Urban locales, other environmental factors, influence risk

The incidence of psychotic disorders varies greatly across places and demographic groups, as do symptoms, course, and treatment response across individuals. High rates of schizophrenia in large cities, and among immigrants, cannabis users, and traumatised individuals reflect the causal influence of environmental exposures. This, in combination with progress in the area of molecular genetics, has generated interest in more complicated models of schizophrenia aetiology that explicitly posit gene-environment interactions.Unravelling the causes of psychotic disorders Schizophrenia and related psychotic disorders have a complex aetiology. Research has attempted to determine the role of specific biological variables, such as genetic and biochemical factors and subtle changes in brain morphology. Genetic vulnerability in schizophrenia is shared in part with bipolar disorder and recent molecular genetic findings also indicate an overlap with developmental disorders such as autism (Van Os & Kapur, 2009). According to twin and family studies more than half of the vulnerability for schizophrenia is of genetic origin. However, attempts to discover genes that relate directly to psychotic disorder have been frustrating and often disappointing, and despite enormous investments, the identification of actual molecular genetic variants underlying schizophrenia liability has proven extremely difficult. This difficulty is mainly due to the phenomenon of gene-environment interaction, which is defined as genetic control of sensitivity to the environment. Exciting findings in other areas of psychiatry have motivated researchers to turn their attention to better understanding the complex ways in which genetic factors interact with non-genetic factors to produce psychosis. Biological vulnerability factors with a genetic background interact with complex physical, psychological and environmental vulnerability factors. Conceptualised in a model, gene-environment interaction proposes that genes influencing risk for schizophrenia may not do so directly (the dominant model until recently), but indirectly by making individuals more sensitive to the effects of causal environmental risk factors. The 'genotype x environmental interaction' approach differs from the linear gene-phenotype approach by positing a causal role not for either genes or environment in isolation but for their synergistic co-participation in the cause of psychosis where the effect of one is conditional on the other (Van Os et al., 2008). Gene-environment interaction seems a particularly suitable approach for understanding the development of psychosis because this phenotype is known to be associated with environmentally mediated risks, yet people display considerable heterogeneity in their response to those environmental exposures. In the framework of gene-environment interaction, research is focussing on subclinical symptoms that can be traced to prior persistence of clinically relevant symptoms. For example, in a substantial proportion of patients with bipolar disorder, onset of illness may be seen as the poor outcome of a developmentally common and usually transitory non-clinical bipolar phenotype (Tijssen et al., 2010). In schizophrenia and related psychotic disorders, the median prevalence of subclinical psychotic experiences is reported to be around 5% and the median incidence rate to be around 3%. The difference between prevalence and incidence rates, together with data from follow-up studies, indicates that approximately 75