Pediatric bipolar disorder (PBD) is increasingly recognized, poorly understood, and ineffectively treated. With newly available fMRI technology, the field has matured for use in children to examine underlying brain dysfunction and treatment effects in PBD. There are very few investigators in the field trained to integrate clinical trials with fMRI methods. This career (K23) award will permit the candidate to develop as an independent clinical investigator to fill this void. The project described below serves as a medium to learn new skills under the mentorship of active, senior clinical investigators and will also allow her to take part in didactic training by protecting her time for these activities. The proposal reflects the need to bring a multidisciplinary approach to clinical research, particularly in the area of pediatric psychiatric research. Thus, the plan emphasizes pharmacotherapy, clinical trial methodology, statistics, ethics, and brain imaging using fMRI. The plan includes regular supervision by her primary mentors, interactions with internal and external-consultants and attendance at relevant didactic courses. Drs. Janicak and Sweeney will be the primary mentors. The study described in this application will examine treatment effects on the disturbances of affective circuitry hypothesized to underlie PBD. Specifically, the central aim is to conduct a double-blind, randomized clinical trial to test the hypothesis that the novel antipsychotic, risperidone, will have a rapid onset of action and efficacy at least comparable to divalproex sodium in the treatment of mixed and manic episodes of PBD. A pilot study, using a subset of subjects, will investigate whether activity in the amygdala and prefrontal cortex (PFC) underlies dysfunction in the affective circuitry of PBD and whether effective treatment normalizes any aberrant activity. During five years, 40 outpatient subjects with PBD manic or mixed episodes, ages 8-17 years, referred to the UI Pediatric Mood Disorder Clinic will be recruited.
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