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Review
. 2019 Dec;24(12):1770-1778.
doi: 10.1038/s41380-019-0457-6. Epub 2019 Jul 24.

Genomics and psychological resilience: a research agenda

Karmel W Choi  1   2   3   4 , Murray B Stein  5   6 , Erin C Dunn  7   8   9   10 , Karestan C Koenen  7   11   8   9 , Jordan W Smoller  7   11   8   9
Affiliations
Review

Genomics and psychological resilience: a research agenda

Karmel W Choi et al. Mol Psychiatry. 2019 Dec.

Abstract

Although exposure to adversity increases risk for poor mental health outcomes, many people exposed to adversity do not develop such outcomes. Psychological resilience, defined broadly as positive emotional and/or behavioral adaptation to adversity, may be influenced by genetic factors that have remained largely unexplored in the era of large-scale genome-wide studies. In this perspective, we provide an integrative framework for studying human genome-wide variation underlying resilience. We first outline three complementary working definitions of psychological resilience-as a capacity, process, and outcome. For each definition, we review emerging empirical evidence, including findings from positive psychology, to illustrate how a resilience-based framework can guide novel and fruitful directions for the field of psychiatric genomics, distinct from the ongoing study of psychiatric risk and related traits. Finally, we provide practical recommendations for future genomic research on resilience, highlighting a need to augment cross-sectional findings with prospective designs that include detailed measurement of adversities and outcomes. A research framework that explicitly addresses resilience could help us to probe biological mechanisms of stress adaptation, identify individuals who may benefit the most from prevention and early intervention, and ascertain modifiable protective factors that mitigate negative outcomes even for those at high genetic risk.

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Conflict of interest statement

Conflict of Interest Disclosures:

Dr Choi, Dr Dunn, and Dr Koenen have no conflicts of interest to disclose. Dr Stein has in the past 3 years been a consultant for Actelion, Aptinyx, Dart Neuroscience, Healthcare Management Technologies, Janssen, Neurocrine Biosciences, Oxeia Biopharmaceuticals, Pfizer, and Resilience Therapeutics. Dr Stein owns founders shares and stock options in Resilience Therapeutics and has stock options in Oxeia Biopharmaceticals. Dr Smoller is an unpaid member of the Bipolar/Depression Research Community Advisory Panel of 23andMe.

Figures

Figure 1.
Figure 1.
Proposed integrative genomic framework for resilience. GWAS = genome-wide association studies. MR = Mendelian randomization studies. GxE = gene-by-environment studies.
Figure 2.
Figure 2.
Novel features of a resilience framework for psychiatric genomics.
See this image and copyright information in PMC

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