ReviewNeurobiology of Resilience: Interface Between Mind and Body
Section snippets
Stress, Resilience, and the Hypothalamic-Pituitary-Adrenal Axis
An adequate reaction of the body to acute threats is a crucial mechanism to adapt to environmental changes that occur in different developmental stages throughout life. The autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis play a key role in orchestrating the body’s reaction to threats (2). Upon danger, the hypothalamus secretes corticotropin-releasing hormone, which via the pituitary hormone adrenocorticotropin induces the production of cortisol from the adrenal
Rodent Models of Susceptibility and Resilience
The neurobiological mechanisms underlying resilience have long been difficult to uncover, primarily because creating significant adversity in humans in controlled experimental settings is impossible and because the exploration of molecular and circuit brain mechanisms in humans remains limited. Over the past decade, advances in preclinical animal stress models that uncover individual differences in stress reactivity have allowed detailed neurobiological characterization of the precise
Hippocampal Neurogenesis
The hippocampus is important in mediating responses to stress. Both mineralocorticoid and glucocorticoid receptors are vastly expressed in the hippocampus, making it a region that is highly responsive to activation of the HPA axis 40, 41. The dentate gyrus of the hippocampus is capable of generating functional neurons from adult neural precursors, a process called adult neurogenesis (42). Stress and glucocorticoid release decrease adult hippocampal neurogenesis, a process that is reversed by
The Innate Immune System
Both preclinical animal models and human studies show that repeated psychosocial stress leads to profound peripheral immunological changes 98, 99. Evidence from human studies linking stress vulnerability and resilience to immune alterations exists at multiple levels: a subset of patients with MDD show elevated levels of several proinflammatory cytokines 100, 101, MDD has high comorbidity with chronic inflammatory illnesses such as autoimmune disorders, cardiovascular disorders, or cancer 102,
Conclusions
The societal and individual burden entailed by stress-related neuropsychiatric disorders is immense. Efforts in developing treatments for such disorders have focused on preventing or reversing the damaging effects of stress. Understanding the neurobiological mechanisms that promote resilience to stress in some individuals, but lacking in those who are inherently more susceptible, constitutes a novel, additional important approach in stress biology. Indeed, early clinical studies suggest that
Acknowledgments and Disclosures
This work was supported by National Institute of Mental Health Grant Nos. R01 MH090264, P50 MH096890, and R01 MH104559 (to SJR), R56 MH115409 (to M-HH), and P50 MH096890 (to EJN), National Center for Complementary and Integrative Health Grant No. P50 AT008661-01 (to SJR), and an Early Postdoc Mobility Fellowship of the Swiss National Science Foundation and a Walter and Gertrud Siegenthaler Postdoctoral Fellowship (to FC).
SJR has provided consultation services to Danone and Sunovion
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