FRONTO-LIMBIC BRAIN OF BIPOLAR CHILDREN AND ADOLESCENTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: Abnormalities in fronto-limbic brain (FLB) regions involved in mood regulations have been associated with bipolar disorder (BD) in neuroimaging studies on adults. Did these FLB abnormalities develop as BD progressed? Or, did they precede it, or emerge early during illness development? The latter would suggest that developmental abnormalities in brain maturational processes lead to FLB changes. If so, then treatments that reduce or alleviate these brain abnormalities early in the disease process might reduce the severity of BD. To test these hypotheses, we will conduct a combined in vivo neuroimaging and clinical intervention trial in adolescents who have BD (BD adolescents). We will examine the relationships between (a) FLB abnormalities, (b) BD symptoms, and (c) response to a mood stabilizing medication (valproate). RESEARCH PLAN: We will enroll 60 untreated (off psychotropic medications for at least two weeks) post-pubertal BD adolescents (ages 12-17 years old) who have been diagnosed, according to DSM-IV, with type I BD, and 60 healthy controls. Thirty of the BD subjects will not have any axis I psychiatric co-morbidities, while another 30 will have co-morbid attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), and/or conduct disorder (CD). METHODS: Each subject will undergo a brain magnetic resonance imaging and spectroscopy (MRI/MRS) scan and neuropsychological testing. BD adolescents will receive treatment with valproate monotherapy for a period of 6 weeks, which will be followed by a second MRI/MRS scan. CLINICAL RELEVANCE: Very few MRI studies have focused on investigating brain abnormalities possibly involved in pathophysiology of BD in childhood and adolescence. Considering the evidence for detectable FLB abnormalities in key brain regions involved in mood regulations in adult BD cases reviewed below and the preliminary data in BD adolescents, there is an important need for additional in vivo imaging studies that would examine the involvement of FLB circuits in pathophysiology of early-onset BD and treatment response.