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): 11.0-25.0,  Depression Youths who meet DSM 5 for Major Depressive Disorder (Group 1) for Youth with MDD (all must be met) Ages 11-17 at the time of enrollment in Characterization Current diagnosis of DSM-5 Major Depressive Disorder (within the last six months from assessment) which are Five or more of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feeling sad, blue, "down in the dumps,"or empty) or observation made by others (e.g., appears tearful or about to cry). (In children and adolescents, this may present as an irritable or cranky, rather than sad, mood.) Markedly diminished interest or pleasure in all, or almost all, activities every day, such as no interest in hobbies, sports, or other things the person used to enjoy doing Significant weight loss when not dieting or weight gain (e.g., a change of more than 5 percent of body weight in a month), or decrease or increase in appetite nearly every day Insomnia (inability to get to sleep or difficulty staying asleep) or hypersomnia (sleeping too much) nearly every day Psychomotor agitation (e.g., restlessness, inability to sit still, pacing, pulling at clothes or clothes) or retardation (e.g., slowed speech, movements, quiet talking) nearly every day Fatigue, tiredness, or loss of energy nearly every day (e.g., even the smallest tasks, like dressing or washing, seem difficult to do and take longer than usual)  (All patients) - for MDD patients (Group 1) Meets for schizophrenia, schizophreniform disorder, schizoaffective illness, bipolar disorder, more than mild Autism Spectrum Disorder, Anorexia Nervosa or other severe Eating Disorder Intellectual disability (clinically identified or IQ less than 70) For subjects with major depression or sub-threshold major depressive episode: Symptoms of depression are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition by self and parent report Currently pregnant or lactating by self and parent report and urine pregnancy test Meets DSM-5 for alcohol or substance use disorder (excluding tobacco and nicotine use) within the last three months. This is determined solely by clinical interview of child and parent (e.g. KSADS) Current active suicidal ideation (i.e., presence of intent for engaging in suicidal behaviors). Youths with passive suicidal ideation and/or past active suicidal ideation are still eligible Participants with repeated self-harm occurring in the context of inter-personal conflict NIMH IRP Employees/staff and immediate family members will be excluded from the study per NIMH policy. -