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Risk and Resilience: Animal Models Shed Light on the Pivotal Role of Inflammation in Individual Differences in Stress-Induced Depression

  • Jennifer C. Felger
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia

    Winship Cancer Institute, Emory University, Atlanta, Georgia
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  • Ebrahim Haroon
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia
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  • Andrew H. Miller
    Correspondence
    Address correspondence to Andrew H. Miller, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1365-B Clifton Road, 5th Floor, B 5101, Atlanta, GA 30322
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia

    Winship Cancer Institute, Emory University, Atlanta, Georgia
    Search for articles by this author
      Data indicate a compelling relationship between inflammation and depression that may have profound clinical relevance (
      • Haroon E.
      • Raison C.L.
      • Miller A.H.
      Psychoneuroimmunology meets neuropsychopharmacology: Translational implications of the impact of inflammation on behavior.
      ). A significant proportion of patients with depression reliably exhibit increased inflammatory markers, and exposure of humans to stress, a well-known precipitant of depression, is associated with activation of inflammatory responses. Nevertheless, an important unresolved question is whether inflammation is a cause or a consequence of depression. For example, if inflammation causes depression, strategies to reduce inflammation would be a rational approach to reduce the risk of the disease and ultimately to treat it. Alternatively, if increased inflammation is a consequence of the many biologic alterations that occur as a result of stress or depression including changes in the regulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, both of which have potent immunomodulatory effects, increased inflammation in depression, while representing a significant deleterious repercussion of the disorder, may have limited relevance to its pathogenesis. Thus, teasing apart this issue of cause or consequence becomes essential for understanding the relative strategy for addressing inflammation and determining its relevance to the risk for depression and other stress-related disorders.
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