DESCRIPTION (provided by applicant): The overall objective of this project is to explore the biological bases of individual variation in cooperative social behavior among normal subjects, with the goal of developing hypotheses to explain more extreme variation that manifests as mental illness. Cooperative behavior will be measured in an interactive social task known as the Prisoner's Dilemma (PD) Game. There are four specific aims. Aim 1 is to examine the relationship between individual variation in cooperative behavior and individual variation in brain function during the PD game. This will be accomplished by imaging subjects' brains with fMRI as they play an iterated Prisoner's Dilemma Game with each of two assumed human partners. These data will allow us to evaluate an existing model of the neural systems that facilitate and inhibit cooperation. Aim 2 is to examine the relationship between individual variation in cooperative behavior and individual variation in prefrontal cortex anatomy. This aim will involve acquiring a structural MRI scan from each subject to measure morphometric variation, as well as a diffusion tensor imaging (DTI) brain scan to measure white matter integrity. Aim 3 is to investigate the impact of intranasal oxytocin and vasopressin, neuropeptides associated with social bonding, on cooperative behavior and associated brain activity. In this placebo-controlled, double-blind experiment, subjects will be randomized to one of three conditions: intranasal oxytocin administration, intranasal vasopressin administration, or intranasal placebo administration. Functional brain activity and behavior will be compared across treatment groups. Aim 4 is to examine the relationship between individual variation in cooperative behavior and individual genetic variation. Saliva samples will be collected from each subject for analysis of genes hypothesized to have an influence on cooperative social behavior. Ultimately, these data will identify factors that contribute to trust and its reciprocation which are essential components of cooperative social behavior. Trust and its reciprocation are essential components of healthy interpersonal relationships, as evidenced by several psychiatric disorders in which they are lacking, including autism, depression, psychopathic personality disorder and several axis II personality disorders. By identifying factors that influence cooperative behavior in a normal population, this project will generate hypotheses as to the causes of more severe variation associated with mental illness.

Relevance: Trust and its reciprocation are essential components of healthy interpersonal relationships, as evidenced by several psychiatric disorders in which they are lacking, including autism, depression, psychopathic personality disorder and several axis II personality disorders. By identifying factors that influence cooperative behavior in a normal population, this project will generate hypotheses as to the causes of more severe variation associated with mental illness.