The present proposal builds on our 12-year longitudinal study of children and families and our history of collaboration with Davidson, Goldsmith and Kalin. Through the Wisconsin Study of Families and Work we have followed families from before birth to late childhood (Grade 5) and have tracked children's individual differences in affective style, most notably repeated observations of emotional reactivity and regulation and sampling of salivary cortisol at age 4 1/2 and Grades 3 and 5. The main context for the planned studies is our recent finding that children with the highest basal cortisol levels at age 41/2 had been exposed to greater stress (especially maternal depression) both in infancy and in the preschool period when cortisol was sampled, and further that the cortisol predicted psychiatric symptoms in Kindergarten and Grades 1, 3, and 5. Consistent with preclinical animal studies and other human studies, our findings suggest that early stress may sensitize children's HPA systems and emotional responses to be more vulnerable to later stress. We will follow the children through Grade 9 to further investigate consequences of prior and ongoing stress exposure and emotional reactivity for psychiatric symptoms/disorders, cognitive functioning, brain morphometry, and the brain circuitry involved in emotion regulation. The collaboration and research resources afforded by a Center structure allow us to integrate state-of-the- art imaging and hormonal assessments with longitudinal measures of behavioral, emotional, cognitive, and social functioning. Major aims are 1) to investigate associations of children's longitudinal patterns of basal cortisol with their history of stress exposure, emotional reactivity and regulation, cognitive functioning, and course of internalizing problems; 2) to investigate individual differences in morphometric variation (with a focus on PFC, amygdala, hippocampus) of early adolescents' brains, and associations with longitudinal patterns of stress exposure, basal cortisol, emotional reactivity and regulation, and cognitive functioning; and 3) to use functional imaging to assess individual differences in responsivity of key structures associated with emotion and emotion regulation as they relate to the behavioral phenotype, internalizing. These studies provide an unprecedented opportunity to integrate behavioral and neuroscience approaches to begin to elucidate key mechanisms involved in the mental health problems of children/adolescents.