This study has two specific aims: 1) to use longitudinal, objective techniques to characterize the clinical manifestations of early-onset bipolar disorder (BPD); and 2) to identify neurophysiological correlates of affective dysregulation in bipolar children and adolescents. To accomplish Specific Aim #1, we will obtain prospective clinical data (including daily mood and behavioral ratings and actigraphy data) and direct observational data, and perform neuropsychological assessments. To accomplish Specific Aim #2, we will use standardized emotional stimuli to test the hypothesis that responses to negative emotional stimuli are more pronounced in children with BPD than in controls. In addition, we will assess the psychiatric status of family members, bank genetic samples from patients and first-degree relatives for use in future studies, and follow the patients longitudinally (clinically and with structural MRI scans) for 4 years. One hundred children have been screened for inclusion in the study, and twenty have been accepted. While all of the screened patients are receiving treatment in the community for BPD, only those who meet strict DSM-IV criteria for the illness, including episodicity(i.e. the """"""""narrow phenotype""""""""), are accepted into the study. Comparison of the """"""""accepted"""""""" and """"""""ruled-out"""""""" groups indicate that the accepted patients are more likely to have a parental history of BPD; lifetime history of suicide attempts and psychosis; and to exhibit hallmark symptoms of mania (e.g. elation, grandiosity, decreased need for sleep, increased goal-directed activity). Actigraphy and daily mood rating data from children accepted into the study and their parents indicate that parent report of behaviors consistent with a manic day is associated with increased motor activity. Preliminary neuropsychological data indicate possible memory deficits, including verbal memory (consistent with reports in adult BPD), visual spatial memory, and working memory. Finally, behavioral data indicate that, compared to control subjects, bipolar children are delayed on motor inhibition tasks, and were prone to misidentify faces (especially those of peers) as angry.
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