Journal
HARVARD REVIEW OF PSYCHIATRY
Volume 19, Issue 3, Pages 109-124Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.3109/10673229.2011.586551
Keywords
antidepressant medication; childhood maltreatment; cognitive-behavioral therapy; depression; epigenetics; gene-environment interactions; personalized medicine; pharmacogenetics; stressful life events
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Funding
- Medical Research Council [G9817803B] Funding Source: researchfish
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A principal weakness of evidence-based psychiatry is that it does not account for the individual variability in therapeutic response among individuals with the same diagnosis. The aim of personalized psychiatry is to remediate this shortcoming and to use predictors to select treatment that is most likely to be beneficial for an individual. This article reviews the evidence that genetic variation, environmental exposures, and gene-environment interactions shapemental illness and influence treatment outcomes, with a primary focus on depression. Several genetic polymorphisms have been identified that influence the outcome of specific treatments, but the strength and generalizability of such influences are not sufficient to justify personalized prescribing. Environmental exposures in early life, such as childhood maltreatment, exert long-lasting influences that are moderated by inherited genetic variation and mediated through stable epigenetic mechanisms such as tissue-and gene-specific DNA methylation. Pharmacological and psychological treatments act on and against the background of genetic disposition, with epigenetic annotation resulting from previous experiences. Research in animal models suggests the possibility that epigenetic interventions may modify the impact of environmental stressors on mental health. Gaps in evidence are identified that need to be bridged before knowledge about cause can inform cure in personalized psychiatry. (HARV REV PSYCHIATRY 2011;19:109-124.)
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