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Gene–environment interplay in the etiology of psychosis

Published online by Cambridge University Press:  15 January 2018

Alyson Zwicker ,
Eileen M. Denovan-Wright  and
Rudolf Uher
Alyson Zwicker
Affiliation:
Department of Pathology, Dalhousie University, Halifax, NS, Canada Department of Psychiatry, Dalhousie University, Halifax, NS, Canada Nova Scotia Health Authority, Halifax, NS, Canada
Eileen M. Denovan-Wright
Affiliation:
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada
Rudolf Uher*
Affiliation:
Department of Pathology, Dalhousie University, Halifax, NS, Canada Department of Psychiatry, Dalhousie University, Halifax, NS, Canada Nova Scotia Health Authority, Halifax, NS, Canada Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK
*
Author for correspondence: Rudolf Uher, E-mail: uher@dal.ca
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Abstract

Schizophrenia and other types of psychosis incur suffering, high health care costs and loss of human potential, due to the combination of early onset and poor response to treatment. Our ability to prevent or cure psychosis depends on knowledge of causal mechanisms. Molecular genetic studies show that thousands of common and rare variants contribute to the genetic risk for psychosis. Epidemiological studies have identified many environmental factors associated with increased risk of psychosis. However, no single genetic or environmental factor is sufficient to cause psychosis on its own. The risk of developing psychosis increases with the accumulation of many genetic risk variants and exposures to multiple adverse environmental factors. Additionally, the impact of environmental exposures likely depends on genetic factors, through gene–environment interactions. Only a few specific gene–environment combinations that lead to increased risk of psychosis have been identified to date. An example of replicable gene–environment interaction is a common polymorphism in the AKT1 gene that makes its carriers sensitive to developing psychosis with regular cannabis use. A synthesis of results from twin studies, molecular genetics, and epidemiological research outlines the many genetic and environmental factors contributing to psychosis. The interplay between these factors needs to be considered to draw a complete picture of etiology. To reach a more complete explanation of psychosis that can inform preventive strategies, future research should focus on longitudinal assessments of multiple environmental exposures within large, genotyped cohorts beginning early in life.

Keywords

environmental risk factorsgene–environment interactionsgeneticspsychosisschizophrenia
Type
Invited Review
Information
Psychological Medicine , Volume 48 , Issue 12 , September 2018 , pp. 1925 - 1936
Copyright
Copyright © Cambridge University Press 2018 

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