Anxiety, depression and substance abuse are among the most common types of psychopathology that have their onset during adolescence. Anxious temperament identified during childhood is a significant risk factor for the later development of these illnesses. Since mechanistic and controlled stress exposure experiments cannot be performed in children, the proposed studies will use an extensively validated non human primate model with state of the art functional imaging and molecular methods to understand the neural circuits and molecular mechanisms underlying the adolescent vulnerability to develop stress-induced psychopathology. An important component of these studies is that they will, in young non human primates, use methods of assessment similar to those in the human studies, including functional and structural imaging, to prospectively study the interaction between increased childhood amygdala reactivity and the development of stress-induced psychopathology during adolescence. Importantly, brain tissue will be collected to assess the extent to which dysregulated amygdala corticotropin releasing factor systems underlie the adolescent vulnerability to develop anxiety and depression. It is expected that these studies will find that: 1) increased amygdala reactivity in childhood is associated with anxious temperament and predicts later risk, 2) maladaptive responses to stress that are associated with adolescent psychopathology involve failure of adaptive prefrontal-amygdala interactions, and 3) increased amygdala CRF activity underlies the vulnerability to develop stress-induced psychopathology.
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