The purpose of this research study is to better understand anhedonia in Major Depressive Disorder by investigating the reward-related neural and inflammatory correlates.
Background: Despite extensive research on the treatment of Major Depressive Disorder (MDD) relapse rates are as high as 80%. Of those, 30-40% fall into the severe spectrum called treatment resistant depression (TRD) as they fail to respond to at least two lines of antidepressant treatment interventions. TRD has been linked with anhedonia, the inability to experience pleasure or interest in usually enjoyable activities. The neurobiology of anhedonia is poorly understood with recent literature examining an inflammatory association and linking it to deficits in reward-related brain circuitry. The present study examines neurobiological correlates of anhedonia in MDD and TRD, specifically C-Reactive Protein (CRP), IL-6 and ventral striatal (VS) activity. The study also explores whether VS activity mediates the association between inflammation and anhedonia.
Study Type
OBSERVATIONAL
Enrollment
60
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
Basal inflammatory marker assessment
Quantify the profile of basal inflammatory markers (IL-6 and C-reactive protein) in blood. Blood will be collected within an hour after consent and will be processed by 3 hours.
Time frame: 1 hour
Behavior during reward-based task - Monetary Incentive Delay Task
Participants will complete the Monetary Incentive Delay (MID) task, a reward-based task, while undergoing functional magnetic resonance imaging (fMRI). Results will include button press reaction time for the MID task.
Time frame: 30 minutes
Behavior during reward-based task - Reward Probabilistic Reversal Learning Task
Participants will complete a Reward Probabilistic Reversal Learning Task, a reward-based task, while undergoing functional magnetic resonance imaging (fMRI). Results will include choice behavior, either choice A or choice B, (button press) for this task.
Time frame: 30 minutes
Blood oxygen level dependent (BOLD) activation during reward-based tasks
Participants will undergo functional magnetic resonance imaging (fMRI) while completing the tasks in Outcome 2. Ventral striatum activation during the tasks will be measured by % BOLD signal change. The expected signal change is between .1-.8%.
Time frame: 1 hour
Mediation model between inflammation and anhedonia
Hierarchical linear mediation analysis will be used to determine if BOLD signal in the ventral striatum during reward based tasks significantly mediates the link between inflammation and anhedonia.
Time frame: 3 hours
Exploratory inflammatory marker assessment
Exploratory analysis of pro (IL-8, TNF-alpha) and anti- inflammatory marker (IL-10) from blood samples will be conducted. All cytokines will be transformed log(x+1) to correct a positive skew and to maintain a meaningful zero. Outlier cytokine values (\>3 standard deviations above the mean) and winsorize will be identified by replacing any value with a z-score of greater than 3 SD with the value of 3 SD from the mean. This will be done for each individual cytokine. Z-scores for each individual's cytokine concentration will be calculated based on the means and standard deviations for each cytokine after winsorizing. The composite cytokine score will then be determined by calculating the mean of the basal cytokine Z-scores for each individual. A composite measure of inflammation may be statistically examined, which would involve combining these cytokines into 1-2 factors.
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Time frame: 3 hours
Exploratory analysis of reward related regions
Exploratory analysis of reward related brain regions (ventromedial prefrontal cortex and orbitofrontal cortex) will be conducted using % BOLD signal change. The expected signal change is between .1-.8%.
Time frame: 3 hours