Characterization and Treatment of Adolescent Depression

* INCLUSION CRITERIA: * Youths who meet DSM 5 criteria for Major Depressive Disorder (Group 1) Inclusion criteria 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). * Feelings of worthlessness or excessive or inappropriate guilt nearly every day (e.g., ruminating over minor past failings). * Diminished ability to think or concentrate, or indecisiveness, nearly every day (e.g., appears easily distracted, complains of memory difficulties). * Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideas without a specific plan, or a suicide attempt or a specific plan for committing suicide * Symptoms cause clinically significant distress or impairment in social, occupational/academic, or other important areas of functioning. * The episode is not attributable to the physiological effects of a substance or to another medical condition. INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS: * Adolescent Healthy Volunteers (Group 3a) * Youth 11 to 17 years of age at time of enrollment in Characterization * the adolescent must be competent to assent; parents must be able comprehend and provide permission for their child (consent). * Participants will be willing to participate in NIMH IRB approved research protocols. Minors will be asked to sign assent forms and their parents will sign the consent form. * Participants will be willing to undergo an evaluation, which may include a psychiatric interview, review of medical history (including Tanner staging for minors), and pregnancy testing. * Speaks English. * Have an identified primary care clinician. * Adult Healthy Volunteers (Group 3b) * Adults 18 to 30 years of age at time of enrollment in Characterization * Subjects must be competent to consent. * Participants will be willing to participate in NIMH IRB approved research protocols. * Participants will be willing to undergo an evaluation, which may include a psychiatric interview, review of medical history, and pregnancy testing (for females). * Speaks English. * Has an identified primary care clinician. INCLUSION CRITERIA FOR PARENTS OF ENROLLED YOUTH (Group 4): * Are the biological parent or legal guardian of an enrolled adolescent (who is a healthy volunteer or has MDD) participant; Parents of those with s-MDD are historical only; none enrolled after Dec 2021. * Those of all ages are eligible if they are a parent of a currently enrolled participant EXCLUSION CRITERIA: (All patients) -Exclusion Criteria for MDD patients (Group 1) * Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, bipolar disorder, more than mild Autism Spectrum Disorder, current Anorexia Nervosa or other severe Eating Disorder. * Intellectual disability (clinically identified or IQ \< 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. * Meets DSM-5 criteria 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. -Exclusion criteria for youths meeting modified DSM criteria for Subthreshold Depression (Group 2) (this cohort is historical only; previously n=200 to be enrolled; ceased enrolling this population with Amendment J (2022); none enrolled after Dec 2021): * Intellectual disability (clinically identified or IQ \< 70). * Any serious medical condition (such as epilepsy, heart disease requiring medication) by self and parent report. * Past or current diagnosis of a manic or hypomanic episode, major depression), schizophrenia, schizophreniform disorder, schizoaffective illness, Tourette Disorder, or Autism Spectrum Disorder, Anorexia Nervosa or other severe Eating Disorder. * Meets DSM-5 criteria for alcohol or substance abuse within the last three months by self and parent report. * NIMH IRP Employees/staff and immediate family members will be excluded from the study per NIMH policy. -Healthy volunteer youths and adults exclusion criteria: * Intellectual disability (clinically identified or IQ \< 70). * Any serious medical condition (such as epilepsy, heart disease requiring medication) by self and parent report. * Past or current diagnosis of any mood disorder (manic or hypomanic episode, major depression), anxiety disorder (except specific phobia), Obsessive Compulsive Disorder (OCD), Post-Traumatic Stress Disorders (PTSD), Conduct Disorder, schizophrenia, schizophreniform disorder, schizoaffective illness, Tourette Disorder, or Autism Spectrum Disorder. * Meets DSM-5 criteria for alcohol or substance abuse within the last three months by self and parent report; for adults, past history of substance dependency or substance abuse within the last three months by self-report. Parents of enrolled participants (group 3) exclusion criteria: --Parents who are unable to understand or read English well enough to complete the study interview and tests.