The primary objective of this initiative is to implement a prospective study that will allow us to identify and validate biosignatures of response to treatments for depression and depression outcome (using an integrated array of participant specific data: socio-demographic, lifestyle, clinical and behavioral assessments, fluid-based biomarkers, genomics, neuroimaging, EEG, and cell-based assays) in a longitudinal cohort of subjects with elevated symptoms of a depressive disorder.

Symptom remission across various treatment options will be assessed using questionnaires for symptom changes, antidepressant treatment tolerability and overall quality of life. Other outcomes generated from this study will include rate of change in quantitative measures of brain function, of depression relevant brain regions correlated with systems-levels behavior and other functional neuro-circuitry MRI measures. Rate of change of specified biochemical biomarkers will also be assessed.

Integration of these measures will provide an unmatched understanding into the mechanisms of depression and hold tremendous promise for better disease treatment and associated outcomes.

D2K is a 10-year natural history, longitudinal, prospective study of a cohort of 2,500 participants that will help uncover the socio-demographic, lifestyle, clinical, psychological, and neurobiological factors that contribute to antidepressant treatment response: remission, recurrence, relapse and individual outcomes in depressive disorders. As this is an exploratory study, we will assess a comprehensive panel of carefully selected participant specific parameters: socio-demographic (age, sex, gender, race, ethnicity, economic); life habits (physical activity, substance use); clinical (medical history, anxious depression, early life trauma), biological (biomarkers in blood, saliva, urine, stool), behavioral (cognitive, emotional), neurophysiological (EEG), and neuroimaging (magnetic resonance imaging; MRI) with the goal of developing the most robust predictive models of depression treatment response and of outcomes.

Clinician rated assessments, participant rated assessments, blood, saliva, stool, and urine collection, EEG, and MRI will be performed during the duration of the study. An optional m-health study may be collected continuously via a phone application and/or wristband over the course of the study. With this said, due to the nature of the protocol and the large number of research participants, we expect some appointments that include procedures and assessments to be missed within an expected study time frame. We will attempt to complete any missed appointments at the next scheduled visit. For the purposes of this study, missed procedures and/or assessments are not considered protocol deviations. In addition, the schedule of assessments to be completed will vary from time to time within this longitudinal study to help balance the data between age, sex, biological gender, gender identity, sexual orientation, gender expression, and diagnosis breakdown of our enrolled participants for data analyses.

The schedule of assessments will NOT exceed the following:

1. Monthly Surveys: 12 times a year
2. MRI: up to 4 times a year
3. EEG: up to 4 times a year
4. Biospecimen collection: up to 4 times a year
5. Cognitive Behavioral Tasks: up to 4 times a year
6. Extensive Self-report and Clinician rated assessments: 4 times a year
7. Stool Sample collection: up to 4 times a year
8. Optional M-health: Duration of the study (starting from Baseline) Participants will be compensated based on the study activity they complete and will not exceed the total amount (per year) that is approved by the IRB. No study procedures will be conducted until signed informed consent has been obtained from the participant. Details regarding informed consent procedures are included in section 8.

Procedures specific to youth 17 years old or younger: Participants will complete the questionnaires that have been normed and validated to their age with the assistance of study staff. Forms may also be completed by participant's parent(s)/guardian(s)/LAR as needed.

Criteria for Inclusion of participants:

A potential participant will be eligible for participation in this study if the following criteria are met:

1. Male and female adult or youth aged 10 and older of any race or ethnicity.
2. Ability to speak, read, and understand English. However, the parent(s) or legal guardians of minors may either speak English or Spanish as the consenting process can be conducted bilingually.
3. A lifetime or a current diagnosis of a mood disorder based upon a semi-structured diagnostic interview.
4. Adults age 18 and older must be able to provide written informed consent; for youth younger than age 18, a parent or legal guardian must provide written informed consent, and the child or teen must provide written informed assent.

Eligibility for Healthy Controls

For comparison purposes, potential health control participants who do NOT have a psychiatric diagnosis will be enrolled as part of the healthy control arm of this study.

1. Male and female adult or youth aged 10 and older of any race or ethnicity.
2. Ability to speak, read, and understand English. However, the parent(s) or legal guardians of minors may either speak English or Spanish as the consenting process can be conducted bilingually.
3. Adults age 18 and older must be able to provide written informed consent; for youth younger than age 18, a parent or legal guardian must provide written informed consent, and the child or teen must provide written informed assent.

Criteria for Exclusion of Participants

A potential participant will NOT be eligible for participation in this study if any of the following criteria are met:

1. History of schizophrenia, schizoaffective disorders or chronic psychotic disorders based upon a semi-structured diagnostic interview.
2. Diagnosis of human immunodeficiency virus (HIV) or hepatitis B or C (human immunodeficiency virus (HIV) testing is not required for this study).
3. Unable to provide a stable home address and contact information.
4. Has any condition for which, in the opinion of the investigator or designee, study participation would not be in their best interest (including but not limited to cognitive impairment, unstable general medical condition, intoxication, active psychosis) or that could prevent, limit, or confound the protocol-specified assessments.
5. Requires immediate hospitalization for psychiatric disorder or suicidal risk as assessed by a licensed study clinician.

Eligibility for Healthy Controls

A potential Healthy Control participant will NOT be eligible for participation in this study if any of the following criteria are met:

1. A lifetime or a current history of a mood disorder based upon a semi-structured diagnostic interview.
2. Meets any exclusion criteria as part of the main D2K study interview.

The following group is being targeted for this observational study:

1. Depressed patients
2. Lifetime or Current Diagnosis of a Mood Disorder
3. Bipolar Disorder
4. Health Controls with NO Psychiatric Diagnosis ( For Comparison Purposes)