Kendrick Keith M, Guastella Adam J, Becker Benjamin
Key Laboratory for Neuroinformation, School of Life Science and Technology, Center for Information in Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Brain and Mind Center, University of Sydney, Sydney, NSW, Australia.
Curr Top Behav Neurosci. 2018;35:321-348. doi: 10.1007/7854_2017_19.
Social dysfunction is a core symptom of many psychiatric disorders and current medications have little or no remedial effects on this. Following on from extensive studies on animal models demonstrating that the neuropeptide oxytocin plays an important role in social recognition and bonding, human-based research has explored its therapeutic potential for social dysfunction in psychiatric disorders. Here we outline the historical background of this human-based research and some of the current methodological challenges it is facing. To date, research has primarily attempted to establish functional effects through measuring altered endogenous concentrations, observing effects of exogenous administration and by investigating the effects of polymorphisms and epigenetic modifications of the oxytocin receptor gene. We summarize some of the key findings on behavioral and neural effects that have been reported in healthy subjects in the context of social cognition which have provided encouragement that oxytocin could represent a promising therapeutic target. At the same time, we have identified a number of key areas where we urgently need further information about optimal dosing strategies and interactions with other peptide and transmitter systems. Finally, we have summarized current translational findings, particularly in the context of therapeutic outcomes of intranasal oxytocin administration in autism and schizophrenia. These clinical findings while somewhat varied in outcome do offer increasing cause for optimism that targeting the oxytocin system may provide a successful therapeutic approach for social dysfunction. However, future research needs to focus on the most effective treatment strategy and which types of individuals are likely to benefit most.
社会功能障碍是许多精神疾病的核心症状,而目前的药物对此几乎没有或根本没有治疗效果。在对动物模型进行广泛研究表明神经肽催产素在社会认知和联系中起重要作用之后,基于人类的研究探索了其对精神疾病中社会功能障碍的治疗潜力。在此,我们概述了这项基于人类研究的历史背景以及它目前面临的一些方法学挑战。迄今为止,研究主要试图通过测量内源性浓度的变化、观察外源性给药的效果以及研究催产素受体基因的多态性和表观遗传修饰的影响来确定功能效应。我们总结了在社会认知背景下健康受试者中报告的一些关于行为和神经效应的关键发现,这些发现为催产素可能成为一个有前景的治疗靶点提供了鼓舞。同时,我们确定了一些关键领域,在这些领域我们迫切需要更多关于最佳给药策略以及与其他肽和递质系统相互作用的信息。最后,我们总结了当前的转化研究结果,特别是在自闭症和精神分裂症中鼻内给予催产素的治疗结果方面。这些临床结果虽然在结果上有些不同,但确实越来越让人乐观地认为,针对催产素系统可能为社会功能障碍提供一种成功的治疗方法。然而,未来的研究需要关注最有效的治疗策略以及哪些类型的个体可能受益最大。