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

Sex, Hormones and GABA in Stress Induced Anhedonia in Depression

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.

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 251

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 23 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Young adults (ages 18 to 25).

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Network-specific effective connectivity	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	Baseline
GABA concentration	Region-specific GABA concentration measured in rostral anterior cingulate cortex and dorsolateral prefrontal cortex	Baseline

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Collaborators: Massachusetts General Hospital; Brigham and Women's Hospital
• Investigators: Principal Investigator: Diego A Pizzagalli, Ph.D., McLean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): June 15, 2022

Study Registration Dates

• First Submitted: January 20, 2017
• First Submitted That Met QC Criteria: January 23, 2017
• First Posted (Estimated): January 25, 2017

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Depression; Stress; Androgens; GABA
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Mood Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Depression; Depressive Disorder; Anhedonia; Depressive Disorder, Major
• Other Study ID Numbers: 2016P000693

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No