Department of Anthropology, Emory University, United States; Department of Psychiatry and Behavioral Sciences, Emory University, United States; Center for Behavioral Neuroscience, Emory University, United States; Yerkes National Primate Research Center, Emory University, United States; Center for Translational Social Neuroscience, Emory University, United States.
Department of Psychology, University of Kansas, United States.
Psychoneuroendocrinology. 2014 Jan;39:237-248. doi: 10.1016/j.psyneuen.2013.09.022. Epub 2013 Sep 27.
Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary pre-clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner's Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses of males more similar to responses of females in the placebo group and vice versa, raising the prospect of an inverted u-shaped dose response to central OT levels. These findings emphasize the need to fully characterize the effects of intranasal OT and AVP in both males and females and at multiple doses before widespread clinical application will be warranted.
催产素（OT）和血管加压素（AVP）都已知可以调节社会行为，并且人们推测这两个系统的功能障碍可能是某些涉及社会行为缺陷的精神疾病的潜在原因。特别是，人们对鼻内 OT 作为某些精神疾病的潜在治疗方法越来越感兴趣，初步的临床前和临床研究表明，它可以缓解一些相关症状。然而，这些研究中的绝大多数研究参与者都是男性，并且有证据表明，神经肽在人类和非人类动物中存在性别差异的影响。迄今为止，没有研究调查鼻内 OT 对同一范式中男性和女性大脑功能的影响。此前，在一项随机、安慰剂对照、双盲 fMRI 研究中，我们报告了鼻内 OT 和 AVP 对男性人类在玩一种称为囚徒困境游戏的互动社交游戏时的行为和大脑活动的影响。在这里，我们呈现了一项在女性人类中进行的相同研究的结果，并将这些结果与我们从男性中得到的结果进行了比较。总的来说，我们发现鼻内 OT 和 AVP 的行为和神经反应都具有高度的性别差异。在女性中，AVP 增加了和解行为，OT 和 AVP 都使女性对电脑伙伴的态度更像人类。在男性中，AVP 增加了来自人类和电脑伙伴的合作互惠。然而，男性和女性之间没有共享特定的药物对行为的影响。在合作互动中，OT 和 AVP 都增加了男性大脑中富含 OT 和 AVP 受体的区域以及在奖励、社交联系、唤醒和记忆中发挥关键作用的区域（例如，纹状体、基底前脑、脑岛、杏仁核和海马体）的大脑活动，而 OT 和 AVP 要么没有影响，要么在某些情况下实际上减少了女性这些区域的大脑活动。OT 治疗使男性的神经反应更类似于安慰剂组中女性的反应，反之亦然，这表明对中枢 OT 水平的反应呈倒 U 形剂量依赖性。这些发现强调了在广泛的临床应用之前，需要充分描述鼻内 OT 和 AVP 在男性和女性中的作用，以及在多个剂量下的作用。
