Oxytocin and Social Engagement

描述(申请人提供)：现有的对动物和人类成年人的研究表明，催产素是一种很有前途的治疗工具，因为它增加了对社会关系的信任和依恋--这是一系列精神障碍的关键因素。催产素已被推荐作为青少年精神病理学的治疗方法，在青少年中，治疗提供者对其他药物选择持谨慎态度。然而，这一建议在很大程度上仍然是没有根据的，之前只有一项研究对患有精神病态的青少年使用催产素。在此背景下，本申请的目的是(A)在一个旨在评估活体内可量化的社会行为的游戏中，检查鼻腔内给药催产素对母亲信任行为的影响，确定这种影响在住院青少年和健康对照青少年中的差异，以及(B)探索基线依恋安全作为每个组内的调节因素，以确定影响是否取决于现有的社会关系。第二个目标是首次探索精神病理学与催产素对信任的影响之间的关系。中心假设是，催产素将增加整个样本中的信任行为，并通过提高住院患者样本中的信任水平来展示临床潜力，使其更接近社区青少年的信任行为。在每一组中，催产素有望在更大程度上增加具有安全依恋风格的青少年的信任行为。该方法是招募100名住院青少年和100名健康对照，进行随机、双盲、安慰剂对照设计，让他们自行鼻内注射催产素或安慰剂，并通过互联网与他们的母亲玩信任游戏。在本项目完成后，预计将确定催产素对住院患者和健康对照组青少年父母信任行为的影响，以及依恋安全感的调节作用。此外，关于催产素效应和内化和外化症状之间关系的有价值的初步数据将被收集作为更细粒度分析的基础，将这一有希望的研究路线延续到博士后研究。这项研究的影响是向确定催产素是否以及对谁具有临床价值迈出了第一步，在青少年依恋和症状学关键变量的背景下，通过增加信任来确定催产素可能具有临床价值。除了强调NICHD对青少年精神健康的社会背景的重视外，这项建议还反映了NIMH的使命，通过与依恋和信任相关的神经生物学机制来寻求了解青少年精神疾病；使用新的实验任务；以及整合关于催产素对行为(信任)和经验(依恋)变量的影响的数据。此外，二次分析呼应了RDoC在维度上研究精神病理学的指控，跨越了诊断界限。最后，该奖项将有助于培训一名年轻的研究人员从事独立的研究事业。

DESCRIPTION (provided by applicant): Existing research with animals and human adults suggests that oxytocin is a promising therapeutic tool because it increases trust and attachment in social relationships-key factors in a range of psychiatric disorders. Oxytocin has been recommended as a treatment for psychopathology in adolescents, a population in which treatment providers are wary of other pharmacological options. However, this suggestion remains largely unfounded, with only one previous study administering oxytocin to adolescents with psychopathology. Against this background, the objectives of the current application are to (a) examine the effect of intranasal oxytocin administration on trust behavior towards mothers in a game designed to assess in vivo, quantifiable social behavior, determining how this effect differs among inpatient and healthy control adolescents and (b) explore baseline attachment security as a moderator within each group to determine whether the effect differs depending upon the existing social relationship. A secondary aim is to explore, for the first time, how dimensionally rated psychopathology relates to the effect of oxytocin on trust. The central hypothesis is that oxytocin will increase trust behavior in the whole sample, and demonstrate clinical potential by raising the level of trust in the inpatient sample nearer to the trust behavir of community adolescents. Within each group, oxytocin is expected to increase trust behavior to a greater degree among adolescents with a secure attachment style. The approach is to recruit 100 inpatient adolescents and 100 healthy controls for a randomized, double blind, placebo-controlled design in which they self- administer intranasal oxytocin or a placebo and play a trust game with their mother over the internet. At the completion of this project, it is the expectation that the effect of oxytocin on adolescent-parent trust behavior among inpatients and healthy controls and the moderating role of attachment security will be determined. Moreover, valuable pilot data regarding the relation between oxytocin effects and internalizing and externalizing symptoms will be collected as the basis of more fine-grained analyses, continuing this promising line of research to post-doctoral study. The impact of this study is taking a first step towards determining whether, and for whom, oxytocin may have clinical value by increasing trust, within the context of the critical variables of attachment and symptomatology in adolescents. In addition to addressing the NICHD emphasis on the social context of adolescent mental health, this proposal reflects the mission of the NIMH by seeking to understand adolescent mental illness via the neurobiological mechanisms associated with attachment and trust; using a novel experimental task; and integrating data on the effect of oxytocin on behavioral (trust) and experiential (attachment) variables. Moreover, secondary analyses echo RDoC's charge to study psychopathology dimensionally, cutting across diagnostic boundaries. Finally, this award will aid in the training of a young researcher for an independent research career.