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

Sponsor

Mclean Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03031665

Collaborator

Brigham and Women's Hospital (Other), Massachusetts General Hospital (Other)

144

Enrollment

Location

54.9

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Using an innovative multi-modal imaging approach, this study investigates the role of the neurochemical gamma-aminobutyric acid (GABA), brain activity, as well as hormones in understanding sex differences in Major Depressive Disorder (MDD). Further, the investigators will link these markers to symptoms of depression.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

144 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Sex, Hormones and GABA in Stress Induced Anhedonia in Depression

Actual Study Start Date :

Oct 1, 2017

Anticipated Primary Completion Date :

Apr 30, 2022

Anticipated Study Completion Date :

Apr 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Current MDD Subjects experiencing a current episode of Major Depressive Disorder.
Remitted MDD Subjects who have a history of Major Depressive Disorder, but have not had a depressive episode for at least two months.
Control Subjects Subjects who have no history of clinical depression or other psychological disorder.

Outcome Measures

Primary Outcome Measures

Blood oxygen level-dependent (BOLD) activation in response to stress [Baseline.]
Region-specific BOLD activation in response to stress in hypothalamus, amygdala, medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, and hippocampus

Secondary Outcome Measures

Network-specific effective connectivity [Baseline]
Region-specific resting state connectivity of two networks (1) hypothalamus and amygdala, with medial prefrontal cortex and orbitofrontal cortex; and (2) hypothalamus and amygdala, with hippocampus
GABA concentration [Baseline]
Region-specific GABA concentration measured in rostral anterior cingulate cortex and dorsolateral prefrontal cortex

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.