Neural correlates of irritability indicate the presence of distinct neurobiological processes for children with symptoms of "severe mood dysregulation" (SMD) compared with those who have bipolar disorder.

Youth with SMD reported greater arousal following negative feedback than children with bipolar disorder and controls and responded to negative feedback with significantly greater activation of the anterior cingulate cortex and medial frontal gyrus than healthy subjects.

Compared with youth who have SMD and healthy children, children with bipolar disorder displayed greater superior frontal gyrus activation and decreased insula activation following negative feedback.

These findings are important because they indicate that children who experience extreme irritability in the face of frustration have a neurobiological process distinct from that seen in bipolar disorder and may warrant a diagnosis of SMD.