A systematic review of all reported incidence and prevalence studies of population rates of subclinical psychotic experiences reveals a median prevalence rate of around 5% and a median incidence rate of around 3%. A meta-analysis of risk factors reveals associations with developmental stage, child and adult social adversity, psychoactive drug use, and also male sex and migrant status. The small difference between prevalence and incidence rates, together with data from follow-up studies, indicates that approximately 75-90% of developmental psychotic experiences are transitory and disappear over time. There is evidence, however, that transitory developmental expression of psychosis (psychosis proneness) may become abnormally persistent (persistence) and subsequently clinically relevant (impairment), depending on the degree of environmental risk the person is additionally exposed to. The psychosis proneness-persistence-impairment model considers genetic background factors impacting on a broadly distributed and transitory population expression of psychosis during development, poor prognosis of which, in terms of persistence and clinical need, is predicted by environmental exposure interacting with genetic risk.

The current systematic review and meta-analysis provides an extended and comprehensive overview of the associations between neurocognitive and social cognitive functioning and different types of functional outcome. Literature searches were conducted in MEDLINE and PsycINFO and reference lists from identified articles to retrieve relevant studies on cross-sectional associations between neurocognition, social cognition and functional outcome in individuals with non-affective psychosis. Of 285 studies identified, 52 studies comprising 2692 subjects met all inclusion criteria. Pearson correlations between cognition and outcome, demographic data, sample sizes and potential moderator variables were extracted. Forty-eight independent meta-analyses, on associations between 12 a priori identified neurocognitive and social cognitive domains and 4 domains of functional outcome yielded a number of 25 significant mean correlations. Overall, social cognition was more strongly associated with community functioning than neurocognition, with the strongest associations being between theory of mind and functional outcomes. However, as three-quarters of variance in outcome were left unexplained, cognitive remediation approaches need to be combined with therapies targeting other factors impacting on outcome.

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17–29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn’s disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10−11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10−9), ANK3 (rs10994359, P = 2.5 × 10−8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10−9).