Sippel Lauren M, Allington Casey E, Pietrzak Robert H, Harpaz-Rotem Ilan, Mayes Linda C, Olff Miranda
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.
Chronic Stress (Thousand Oaks). 2017 Feb;1. doi: 10.1177/2470547016687996. Epub 2017 Feb 17.
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.
需要有新型药物疗法来改善患有应激相关精神障碍个体的治疗效果。神经激素催产素(OT)因其对社会情感脑的影响而成为一个有前景的候选药物。在本综述中,我们概述了支持OT用于治疗重度抑郁症和创伤后应激障碍的证据。我们首先讨论内源性OT,研究表明它尚未成为应激相关障碍的可靠生物标志物。其次,我们回顾鼻内(IN)OT对健康人群中与应激相关障碍相关过程(快感缺失、奖赏处理、心理社会应激反应性、恐惧/焦虑和社会行为)及其神经生物学机制(例如,突显网络和下丘脑 - 垂体 - 肾上腺轴)的影响。第三,我们展示来自临床人群的稀少但有前景的研究结果,随后讨论为最大化OT的治疗潜力而需考虑的关键调节变量(例如,患者性别和儿童期虐待)。我们还指出了现有研究的异质性结果和局限性,包括依赖于对精神健康样本的单剂量研究以及关于IN药物递送和给药方案有效性的未解决问题。非常需要进行包括女性以及潜在调节变量测量的严格多剂量研究,这将有助于我们理解OT在预防和治疗应激相关精神障碍方面的效用。