Patient description: A 46-year-old Asian woman with MDD complains of persistent feelings of sadness and loss of interest in daily activities. She states that her mood is still depressed most of the days. She complains of loss of energy and feelings of worthlessness nearly every day. She is on anti-depressants for the past 6 months, but the symptoms are still present. She does not drink alcohol or smoke. She used to exercise every day for at least 30 min., but she doesn't have enough energy to do so for the past 3 weeks. She also has some digestive issues recently. She is married and has 4 children. She is menopausal. Her husband was diagnosed with colon cancer a year ago and is undergoing chemotherapy. Her past medical history is unremarkable. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 13.0-21.0,  Major Depressive Disorder Major Depressive Disorder, Recurrent Major Depressive Disorder, Remitted Adolescents from the ages of 13 to 21, male or female. 2. Subjects with MDD (Groups 2, 3 & 4) Must have a diagnosis of Major Depressive Disorder (MDD) Single episode or recurrent; moderate to severe The MDD diagnosis is based on the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children Past and Lifetime (K-SADS-PL) This semi-structured psychiatric interview will be administered by a psychiatrist, Ph.D. level psychologist, or equivalent professional with extensive clinical experience Must have a Childhood Depression Rating Scale-Revised (CDRS-R) score of ≥ 40 Must have a Clinical Global Impression Severity (CGI-S) Scale of ≥ 4 3. Group 1: (Healthy Controls; 50 Subjects): Healthy volunteers who are 13-21 years of age with no current or lifetime mental health diagnoses and no current or lifetime psychotropic medication treatment. 4. Group 2: (50 subjects): Subjects with moderate to severe MDD for which an SSRI has been clinically indicated If initiating SSRI treatment, medication must be started ± 7 days of the baseline visit Subjects and parents in group 2 will be eligible to return in 6-8 weeks for a follow up visit that includes mood assessments and evaluations  For all Subjects: 1. Contraindications to MRI/MRS, as determined by the MRI safety screen and MRI safety codes. 2. Subjects who are judged by the Principal Investigator to be at imminent risk for self-harm or suicide as indicated by interview or C-SSRS. 3. Pregnancy or suspected pregnancy in females. 4. Metal in the head (except the mouth*), implanted medication pumps, cardiac pacemaker (*subjects with braces will be excluded from MRI/MRS portion of the study only) 5. Prior brain surgery. 6. Risk for increased intracranial pressure such as a brain tumor. 7. Any unstable medical condition. 4.2.1 for Healthy Control Group only: 1. Current or past mental health diagnoses in subjects or first degree relatives of subjects. 2. Current or past mental health medications. 4.2.2 for MDD Groups only: 1. Primary Axis I or II disorder other than MDD. 2. Unprovoked seizure history, seizure disorder, history of febrile seizures, first degree relative with epilepsy 3. Taking medication(s) that lower seizure threshold 4. Any significant findings on the TMS adult safety screen (TASS). 4.2.3 for Group 2 only: 1. Subject has started SSRI medication more than 7 days prior to the baseline visit