation disrupting
migration during the expression of the gene. Position 1q42.
development to
dendritic outgrowths
and cell adhesion
Dystrobrevin binding DTNBP1 Axon stability Also associated with skeletal muscle. Position
protein 1 (dysbindin) 6p22.
Gamma-aminobutyric GABRB2 Inhibitory There is evidence of GABA signaling system

acid (GABA) A neurotransmission abnormalities in schizophrenia. Position 5q34.
receptor subunit beta
2
Neuregulin 1 NRG1 Signal transduction NRG1 undergoes alternative splicing into

related to cell growth several proteins. Position 8p12-21.
and differentiation
Zinc finger protein ZNF804A Unknown (may be Identified in GWAS study [3].
804A transcription factor) Also associated with bipolar disorders.
Examination of rare alleles of the gene found
no difference in rates in schizophrenia
compared to controls [4].
References:
1. Henquet C, Rosa A, Krabbendam L, et al. An experimental study of catechol-O-methyltransferase Val158Met
moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology
2006; 31:2748.
2. Corvin A, McGhee KA, Murphy K, et al. Evidence for association and epistasis at the DAOA/G30 and D-amino acid
oxidase loci in an Irish schizophrenia sample. Am J Med Genet B Neuropsychiatr Genet 2007; 144B:949.
3. O'Donovan MC, Craddock N, Norton N, et al. Identification of loci associated with schizophrenia by genome-wide
association and follow-up. Nat Genet 2008; 4:1053.
4. Dwyer S, Williams H, Holmans P, et al. No evidence that rare coding variants in ZNF804A confer risk of schizophrenia.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 2010; 153B:1411.
Graphic 69865 Version 3.0

Contributor Disclosures
Bernard A Fischer, MD Nothing to disclose Robert W Buchanan, MD Nothing to disclose Stephen Marder,
MD Grant/Research/Clinical Trial Support: Takeda [Schizophrenia]; Boeringer Ingleheim
[Psychosis/Schizophrenia]. Consultant/Advisory Boards: Boeringer-Ingleheim, Otsuka; Allergan; Roche; Teva
[Schizophrenia (brexpiprazole, cariprazine)]; Lundbeck [Psychosis/schizophrenia (Long-acting aripiprazole)];
Bioexcel [Psychosis/schizophrenia]; Sunovion [Psychosis/schizophrenia (Lurasidone)]. Richard Hermann,
MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

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Official reprint from UpToDate®

Schizophrenia in adults: Epidemiology and pathogenesis

Characteristics of schizophrenia typically include positive symptoms, such as hallucinations or

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● Depressive disorders (see "Depression in schizophrenia")

● Living in an urban area [8,9]

● Obstetrical complications [12]

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Deficit schizophrenia — Deficit schizophrenia, characterized by primary, enduring negative

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Environmental risk factors

Obstetrical complications — Various perinatal problems, grouped together for analysis as

● Numerous epidemiological studies have found an increase in schizophrenia prevalence in

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• Bacterial infections during childhood, which lead to hospitalization, are related to an

● Acquired hemolytic anemia

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In contrast to the psychotomimetic properties of delta-9-tetrahydrocannabinol, the cannabis ingredient

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Immigration — Numerous studies in multiple countries have observed a higher prevalence of

● Schizophrenia may be overdiagnosed in immigrant populations; however, further research

• Ethiopian immigrants to Israel [84]

● The increased risk of schizophrenia in immigrants may be related to vitamin D deficiency,

Glutamate — Glutamate is the major CNS excitatory neurotransmitter. Hypofunction of the N-

● Challenge studies using ketamine (a NMDA receptor antagonist) [90-92]

● Genetic findings [89]

● Post-mortem studies [93]

Gamma-amino-butyric acid — Gamma-amino-butyric acid (GABA) is the major CNS inhibitory

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SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

● Approximately 15 to 20 percent of patients with schizophrenia have the deficit form of

● Although the pathogenesis of the disorder is unknown, schizophrenia is likely a syndrome

● Several neurotransmitter systems are involved in the pathology of schizophrenia including

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3. McGrath J, Saha S, Chant D, Welham J. Schizophrenia: a concise overview of incidence,

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8. Krabbendam L, van Os J. Schizophrenia and urbanicity: a major environmental influence--

9. Pedersen CB, Mortensen PB. Evidence of a dose-response relationship between urbanicity

16. Somaiya M, Grover S, Avasthi A, Chakrabarti S. Changes in cost of treating schizophrenia:

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46. Myhrman A, Rantakallio P, Isohanni M, et al. Unwantedness of a pregnancy and schizophrenia

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71. Andréasson S, Allebeck P, Engström A, Rydberg U. Cannabis and schizophrenia. A longitudinal

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77. D'Souza DC, Abi-Saab WM, Madonick S, et al. Delta-9-tetrahydrocannabinol effects in

80. Bhattacharyya S, Wilson R, Appiah-Kusi E, et al. Effect of Cannabidiol on Medial Temporal,

84. Youngmann R, Pugachova I, Zilber N. Patterns of psychiatric hospitalization among ethiopian

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94. Schwarcz R, Rassoulpour A, Wu HQ, et al. Increased cortical kynurenate content in

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Topic 14804 Version 21.0

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Some genes of interest in schizophrenia

Gene name or Hypothesized

Catechol-O-methyl COMT Catecholamine At position 158 in the resulting protein: a

Disrupted in DISC1 Wide array of Discovered from studying a Scottish family

Gamma-aminobutyric GABRB2 Inhibitory There is evidence of GABA signaling system

Neuregulin 1 NRG1 Signal transduction NRG1 undergoes alternative splicing into