This study investigates stress-related signaling of glutamate and dopamine within the reward-processing circuit in Major Depressive Disorder (MDD), and whether they can be used to predict depressive symptoms in the future. This will be achieved through various neuroimaging tools (MRS, fMRI, PET), behavioral tasks, and a naturalistic follow-up design.

The overarching goals of this research are to investigate: (1) stress-induced glutamatergic abnormalities and their relation to disruption within the corticostriatal valuation circuit in MDD; (2) stress-induced DA signaling disruptions in MDD; and (3) the predictive validity of these two pathophysiological mechanisms. This will be achieved through an innovative integration of (1) proton magnetic resonance spectroscopy (MRS)-based assessments of glutamatergic metabolites in the mPFC; (2) functional magnetic resonance imaging (fMRI) probes of the corticostriatal valuation circuit with well-established stress manipulations (MAST) and assessments (cortisol and inflammatory markers); (3) positron emission tomography (PET)-based measurement of striatal DA release with well-established stress manipulations and assessments (cortisol and inflammatory markers); and (4) a naturalistic follow-up design.

General Inclusion Criteria:

• All genders, races, and ethnic origins, aged between 18 and 45
• Capable of providing written informed consent, and fluent in English
• Right-handed
• Absence of any psychotropic medications for at least 2 weeks

Inclusion Criteria for Current Depression Group (MDD):

• Current DSM-5 diagnostic criteria for MDD (as diagnosed with the use of the SCID)

Inclusion Criteria for Remitted Depression Group (rMDD):

• History of at least one major depressive episode within the past five years
• Not currently depressed

Inclusion Criteria for Healthy Control Group (HC):

• Absence of any medical, neurological, and psychiatric illness (including alcohol/substance abuse)

Exclusion Criteria:

• Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician
• Pregnant women
• Failure to meet standard MRI or PET safety requirements
• Serious or unstable medical illness
• History of seizure disorder
• History or current diagnosis of organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorder, OCD, PTSD, mood congruent or mood incongruent psychotic features, substance dependence, substance abuse within the last 12 months (with the exception of cocaine or stimulant abuse, which will lead to automatic exclusion)
• Simple phobia, social anxiety disorder, and generalized anxiety disorder will be allowed only if secondary to MDD and only in the MDD group
• History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine)
• History of use of dopaminergic drugs (including methylphenidate)
• Patients with a lifetime history of electroconvulsive therapy (ECT)

Current Major Depressive Disorder (MDD), or Remitted Major Depressive Disorder (rMDD)

All collected IPD will be shared via NIMH Data Archive (as part of data submission agreement)

All collected IPD are shared every 6 months (1/15 and 7/15 of each year)

Investigators may request for access for approval by the NIMH.