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Gene-environment interactions in severe mental illness.

Rudolf Uher1

  • 1Department of Psychiatry, Dalhousie University , Halifax, NS , Canada ; Department of Psychology and Neuroscience, Dalhousie University , Halifax, NS , Canada ; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London , London , UK.

Frontiers in Psychiatry
|May 27, 2014
PubMed
Summary

Gene-environment interactions are crucial for severe mental illnesses (SMI), influencing genetic predisposition and environmental exposures. Understanding these links helps explain SMI development and guides future research strategies.

Keywords:
bipolar disordergene–environment interactionsgenome-wide association studiesmajor depressive disorderschizophreniasevere mental illness

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Area of Science:

  • Psychiatry
  • Genetics
  • Environmental Health

Background:

  • Severe mental illnesses (SMI), including schizophrenia, bipolar disorder, and depression, arise from complex interactions between genetic predisposition and environmental factors.
  • Evidence suggests a significant interplay between genetic and environmental influences, impacting heritability estimates and disorder development.
  • The vulnerability of offspring from parents with SMI to environmental exposures highlights the conditional expression of genetic liability.

Purpose of the Study:

  • To explore the role of gene-environment interactions (GxE) in the etiology of severe mental illnesses.
  • To review identified GxE findings and discuss their implications for understanding SMI.
  • To propose strategies for future genome-wide investigations of GxE in SMI.

Main Methods:

  • Review of existing literature on gene-environment interactions in severe mental illnesses.
  • Identification of specific gene polymorphisms and environmental factors implicated in SMI development.
  • Analysis of findings related to psychosis, persistent depressive disorder, and bipolar disorder.

Main Results:

  • Replicated findings include AKT1 gene polymorphism and cannabis use interaction in psychosis, and serotonin transporter gene interaction with childhood maltreatment in depression.
  • A study identified a BDNF gene polymorphism interaction with stressful life events in triggering bipolar depressive episodes.
  • A systematic search revealed a CTNNA3 polymorphism sensitizing the brain to in utero cytomegalovirus, potentially leading to schizophrenia.

Conclusions:

  • Gene-environment interactions are fundamental to the development of severe mental illnesses.
  • Future research requires integrated epidemiological and genetic approaches, comprehensive environmental assessments, and prioritized genetic variant analysis.
  • Understanding GxE is critical for advancing the diagnosis, prevention, and treatment of SMI.