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The Neurobiology of Resilience: Complexity and Hope

  • James W. Murrough
    Correspondence
    Address correspondence to James W. Murrough, M.D., Ph.D., Icahn School of Medicine at Mount Sinai, Psychiatry, 1 Gustave L. Levy Place, Box 1230, New York, NY 10029.
    Affiliations
    Depression and Anxiety Center for Discovery and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Affective Neuroscience Center, Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Scott J. Russo
    Affiliations
    Depression and Anxiety Center for Discovery and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York

    Affective Neuroscience Center, Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York
    Search for articles by this author
      The societal burden of stress-related neuropsychiatric disorders is staggering. Major mental health sequelae of maladaptive responses to stress in humans include major depressive disorder and posttraumatic stress disorder (PTSD), although the risk of developing nearly every psychiatric condition is increased as a result of stress exposure (
      • Herane V.A.
      • De Angel V.
      • Papadopoulos A.
      • Strawbridge R.
      • Wise T.
      • Young A.H.
      • et al.
      The relationship between cortisol, stress and psychiatric illness: New insights using hair analysis.
      ). A driving hope for this field is that new insights into the mechanisms of stress resilience will lead to novel therapeutic discoveries. Over the past decade it has become increasingly apparent that the tendency to resist development of negative psychiatric consequences following extreme or prolonged stress is in fact a highly adaptive process. From this perspective, the most salient features of resilience in the face of stress likely reflect active regulation of key neurobehavioral systems aimed at the maintenance of homeostasis, rather than simply the absence of stress-related maladaptive changes (
      • Russo S.J.
      • Murrough J.W.
      • Han M.H.
      • Charney D.S.
      • Nestler E.J.
      Neurobiology of resilience.
      ). Moreover, individual differences in coping strategies mediated by sex and developmental factors play crucial roles in resilience (
      • Wood S.K.
      • Bhatnagar S.
      Resilience to the effects of social stress: Evidence from clinical and preclinical studies on the role of coping strategies.
      ). The neurobiological mechanisms of stress resilience are exceedingly complex. Detailed investigations of resilience mechanisms have implicated alterations in specific neurocircuits, epigenetic mechanisms, immune pathways, and microbiota-related pathways. Such studies are beginning to illuminate some consistent themes but in many cases are yielding more questions than answers. Perhaps this is to be expected given the nature of the topic, the inherent complexity of brain-behavior relationships, and the relative youth of the field. Still, patients are waiting for new treatments and the field is growing impatient. When will basic insights into the mechanisms of resilience yield therapeutic results for patients suffering from disorders such as major depressive disorder or PTSD? Or better yet, when will we be able to prevent the onset of these disabling disorders? In this special issue of Biological Psychiatry, the selected articles from basic, clinical, and translational perspectives address the topic of neurobiology of resilience; together these articles summarize the essential components of our knowledgebase concerning this important and rapidly expanding topic.
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