Scientists scan brains to find the off-switch for negative thoughts in depression

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Capable of understanding and complying with protocol requirements. * Participants who are fluent and literate in English and are able to understand and provide written, informed consent and any required privacy authorization prior to the initiation of any study procedures. * Male or female, 18 to 65 years. * Current diagnosis of MDD who are currently depressed defined by the MINI. * Participants who have moderate depressive symptoms (Patient Health Questionnaire: PHQ-9 ≥ 10 or Quick Inventory of Depressive Symptomatology: QIDS-SR ≥ 11). Exclusion Criteria: * Diagnosis of Schizophrenia spectrum or other psychotic disorders. * Bipolar I Disorder. * Active suicidal ideation with a plan and intent or suicidal ideation/attempts in the past 6-12 months. * Current diagnosis of post-traumatic disorder (PTSD) defined by the MINI. * Change in the dose or prescription of medication within the 6 weeks before enrolling in the study that could affect brain functioning. * Moderate to severe substance use disorder within the last 12 months. * A positive test for drugs of abuse, including but not limited to alcohol (breath test), cocaine, marijuana, opiates, amphetamines. * Use of \> 400 mg caffeine or nicotine within the past 2 hours. Medical Conditions * History of unstable liver or renal insufficiency. * Significant and unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, hematologic, rheumatologic, or metabolic disturbance. * Moderate to severe traumatic brain injury or neurocognitive disorders with evidence of neurological deficits. * Co-morbid medical conditions, including cardiovascular (e.g., history of acute coronary events, stroke) and neurological diseases (e.g., Parkinson's, epilepsy). * Co-morbid inflammatory disorders (e.g., rheumatoid arthritis, autoimmune disorders). * Uncontrolled or unstable medical conditions deemed risky by investigators. * Chronic or acute infectious illness (e.g., HIV, SARS-CoV-2). * Current use of hormone-containing medications (excluding contraceptives), immunosuppressive medications, non-steroid anti-inflammatory drugs, or analgesics. MRI Contraindications * Contraindications for MRI (e.g., metal fragments, cardiac pacemaker). Miscellaneous * Unwillingness or inability to complete any of the major aspects of the study protocol. * Non-correctable vision or hearing problems. * Lack of understanding of English. * BMI \> 40 or \< 18.5. * Pregnancy or breastfeeding.