This project comprises two longitudinal twin studies that integrate the study of affective style, affective symptomatology, and affect-related physiology in children and adolescents. In Study A, the twins have already been followed longitudinally with a variety of measures, including detailed videotaped observations. An additional follow-up at age 11-12 years will allow developmental characterization of affective style and frank anxiety/depression. The genetic bases of improvement; chronic course; onset of comorbid symptoms, and other developmental variables will be pursued, as will the link between behavior and some of the neuroscience variables examined by other Center projects. Study A will also seek to identify toddler age risk factors (e.g., shy/inhibited temperament, obsessive features and repetitive movements, auditory and tactile sensitivities, and difficulties in down-regulating negative affect) that might be associated with later internalizing behavioral patterns. Study A shares an assessment protocol with Project 5 (Essex/Klein). To examine the impact of non-genetic factors (and other issues), genetically identical (MZ) cotwins from Study A who are discordant for chronic anxiety, as well as controls, will participate in structural neuroimaging studies. Core C will perform whole brain tensor-based morphometry, which should be more sensitive than most prior methods in determining whether regions of the hippocampus, prefrontal cortex, and amygdala are structurally altered in affected individuals and in their non-affected cotwins. Study B examines the association of individual differences in emotional reactivity and regulation with several psychophysiological measures (EEG, fear-potentiated startle, sympathetic and parasympathetic cardiac measures) as well as basal and reactive cortisol, all within a behavior-genetic framework. One role of Project 4's twin methodology in the broader Center is to help resolve the issue of causal direction in studies of experience and context in affective development. Another role is to determine whether physiological substrates of fearfulness/anxiety actually have a genetic basis, and whether common genetic variance accounts for affect-physiology associations.