Major depressive disorder (MDD) is a familial recurrent illness that significantly interferes with the child's normal development and is associated with increased risk for suicidal behaviors and psychiatric and psychosocial morbidity. Although most children and adolescents recover from their first depressive episode, 30-70%, in particular those with familial history of MDD, comorbid psychiatric disorders, dysthymia, subsyndromal symptoms of depression, anxiety, negative cognitive style, and exposure to negative life events (e.g., family conflicts and abuse) will experience one or more depressive recurrences during their childhood, adolescence, and adulthood. Depressed youth who present with psychosis, psychomotor retardation, pharmacological induced hypomania/mania, and/or family history of bipolar disorder are at high risk to develop bipolar disorder.