Meyer-Lindenberg Andreas
Central Institute of Mental Health, Mannheim, Germany.
Prog Brain Res. 2008;170:463-70. doi: 10.1016/S0079-6123(08)00436-6.
Oxytocin and vasopressin are key effectors of social behaviour (Insel, T. R. and Fernald, R. D. (2004). Annu. Rev. Neurosci., 27: 697-722). Oxytocin effects in humans were recently demonstrated by a behavioural study showing selectively increased trust after hormone administration (Kosfeld, M., et al. (2005). Nature, 435: 673-676). Since this suggested involvement of the amygdala, which is linked to trust (Winston, J. S., et al. (2002). Nat. Neurosci., 5: 277-283) - presumably because of its role in danger monitoring - and highly expresses oxytocin receptors (Huber, D., et al. (2005). Science, 308: 245-248), we studied amygdala circuitry after double-blind crossover intranasal application of placebo or oxytocin (Kirsch, P., et al. (2005). J. Neurosci., 25: 11489-11493). Oxytocin potently reduced amygdala activation and decreased coupling to brainstem regions implicated in autonomic and behavioural manifestations of fear, indicating a neural mechanism for the effects of oxytocin in social cognition in humans and providing a potential therapeutic approach to social anxiety currently being tested in social phobia and autism. Furthermore, these data suggested a translational genetic approach. Preliminary findings (data not presented) from our laboratory using imaging genetics indeed implicate genetic variants for both AVPR1A, encoding the primary receptor of vasopressin in brain, and the oxytocin receptor, OXTR, in amygdala regulation and activation. Taken together, our results indicate neural mechanisms for human social behaviour mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder and in social dysfunction in general.
催产素和加压素是社会行为的关键效应分子（英塞尔，T.R.和费尔纳德，R.D.（2004年）。《神经科学年度评论》，27卷：697 - 722页）。最近一项行为研究证明了催产素对人类的影响，该研究表明激素给药后信任选择性增加（科斯费尔德，M.等人（2005年）。《自然》，435卷：673 - 676页）。由于这表明杏仁核参与其中，杏仁核与信任相关（温斯顿，J.S.等人（2002年）。《自然神经科学》，5卷：277 - 283页）——大概是因为其在危险监测中的作用——并且高度表达催产素受体（胡贝尔，D.等人（2005年）。《科学》，308卷：245 - 248页），我们在双盲交叉鼻内应用安慰剂或催产素后研究了杏仁核回路（基尔希，P.等人（2005年）。《神经科学杂志》，25卷：11489 - 11493页）。催产素有力地降低了杏仁核的激活，并减少了与参与恐惧的自主和行为表现的脑干区域的耦合，这表明了催产素在人类社会认知中发挥作用的神经机制，并为目前正在社交恐惧症和自闭症中测试的社交焦虑提供了一种潜在的治疗方法。此外，这些数据提示了一种转化遗传学方法。我们实验室使用成像遗传学的初步发现（未展示数据）确实表明，编码大脑中加压素主要受体的AVPR1A基因变体以及杏仁核调节和激活中的催产素受体OXTR基因变体都有牵连。综上所述，我们的结果表明了人类社会行为的神经机制，通过对杏仁核信号传导的影响介导自闭症的遗传风险，并为探索针对该疾病及一般社交功能障碍中异常杏仁核功能的治疗策略提供了理论依据。
