Twenty-two right hand–dominant, psychotropic-naive patients with MDD, aged 9 to 17 years (10 males and 12 females), and 22 healthy controls matched pairwise for age, sex, weight, and height were recruited. Mean (±SD) age of onset of the first clinical presentation in the patients with MDD was12.18 ± 2.68 years. Patients and controls were matched within a maximum of 12.96 months of each other (mean age, 5.58 ± 3.7 months). Patients were recruited after being referred to the Wayne State University Child Psychiatry outpatient clinic, Detroit, Mich. Controls were referred by pediatricians and school and community groups. Both patients and controls were paid an honorarium for their participation in this clinical research study. The Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version (K-SADS-PL)51 was administered to all subjects and their parent(s). A board-certified pediatric psychiatrist(D.R.R.) reviewed all clinical information and confirmed DSM-IV52 diagnostic criteria as well as associated medical or neurologic conditions. Exclusion criteria included lifetime history of psychosis, bipolar disorder, obsessive-compulsive disorder, anorexia or bulimia nervosa, posttraumatic stress disorder, substance abuse or dependence, Tourette syndrome or other tic-related conditions, autism, mental retardation or learning disabilities, or significant medical or neurologic conditions. Of the 22 patients, 7 had comorbid anxiety disorders, 4 had oppositional defiant disorder, 2 had attention-deficit disorder without hyperactivity, 1 had dysthymia, and 9 had MDD as their sole diagnosis. As determined by Family History–Research Diagnostic Criteria,5312 patients had at least 1 first-degree relative with MDD. No patients had a first-degree relative with bipolar disorder. Controls had no history of psychiatric illness and no family history of a DSM-IV52 Axis I disorder. Written informed consent was obtained from all parents or legal guardians and written assent was obtained from all children prior to initiating the study in compliance with the regulations of the Wayne State University Pediatric Human Investigation Committee.