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 and neuropsychological correlates of affective dysregulation in bipolar children and adolescents. A particular focus of aim #2 is the identification of behavioral paradigms that assess psychological processes that are important in the pathophysiology of BPD, and that can be used either in subsequent fMRI studies (to identify dysfunctional neural circuitry in patients) or in family studies (to identify behavioral and biological markers of the illness i.e. endophenotypes). Approximately 26 patients and matched controls have been assessed on a battery of such paradigms. The data indicate that , compared to controls, children with BPD have deficits in 1)memory, including verbal memory (consistent with reports in adult BPD) and visual spatial memory; 2) their ability to adapt their behavior in response to changing rewards and punishments (i.e. response reversal); 3) their ability to inhibit a dominant motor response and initiate another; and 4) the ability to identify facial emotions in other children (but not adults). The latter deficit differentiates them from children with ADHD or other mood and anxiety disorders. In addition, we have developed a behavioral test in the laboratory to demonstrate that, in the context of frustration, children with BPD adopt a more impulsive response style. In addition to obtaining and analyzing these behavioral data, this year an fMRI study was begun using the motor inhibition paradigm. Finally, we continue to assess the psychiatric status of family members, bank genetic samples from patients and parents for use in future studies, and follow the patients longitudinally (clinically and with structural MRI scans) for 4 years.
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