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.

Adolescent mental illness is a tremendous public health concern because it affects roughly half of American adolescents and accounts for nearly 9 billion dollars in mental-health expenses annually. Clinical research with adolescent samples highlights the importance of trust and attachment security in the parent-child relationship as essential components of adolescent well-being. Oxytocin has recently emerged as a biological correlate of trust and attachment security and, as result, widespread speculation has pointed to its potential role as a clinical intervention. The proposed research seeks to explore the effect of oxytocin on adolescents' trust game behavior towards their mothers and the moderating effect of attachment security. As the first study to explore the effect of oxytocin on trust in adolescent, this study will lay the groundwork for better understanding the neurobiology of trust and attachment in this age group and will inform future research evaluating the clinical value of oxytocin by determining for whom this therapy may be beneficial. By exploring key social (attachment), behavioral (trust game), and biological (oxytocin) processes in both inpatient adolescents and healthy controls, this project has direct relevance for the mission of the NIMH to support multi-faceted research exploring mental illness and reflects the aim of the NICHD to emphasize the social context of adolescent mental health.