Neural recruitment during failed motor inhibition differentiates youths with bipolar disorder and severe mood dysregulation

► Tested motor inhibition in youths with BD or SMD. ► BD exhibited reduced activation in several regions versus SMD and healthy children. ► Neural activation differed between two phenotypically related illnesses. ► SMD youths did not differ from healthy children in any comparison. Controversy exists about whether non-episodic irritability (operationalized as severe mood dysregulation, SMD) should be considered a developmental presentation of pediatric bipolar disorder (BD). While assessments of brain function may address this controversy, only one fMRI study has compared BD versus SMD. We compared neural activation in BD, SMD, and controls during a motor inhibition task, since motor disinhibition is an important clinical feature in both BD and SMD. During failed inhibition, BD youths exhibited less activation in the right anterior cingulate cortex (ACC) and right nucleus accumbens relative to both SMD and healthy youths. Exploratory analyses indicate that, in BD youths, reduced activation in the right ACC may be independent of comorbid ADHD. These findings highlight neural distinctions between the phenotypically related BD and SMD populations.