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

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.