Neuroimaging Studies of Reward Processing in Depression

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Radiation: PET Scan with Raclopride

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 123

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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)

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	Intervention / Treatment
MDD; Patients with current Major Depressive Disorder	Radiation: PET Scan with Raclopride; A subsample (21 per group) will complete the PET imaging.
rMDD; Patients with a history of Major Depressive Disorder	Radiation: PET Scan with Raclopride; A subsample (21 per group) will complete the PET imaging.
HC; Healthy control participants	Radiation: PET Scan with Raclopride; A subsample (21 per group) will complete the PET imaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Behavioral Performance on the Probabilistic Stimulus Selection Task	The Probablilistic Reward Task operationalizes positive reinforcement learning	Screening visit (Day 0)
MRI Data		MRI scans for a total of 90 minutes take place within 30 days of Screening Visit
PET scan with raclopride		a total of 90 minutes take place after the MRI data collection
Salivary Cortisol		6 times during MRI visit (on or before Day 30), and 4 times during PET visit (on or before Day 30)
Four Blood Samples (6ml)		During the MRI visit (on or before Day 30)
Follow-up Clinical Interviews		6 months and 12 months after the MRI scanning visit
Behavioral Performance on the Instrumental Learning Task	The instrumental learning task is designed to measure participant learning from reward and punishment.	Administered during MRI scan (on or before Day 30)

Collaborators and Investigators

• Sponsor: Mclean Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: December 27, 2016
• First Submitted That Met QC Criteria: January 17, 2017
• First Posted (Estimate): January 20, 2017

Study Record Updates

• Last Update Posted (Actual): August 4, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: MRI; Depression; PET; Reward
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Raclopride
• Other Study ID Numbers: 2015P002520

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All collected IPD will be shared via NIMH Data Archive (as part of data submission agreement)
• IPD Sharing Time Frame: All collected IPD are shared every 6 months (1/15 and 7/15 of each year)
• IPD Sharing Access Criteria: Investigators may request for access for approval by the NIMH.