Given mounting evidence for prepubertal-specific manifestations of DSM- IV mania, establishing continuities/discontinuities of bipolarity (BP) across the lifespan is crucial. Because family studies are paramount among validating methodologies, the paucity of family study data from prepubertal BP probands is striking. An especially compelling opportunity to fill this gap in family study knowledge exists in our research unit because of ongoing phenomenologic, naturalistic course, and molecular genetic investigations. These ongoing studies are conducted on a population of 270 non-adopted probands aged 7-16 years old at baseline entry into the phenomenology project. These 270 subjects comprise 90 with BP (with or without ADHD), 90 with ADHD (without BP or other major mood disorders), and 90 community controls (without BP, other major mood disorders or ADHD) who were ascertained to optimize future family genetic studies. Thus, the family study proposed in this application will use an already established pediatric aged proband population and will include probands' first degree relatives, who already participate in molecular genetic investigations. In the proposed work, first degree relatives (mothers, fathers and siblings aged seven or older) will be directly assessed by blind raters to establish DSM-IV diagnoses. Data on deceased or otherwise unavailable relatives will be obtained by family history from two informants, to increase caseness. Incorporation of the proposed family study with ongoing interrelated and interlocking phenomenology, naturalistic course, and molecular-genetic investigations will provide crucial data on differentiating prepubertal BP from ADHD and on establishing continuities/discontinuities between prepubertal versus adult onset mania. This application is a second revision to NIMH R01 MH57451.
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