Resilience and the brain: a key role for regulatory circuits linked to social stress and support


Given the high prevalence and burden of mental disorders, fostering the understanding of protective factors is an urgent issue for translational medicine in psychiatry. The concept of resilience describes individual and environmental protective factors against the backdrop of established adversities linked to mental illness. There is convergent evidence for a crucial role of direct as well as indirect adversity impacting the developing brain, with persisting effects until adulthood. Direct adversity may include childhood maltreatment and family adversity, while indirect social adversity can include factors such as urban living or ethnic minority status. Recently, research has begun to examine protective factors which may be able to buffer against or even reverse these influences. First evidence indicates that supportive social environments as well as trait-like individual protective characteristics might impact on similar neural substrates, thus strengthening the capacity to actively cope with stress exposure in order to counteract the detrimental effects evoked by social adversity. Here, we provide an overview of the current literature investigating the neural mechanisms of resilience with a putative social background, including studies on individual traits and genetic variation linked to resilience. We argue that the regulatory perigenual anterior cingulate cortex and limbic regions, including the amygdala and the ventral striatum, play a key role as crucial convergence sites of protective factors. Further, we discuss possible prevention and early intervention approaches targeting both the individual and the social environment to reduce the risk of psychiatric disorders and foster resilience.

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The authors gratefully acknowledge grant support from the German Research Foundation (grant numbers DFG HO 5674/2-1, GRK2350/1) and the Olympia Morata Program of the University of Heidelberg to NEH. AML acknowledges grant support by the German Research Foundation (DFG, Research Training Group GRK2350/1 project B02, Collaborative Research Center SFB 1158 project B09, Collaborative Research Center TRR 265 project S02, grant ME 1591/4-1), German Federal Ministry of Education and Research (BMBF, grants 01EF1803A, 01ZX1314G, 01GQ1003B), European Union’s Seventh Framework Programme (FP7, grants 602450, 602805, 115300, HEALTH-F2-2010-241909), Innovative Medicines Initiative Joint Undertaking (IMI, grant 115008) and Ministry of Science, Research and the Arts of the State of Baden-Wuerttemberg, Germany (MWK, grant 42-04HV.MED(16)/16/1). HT acknowledges grant support by the DFG (Research Training Group GRK2350/1 project B02, Collaborative Research Center SFB 1158 project B04, Collaborative Research Center TRR 265 project A04) and BMBF (grants 01EF1803A project WP3, 01GQ1102). The funding source had no role in the writing of the report and in the decision to submit the article for publication.

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Correspondence to Andreas Meyer-Lindenberg.

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Conflict of interest

AML has received consultant fees from American Association for the Advancement of Science, Atheneum Partners, Blueprint Partnership, Boehringer Ingelheim, Daimler und Benz Stiftung, Elsevier, F. Hoffmann-La Roche, ICARE Schizophrenia, K. G. Jebsen Foundation, L.E.K Consulting, Lundbeck International Foundation (LINF), R. Adamczak, Roche Pharma, Science Foundation, Sumitomo Dainippon Pharma, Synapsis Foundation—Alzheimer Research Switzerland, System Analytics, and has received lectures fees including travel fees from Boehringer Ingelheim, Fama Public Relations, Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Janssen-Cilag, Klinikum Christophsbad, Göppingen, Lilly Deutschland, Luzerner Psychiatrie, LVR Klinikum Düsseldorf, LWL Psychiatrie Verbund Westfalen-Lippe, Otsuka Pharmaceuticals, Reunions i Ciencia S. L., Spanish Society of Psychiatry, Südwestrundfunk Fernsehen, Stern TV, and Vitos Klinikum Kurhessen. The other authors declare that they have no conflict of interest.

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Holz, N.E., Tost, H. & Meyer-Lindenberg, A. Resilience and the brain: a key role for regulatory circuits linked to social stress and support. Mol Psychiatry 25, 379–396 (2020).

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