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Chronic Stress (Thousand Oaks). 2017 Feb;1. doi: 10.1177/2470547016687996. Epub 2017 Feb 17.

Oxytocin and Stress-related Disorders: Neurobiological Mechanisms and Treatment Opportunities.

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U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Veterans Affairs Connecticut Health Care System, West Haven, CT, USA.
Yale Child Study Center, New Haven, CT, USA.
Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
Arq Psychotrauma Expert Group, Diemen, The Netherlands.


Novel pharmacotherapies that improve outcomes for individuals with stress-related psychiatric disorders are needed. The neurohormone oxytocin (OT) is a promising candidate given its influence on the social-emotional brain. In this review, we present an overview of evidence supporting OT's utility for treating major depressive disorder and posttraumatic stress disorder. We first discuss endogenous OT, which research suggests is not yet a reliable biomarker of stress-related disorders. Second, we review effects of intranasal (IN) OT on processes relevant to stress-related disorders in healthy populations (anhedonia, reward processing, psychosocial stress reactivity, fear/anxiety, and social behavior) and their neurobiological mechanisms (e.g., the salience network and hypothalamic-pituitary-adrenal axis). Third, we present the sparse but promising findings from clinical populations, followed by discussion of critical moderating variables to consider in the service of maximizing the therapeutic potential of OT (e.g., patient sex and child maltreatment). We also identify heterogeneous findings and limitations of existing research, including reliance on single-dose studies in psychiatrically healthy samples and unanswered questions regarding the effectiveness of IN drug delivery and dosing schedules. Well-controlled multidose studies including women and measures of potentially moderating variables are sorely needed and would inform our understanding of the utility of OT for preventing and treating stress-related psychiatric disorders.


Intranasal oxytocin; anxiety; context; fear; major depressive disorder; pharmacology; posttraumatic stress disorder; psychotherapy; reward; sex


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: Dr Pietrzak has received travel funds from Johnson & Johnson for work that is unrelated to this project.

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