Anxiety, depression and substance abuse are among the most common types of psychopathology that havetheir onset during adolescence. Anxious temperament identified during childhood is a significant risk factorfor the later development of these illnesses. Since mechanistic and controlled stress exposure experimentscannot be performed in children, the proposed studies will use an extensively validated non human primatemodel with state of the art functional imaging and molecular methods to understand the neural circuits andmolecular 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 ofassessment similar to those in the human studies, including functional and structural imaging, toprospectively study the interaction between increased childhood amygdala reactivity and the development ofstress-induced psychopathology during adolescence. Importantly, brain tissue will be collected to assess theextent to which dysregulated amygdala corticotropin releasing factor systems underlie the adolescentvulnerability to develop anxiety and depression. It is expected that these studies will find that: 1) increasedamygdala 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 ofadaptive prefrontal-amygdala interactions, and 3) increased amygdala CRF activity underlies thevulnerability to develop stress-induced psychopathology.
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