Sex, Hormones and Gamma-Aminobutyric Acid (GABA) in Stress Induced Anhedonia in Depression

The goals of this research are to investigate: (1) functional and neurochemical features associated with depression irrespective of clinical state; (2) moderating effects of hormones on stress circuitry in MDD; and (3) sex differences in symptoms. To this end, the study is enrolling adults with current depression and remitted depression, along with a control group of psychiatrically health adults. Participants will have an magnetic resonance imaging (MRI) exam involving multiple imaging techniques (functional, structural, spectroscopic) while performing computer-based tests. Additional questionnaires and tests will be done outside the scanner to assess current symptoms and hormone levels. The integration of laboratory-based measures of reward and stress sensitivity, with state-of-the-art imaging techniques and hormonal assessments promises to provide novel insights in the sex-dependent manifestation and pathophysiology of MDD.

Inclusion criteria

for all participants.

• Males and females aged 18 through 25
• Capable of providing written informed consent, and fluent in English
• Right-handed
• Absence of any psychotropic medications for at least 2 weeks
• Female subjects will be scheduled to participate during the follicular phase of their menstrual cycle

Inclusion criteria

for "Current MDD" group:

• Meets inclusion criteria for all subjects, plus:
• Meets diagnostic criteria for a current episode of Major Depressive Disorder (MDD), as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

Inclusion criteria

for "Remitted MDD" group:

• Meets inclusion criteria for all subjects, plus:
• History of MDD as defined by DSM-5, but in remission for the past two months
• Absence of anxiety disorder for the past two months

Exclusion criteria

for all participants:

• History of psychiatric illnesses, other than depression or anxiety disorders among the Current MDD and Remitted MDD groups.
• History of psychotic episodes, suicidal ideation, or of electroconvulsive therapy (ECT) treatment
• Use of hormone replacement therapy, or of anabolic steroids.
• Use of hormonal contraceptives is permitted for female subjects only if the subject has regular menses
• Failure to meet any MRI safety requirements
• Serious or unstable medical illness, or history of neurological disease or damage
• History of use of cocaine, stimulants, or dopaminergic drugs
• History of substance use disorder or alcohol use disorder (as these terms are defined by DSM-5); except depressed subjects may have a history of 'Mild' substance/alcohol use disorder only if it ended as least 12 months ago.