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Emotion and Development Branch

Section on Bipolar Spectrum Disorders (SBSD)

BSD focuses on two severe pediatric mood disorders with significant public health impact: bipolar disorder (BD) and chronic, severe irritability. Our studies of irritability include both youth with the DSM-5 diagnosis of Disruptive Mood Dysregulation Disorder (DMDD) and those whose irritability is more mild but still impairing. Our work consists of studies on the brain mechanisms underlying BD and irritability, and on testing novel treatments for DMDD. We conduct pathophysiological research, based on systems neuroscience principles and techniques, with the goal of informing novel treatment development.

We focus on pediatric BD because it is associated with severe impairment, both cross-sectionally and over time. Our focus on irritability arose in response to questions about whether severely impairing irritability, without distinct manic episodes, should be considered to be a form of pediatric BD. To facilitate research on this question, we defined a syndrome called severe mood dysregulation (SMD); this research informed the DSM-5 discussions regarding DMDD. Our brain-based research, in concert with longitudinal and family studies, support the conclusion that, while both BD and chronic irritability are very impairing in youth, they are not manifestations of the same illness. That is, relatively few youth with severe irritability develop BD in adulthood. This conclusion has significant treatment implications.

Bipolar disorder is a relatively rare, highly heritable illness with a distinct clinical presentation i.e., the manic episode. Thus, our BD research focuses on identifying BD-specific biological risk factors or risk markers present in youth and adults with BD, and in unaffected youth at risk for BD. A relatively distinctive feature of our work is the comparison of BD youth, not only to healthy volunteers, but also to youth with severe irritability or other illnesses, adults with BD, and unaffected youth at risk for BD. Our specific focus, motivated by consistent behavioral deficits we identified and by the literature, is on identifying BD-specific neural dysfunction that affects face emotion processing.

Compared to BD, clinically significant irritability is more common and less heritable, and its clinical presentation varies with development. Unlike BD, chronic irritability is a stable trait with a range of severity in the population. Chronic irritability is also present in youth with a number of psychiatric diagnoses e.g., anxiety, ADHD. Thus, although our initial work on childhood irritability focused only on SMD, our work now treats irritability as a dimensional trait and explores neural correlates across the range of severity and in the context of a number of childhood diagnoses. This work links experimentally-induced frustration to behavioral and systems neuroscientific correlates of irritability. Our treatment studies, which focus on DMDD, test treatments distinct from those for BD and apply our brain-based findings to the development of novel treatments.