Recently, researchers and clinicians have focused increased attention on a group of children with severe mood and behavioral dysregulation. These children are characterized by impairing symptoms that include abnormal baseline mood (i.e. irritability, anger, and/or sadness), hyperarousal (e.g. insomnia, agitation, distractibility), and increased reactivity to negative emotional stimuli. Because this syndrome shares many clinical features with bipolar disorder (BPD), there is considerable debate as to whether these children should be diagnosed with BPD. However, children with this syndrome lack the cardinal symptoms of BPD (i.e. euphoria, elation, grandiosity, decreased need for sleep, and increased goal-directed activity). Similarly, while many of these children fit diagnostic criteria for other DSM-IV diagnoses (including attention deficit hyperactivity, oppositional defiant, major depressive and/or conduct disorders), these diagnoses capture heterogeneous clinical populations that include many children who do not exhibit the symptoms noted above. Therefore, the first goal of this project is to identify reliably a group of children with severe mood and behavioral dysregulation in order to characterize them clinically and follow them longitudinally. In addition, since there are no controlled trials to guide treatment of these severely impaired children, we will conduct a double-blinded, placebo controlled trial of lithium. The goals of this trial will be to test the efficacy of lithium, and to investigate whether lithium response, which has been associated with neurotrophic effects and with changes in phosphoinositide signaling in bipolar patients, has similar effects in this group of patients. Finally we will test two preliminary hypotheses regarding the possible pathophysiology of their symptoms. To do so, we will use affect-modulated startle techniques parallel to those being used in a study of children with unequivocal BPD (Protocol # 00-M-0198) as well as functional MRI.