This study aims to assess whether phenotyping-guided intervention selection is superior to intervention selection without phenotyping guidance (i.e., routine clinician and patient judgment regarding treatment selection) for depression.

This study will classify patients seen in the Depression Clinic of the UCSF Department of Psychiatry and Behavioral Sciences into one of five phenotypes (subtypes), including: 1) Anhedonia, 2) Cognitive deficits, 3) Stress sensitivity, 4) Anxious distress, and 5) Grief.

After phenotyping, participants will be randomized to receive phenotype-specific intervention (PSI) or care as usual (CAU).

Inclusion Criteria:

• Participant is able to provide informed consent
• English speaker
• 18 years of age or older at time of consent
• Meets DSM-5 criteria for Major Depressive Disorder
• The subject meets eligibility criteria for at least one study phenotype as determined by assessments, imaging and/or clinical judgment.
• PHQ-8 score at baseline of >= 10
• Scheduled for or completed intake in UCSF outpatient psychiatry

Exclusion Criteria:

• Unstable or untreated medical or psychiatric condition based on clinical assessment by investigator(s)
• Significant risk of suicidal or violent behavior as determined by clinical judgement
• In the Investigators' opinion, the subject is not capable of adhering to the protocol requirements, or the subject has a history of poor or suspected poor compliance in clinical research studies, or the subject has a history of poor or suspected poor compliance to antidepressant medication or that study participation is not in their best interest (e.g., different treatment is indicated given their clinical presentation)
• Pregnant or breastfeeding or planning to become pregnant during the study