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Chronic Stress (Thousand Oaks). 2017 Feb;1. doi: 10.1177/2470547017694461. Epub 2017 Apr 10.

Early Life Stress, Mood, and Anxiety Disorders.

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Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.


Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health's proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.


child abuse and neglect; early life stress; epigenetics; hypothalamic pituitary axis; research domain criteria

Conflict of interest statement

Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Charles B. Nemeroff, MD, PhD, Research/ Grants: National Institutes of Health (NIH). Consulting (last three years): Xhale, Takeda, Mitsubishi Tanabe Pharma Development America, Taisho Pharmaceutical Inc., Lundbeck, Prismic Pharmaceuticals, Bracket (Clintara), Total Pain Solutions (TPS), Gerson Lehrman Group (GLG) Healthcare & Biomedical Council, Fortress Biotech, Sunovion Pharmaceuticals Inc., Sumitomo Dainippon Pharma, Janssen Research & Development, LLC, Magstim, Inc.; Stockholder: Xhale, Celgene, Seattle Genetics, Abbvie, OPKO Health, Inc., Bracket Intermediate Holding Corp., Network Life Sciences Inc.; Scientific Advisory Boards: American Foundation for Suicide Prevention (AFSP), Brain and Behavior Research Foundation (BBRF) (formerly named National Alliance for Research on Schizophrenia and Depression [NARSAD]), Xhale, Anxiety Disorders Association of America (ADAA), Skyland Trail, Bracket (Clintara), RiverMend Health LLC, Laureate Institute for Brain Research, Inc.; Board of Directors: AFSP, Gratitude America, ADAA; Income sources or equity of US$10,000 or more: American Psychiatric Publishing, Xhale, Bracket (Clintara), CME Outfitters, Takeda; Patents: Method and devices for transdermal delivery of lithium (US 6,375,990B1) and method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2).

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