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Genomics and psychological resilience: a research agenda

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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Acknowledgements

We would like to thank Kristen Nishimi, MPH, and Christy Denckla, PhD, for formative discussions and ongoing collaborations on resilience. Dr Choi was supported in part by a National Institute of Mental Health (NIMH) grant T32MH017119. Dr Smoller is a Tepper Family Massachusetts General Hospital Research Scholar and supported in part by the Demarest Lloyd, Jr. Foundation and NIMH grant K24MH094614. Dr Dunn was supported by a National Institute of Mental Health grant R01MH113930. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to Karmel W. Choi.

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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.

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Choi, K.W., Stein, M.B., Dunn, E.C. et al. Genomics and psychological resilience: a research agenda. Mol Psychiatry 24, 1770–1778 (2019). https://doi.org/10.1038/s41380-019-0457-6

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