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.
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
123
A subsample (21 per group) will complete the PET imaging.
David Crowley
Belmont, Massachusetts, United States
Behavioral Performance on the Probabilistic Stimulus Selection Task
The Probablilistic Reward Task operationalizes positive reinforcement learning
Time frame: Screening visit (Day 0)
MRI Data
Time frame: MRI scans for a total of 90 minutes take place within 30 days of Screening Visit
PET scan with raclopride
Time frame: a total of 90 minutes take place after the MRI data collection
Salivary Cortisol
Time frame: 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)
Time frame: During the MRI visit (on or before Day 30)
Follow-up Clinical Interviews
Time frame: 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.
Time frame: Administered during MRI scan (on or before Day 30)
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