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.