Bipolar disorder (BPD) is one of the most virulent, costly, and debilitating psychiatric disorders. The offspring of parents with BPD have been found in childhood to be at increased risk for a broad range of behavioral and mood disorders and associated impairment, which represent highly morbid outcomes in their own right and which may predispose to later BPD. The temperamental trait """"""""Behavioral Disinhibition"""""""" (BD), reflecting the extreme tendency to seek out novelty, approach unfamiliar stimuli, and display disinhibition of speech and action, may be an early indicator of the behavioral and affective dysregulation that characterizes offspring at risk for BPD. BD is measurable through direct laboratory observations in children as young as toddlers and preschoolers, earlier than mood disorders can be reliably diagnosed. We therefore propose a longitudinal study of laboratory-observed BD and its symptomatic, neurocognitive, and psychosocial outcomes in 100 young (2-5-year-old) offspring of parents with Bipolar I Disorder and 100 comparison offspring of parents without mood disorders. Based on our prior findings, we hypothesize that BD will predict subsequent mood and disruptive behavior disorders and associated impairment in high-risk offspring. We also hypothesize that rates of BD will be significantly elevated among high-risk offspring compared with control offspring. Additionally, this study will enable us to explore the interactions of BD with familial and environmental risk and protective factors in the expression of psychopathology in offspring. It will also enable us to explore longitudinal associations between BD and other constructs thought to contribute to psychopathology in children (e.g. effortful control of behavior/ impulses), to explore subtle differences between alternate neurobiological models of BD, and to examine whether BD represents an endophenotype of bipolar disorder. Ascertainment of this valuable, well-characterized sample will pave the way for follow-up studies exploring the genetic and functional neurologic bases of BD, disruptive behavior disorders and bipolar disorder, and our research group has a proven record of success at progressing from studies carefully characterizing early phenotypes of offspring at risk to neuroimaging, genetic, and early intervention studies. The ability to identify very early in life the individuals at highest risk for these adverse outcomes, and for BPD itself, is of the highest clinical and public health importance, since it will help us understand how these disorders develop, facilitate early detection of this disorder, and enable the development of preventive interventions.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Psychosocial Development, Risk and Prevention Study Section (PDRP)
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Avenevoli, Shelli A
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Massachusetts General Hospital
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Chai, Xiaoqian J; Hirshfeld-Becker, Dina; Biederman, Joseph et al. (2016) Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression. Biol Psychiatry 80:849-858
Chai, Xiaoqian J; Hirshfeld-Becker, Dina; Biederman, Joseph et al. (2015) Functional and structural brain correlates of risk for major depression in children with familial depression. Neuroimage Clin 8:398-407