Gene-environment Interaction in Psychosis

Just as psychotic disorders, their symptoms,course, and treatment response vary between individuals, they differ across places and demographic groups too. 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.

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, 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.

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.

Gene-environment interaction approach is particularly suitable 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 this approach, research is focussing on subclinical symptoms that can be traced to prior persistence of clinically relevant symptoms.

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According to the model of psychosis proneness - persistence - impairment, genetic background factors impact on a broadly distributed and transitory population expression of psychosis during development. Hence, poor prognosis, in terms of persistence and clinical need, can be predicted by environmental exposure interacting with genetic risk.

According to findings from epidemiological research, the following environmental risk factors have significant impact on children and adolescents growing up in European societies.

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1. Urbanicity: For children growing up in big cities a more than twofold risk compared to children in rural environments has been shown, independent of other risk factors.

2. Migration: Migration presents an increasing challenge to European countries. In immigrant populations the risk of developing psychotic disorders is much higher compared to the risk in both the host country and the country of origin.

3. Cannabis use: Although its effects were considered to be harmless compared to other drugs until recently, many studies have shown that cannabis use, in particular heavy use during adolescence, increases the risk of psychotic disorders such as schizophrenia.

4. Childhood victimisation: The study pointing to a link between childhood trauma and psychotic disorders is remarkably consistent in showing strong effects on disease vulnerability.

Now for the first time in the European Union a rational strategy of focused research collaboration has been devised with a unique, large-scale project, which aims to unravel the causes of schizophrenia and related psychotic disorders.

This multidisciplinary project is designed to focus on the effects of gene-environment interactions on brain pathways and psychological vulnerability, and to elucidate how subtle, but measurable, behavioural expressions of vulnerability for psychotic disorder are mediated by cerebral and psychological pathways.

The current model of gene-environment interaction is nurturing promising approaches to understand the symptoms of schizophrenia and related psychotic disorders and improve treatment.

Source-ANI