Social and spatial heterogeneity in psychosis proneness in a multilevel case-prodrome-control study.

OBJECTIVE: To test whether spatial and social neighbourhood patterning of people at ultra-high risk (UHR) of psychosis differs from first-episode psychosis (FEP) participants or controls and to determine whether exposure to different social environments is evident before disorder onset. METHOD: We tested differences in the spatial distributions of representative samples of FEP, UHR and control participants and fitted two-level multinomial logistic regression models, adjusted for individual-level covariates, to examine group differences in neighbourhood-level characteristics. RESULTS: The spatial distribution of controls (n = 41) differed from UHR (n = 48; P = 0.04) and FEP participants (n = 159; P = 0.01), whose distribution was similar (P = 0.17). Risk in FEP and UHR groups was associated with the same neighbourhood-level exposures: proportion of single-parent households [FEP adjusted odds ratio (aOR): 1.56 95% CI: 1.00-2.45; UHR aOR: 1.59; 95% CI: 0.99-2.57], ethnic diversity (FEP aOR: 1.27; 95% CI: 1.02-1.58; UHR aOR: 1.28; 95% CI: 1.00-1.63) and multiple deprivation (FEP aOR: 0.88; 95% CI: 0.78-1.00; UHR aOR: 0.86; 95% CI: 0.76-0.99). CONCLUSION: Similar neighbourhood-level exposures predicted UHR and FEP risk, whose residential patterning was closer to each other's than controls. Adverse social environments are associated with psychosis before FEP onset.

Clinical and sociodemographic comparison of people at high-risk for psychosis and with first-episode psychosis.

OBJECTIVE: To compare clinical and sociodemographic characteristics previously associated with psychosis, between individuals at high-risk for psychosis (HR) and patients experiencing a first episode psychosis (FEP), to achieve a better understanding of factors associated with psychosis. METHOD: Cross-sectional comparison of 30 individuals at HR with 30 age-gender matched FEP, presenting to an early intervention service for psychosis. Participants were followed-up for 2 years to establish the proportion of HR who made the transition into FEP. RESULTS: Both groups showed similar socio-clinical characteristics, including immigration status, employment history, marital status, family history of psychotic illness, self-harm and alcohol and drug use. The HR group had a lower level of education, higher burden of trauma, earlier onset of psychiatric symptoms and a longer delay in accessing specialised services. A younger onset of symptoms was associated with a longer delay in accessing services in both groups. After a 2 year follow-up, only three (10%) of the HR group made a transition into FEP. CONCLUSION: The similarities observed between individuals at HR and those with FEP suggest that known variables associated with psychosis may be equally prevalent in people at HR who do not develop a psychotic disorder.

Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies.

BACKGROUND: Disruption of foetal development by prenatal maternal infection is consistent with a neurodevelopmental model of schizophrenia. Whether specific prenatal infections are involved, their timing and the mechanisms of any effect are all unknown. We addressed these questions through a systematic review of population-based studies. METHOD: Electronic and manual searches and rigorous quality assessment yielded 21 studies that included an objective assessment of individual-level prenatal maternal infection and standardized psychotic diagnoses in adult offspring. Methodological differences between studies necessitated a descriptive review. RESULTS: Results for prenatal maternal non-specific bacterial, respiratory or genital and reproductive infection differed between studies, which reported up to a two- to fivefold increased risk of schizophrenia. Evidence for herpes simplex virus type 2 (HSV-2) and Toxoplasma gondii was mixed; some studies reported up to a doubling of schizophrenia risk. Prenatal HSV-1 or cytomegalovirus (CMV) infections were not associated with increased risk. Exposure to influenza or other infections during early pregnancy may be more harmful than later exposure. Increased proinflammatory cytokines during pregnancy were also associated with risk. Prenatal infection was associated with structural and functional brain abnormalities relevant to schizophrenia. CONCLUSIONS: Prenatal exposure to a range of infections and inflammatory responses may be associated with risk of adult schizophrenia. Larger samples, mediation and animal models should be used to investigate whether there is a 'sensitive period' during development, and the effects of prenatal infections on neurodevelopment. Inclusion of genetic and immunological information should help to elucidate to what extent genetic vulnerability to schizophrenia may be explained by vulnerability to infection.