Brain scans and a new drug combo aim to break the cycle of depressive rumination

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

Inclusion Criteria: For Patients With Major Depressive Disorder (MDD): * Age 18 to 45 years * Any sex * Self-identified Han Chinese * Right-handed * Education level of junior high school or above * Able to understand the informed consent form and complete self-report assessments * Meets DSM-5 diagnostic criteria for Major Depressive Disorder (MDD) based on the Structured Clinical Interview for DSM-5 (SCID) * Currently experiencing a major depressive episode * 24-item Hamilton Depression Rating Scale (HAMD-24) score \>= 21 at screening/baseline * Young Mania Rating Scale (YMRS) score \<= 5 at screening/baseline * No psychotropic medication use, other than benzodiazepines, within 6 weeks before baseline Pathological Rumination Group: * Must meet all of the following criteria: * Subjective experience of persistent and difficult-to-control ruminative thinking * Interview-confirmed pathological rumination characterized by all of the following features: * Repetitive * Intrusive * Difficult to disengage from * Unproductive * Occupying substantial mental resources * Ruminative Responses Scale (RRS) score \>= 61 Low Rumination Group: * Does not meet criteria for the Pathological Rumination Group * Ruminative Responses Scale (RRS) score \< 61 For Healthy Controls: * Age 18 to 45 years * Any sex * Self-identified Han Chinese * Right-handed * Education level of junior high school or above * Able to understand the informed consent form and complete self-report assessments * Does not meet DSM-5 diagnostic criteria for any current or past psychiatric disorder based on the Structured Clinical Interview for DSM-5 (SCID) * 24-item Hamilton Depression Rating Scale (HAMD-24) score \< 8 at screening/baseline * Young Mania Rating Scale (YMRS) score \<= 5 at screening/baseline * No psychotropic medication use within 6 weeks before baseline Exclusion Criteria: For Patients With Major Depressive Disorder (MDD): * Meets DSM-5 diagnostic criteria for any psychiatric disorder other than anxiety disorders * Major depressive disorder with psychotic features * Severe suicidal ideation or suicidal behavior * History of traumatic brain injury or loss of consciousness * Serious neurological or medical illness that, in the judgment of the investigators, may affect study participation or data interpretation, including but not limited to thyroid disorders, lupus, diabetes, active infection, or major trauma * Cardiac pacemaker or any metallic implant incompatible with MRI or PET * History of alcohol or substance dependence * Pregnant or breastfeeding * Personal history of epilepsy or family history of epilepsy in a first-degree relative * Receipt of non-pharmacological psychiatric interventions within the past 6 months, including electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), or structured psychotherapy For Healthy Controls: * Meets DSM-5 diagnostic criteria for any current or past psychiatric disorder * First-degree relative with a history of major psychiatric disorder * Severe suicidal ideation or suicidal behavior * History of traumatic brain injury or loss of consciousness * Serious neurological or medical illness that, in the judgment of the investigators, may affect study participation or data interpretation, including but not limited to thyroid disorders, lupus, diabetes, active infection, or major trauma * Cardiac pacemaker or any metallic implant incompatible with MRI or PET * History of alcohol or substance dependence * Pregnant or breastfeeding * Personal history of epilepsy or family history of epilepsy in a first-degree relative * Receipt of electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), or structured psychotherapy within the past 6 months