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LB-102

Schizophrenia

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Product information and disease descriptionPlace of product in therapyDisease description

Definition and etiology

12 evidence topics · 15 sources

Definition: disorder of thought, perception, emotion, and social interaction

“Schizophrenia is a mental disorder characterized by disruptions in thought processes, perceptions, emotional responsiveness, and social interactions. Although the course of schizophrenia varies among individuals, schizophrenia is typically persistent and can be both severe and disabling.” (opens the source at this quote in a new tab)

“Schizophrenia is characterized by positive psychotic symptoms such as hallucinations, delusions, disorganized speech, and disorganized or catatonic behavior; negative symptoms such as reduced motivation and expressiveness; and cognitive impairments affecting executive function, memory, and mental processing speed.” (opens the source at this quote in a new tab)

Definition: ICD-11 description of schizophrenia (6A20)

“Schizophrenia is characterised by disturbances in multiple mental modalities, including thinking (e.g., delusions, disorganisation in the form of thought), perception (e.g., hallucinations), self-experience (e.g., the experience that one's feelings, impulses, thoughts, or behaviour are under the control of an external force), cognition (e.g., impaired attention, verbal memory, and social cognition), volition (e.g., loss of motivation), affect (e.g., blunted emotional expression), and behaviour (e.g., behaviour that appears bizarre or purposeless, unpredictable or inappropriate emotional responses that interfere with the organisation of behaviour).” (opens the source at this quote in a new tab)

“Persistent delusions, persistent hallucinations, thought disorder, and experiences of influence, passivity, or control are considered core symptoms. Symptoms must have persisted for at least one month in order for a diagnosis of schizophrenia to be assigned.” (opens the source at this quote in a new tab)

Etiology: interaction of genetic and environmental risk factors

“Multifaceted interactions between genetic and environmental risk factors give rise to schizophrenia. These risk factors also affect early brain development and shape the biological response to life experiences, thereby influencing the onset and progression of the disorder.” (opens the source at this quote in a new tab)

“Thus, schizophrenia is a polygenic disorder resulting from the combined effects of multiple genes spread across the genome, each contributing modestly.” (opens the source at this quote in a new tab)

Heritability: twin studies

“The probandwise concordance rate of SZ is 33% in monozygotic twins and 7% in dizygotic twins. We estimated the heritability of SZ to be 79%. When expanding illness outcome to include SZ spectrum disorders, the heritability estimate was almost similar (73%).” (opens the source at this quote in a new tab)

“By using a multigroup twin model, we found evidence for substantial additive genetic effects-the point estimate of heritability in liability to schizophrenia was 81% (95% confidence interval, 73%-90%). Notably, there was consistent evidence across these studies for common or shared environmental influences on liability to schizophrenia-joint estimate, 11% (95% confidence interval, 3%-19%).” (opens the source at this quote in a new tab)

Common genetic variants: genome-wide association study of 76,755 people with schizophrenia

“Schizophrenia has a heritability of 60–80%, much of which is attributable to common risk alleles. Here, in a 2-stage genome-wide association study of up to 76,755 people with schizophrenia and 243,649 controls, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes expressed in CNS neurons, excitatory and inhibitory, but not other tissues or cell types.” (opens the source at this quote in a new tab)

Rare variants: 22q11.2 deletion

“While linked common genetic variants have less impact on risk, rare mutations have a more significant impact.” (opens the source at this quote in a new tab)

“One such rare mutation is the chromosome 22q11.2 deletion, which increases lifetime risk 25-fold.” (opens the source at this quote in a new tab)

Environmental risk factors: cannabis use

“A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers.” (opens the source at this quote in a new tab)

“Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3·2, 95% CI 2·2–4·1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4·8, 2·5–6·3).” (opens the source at this quote in a new tab)

Environmental risk factors: obstetric and perinatal complications

“The meta-analytic synthesis of the prospective population-based studies revealed that three groups of complications were significantly associated with schizophrenia: 1) complications of pregnancy (bleeding, diabetes, rhesus incompatibility, preeclampsia); 2) abnormal fetal growth and development: (low birthweight, congenital malformations, reduced head circumference), and 3) complications of delivery (uterine atony, asphyxia, emergency Cesarean section). Pooled estimates of effect sizes were generally less than 2.” (opens the source at this quote in a new tab)

“152 studies relating to 98 risk or protective factors were eligible for analysis.” (opens the source at this quote in a new tab)

“any maternal (OR 4·60) or paternal (OR 2·73) psychopathology; maternal psychosis (OR 7·61) and affective disorder (OR 2·26)” (opens the source at this quote in a new tab)

“hypoxia (OR 1·63); ruptured (OR 1·86) and premature rupture (OR 2·29) of membranes; polyhydramnios (OR 3·05); definite obstetric complications NOS (OR 1·83); birthweights of less than 2000 g (OR 1·84), less than 2500 g (OR 1·53), or 2500-2999 g (OR 1·23)” (opens the source at this quote in a new tab)

Environmental risk factors: urbanicity

“The risk for schizophrenia at the most urban environment was estimated to be 2.37 times higher than in the most rural environment. The same effect was found when studies measuring the risk for nonaffective psychosis were included.” (opens the source at this quote in a new tab)

Environmental risk factors: migration

“The mean weighted relative risk for developing schizophrenia among first-generation migrants (40 effect sizes) was 2.7 (95% confidence interval [CI]=2.3-3.2). A separate analysis performed for second-generation migrants (seven effect sizes) yielded a relative risk of 4.5 (95% CI=1.5-13.1).” (opens the source at this quote in a new tab)

“The meta-analysis yielded a RR, adjusted for age and sex, of 2.13 (95% CI 1.99–2.27) for NAPD and 2.94 (95% CI 2.28–3.79) for APD. The RRs diminished, but persisted after adjustment for SES.” (opens the source at this quote in a new tab)

Environmental risk factors: childhood adversity

“There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34–3.31).” (opens the source at this quote in a new tab)

Risk and protective factors: umbrella review of 170 putative factors

“Fifty‐five meta‐analyses or systematic reviews were included in the umbrella review, corresponding to 683 individual studies and 170 putative risk or protective factors for psychotic disorders. Only the ultra‐high‐risk state for psychosis (odds ratio, OR=9.32, 95% CI: 4.91‐17.72) and Black‐Caribbean ethnicity in England (OR=4.87, 95% CI: 3.96‐6.00) showed convincing evidence of association.” (opens the source at this quote in a new tab)