Neuroimaging Studies of Reward Processing in Depression

Sponsor

Mclean Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03026036

Collaborator

(none)

123

Enrollment

Location

Actual Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	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 Design

Study Type:

Observational

Actual Enrollment :

123 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Neuroimaging Studies of Reward Processing in Depression

Actual Study Start Date :

Apr 1, 2016

Actual Primary Completion Date :

Mar 1, 2021

Actual Study Completion Date :

Mar 1, 2021

Arms and Interventions

Arm	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.

Arm

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.

Healthy control participants

Radiation: PET Scan with Raclopride

A subsample (21 per group) will complete the PET imaging.

Outcome Measures

Primary Outcome Measures

Behavioral Performance on the Probabilistic Stimulus Selection Task [Screening visit (Day 0)]
The Probablilistic Reward Task operationalizes positive reinforcement learning
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 [Administered during MRI scan (on or before Day 30)]
The instrumental learning task is designed to measure participant learning from reward and punishment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)