Stress-Induced Inflammation and Reward Processing

Study Overview
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Brief Summary
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Anhedonia, or loss of interest or pleasure, is a key feature of depression and transdiagnostic construct in psychopathology. Both theory and compelling evidence from preclinical models implicates stress-induced inflammation as a key psychobiological pathway to anhedonic behavior; however, this pathway has not been demonstrated in human models. Further, although anhedonia may reflect dysregulation in multiple dimensions of reward, the extent to which stress-induced inflammation alters these dimensions is unclear. The current placebo controlled study used a standardized laboratory stressor task to elicit an inflammatory response in a sample of a healthy young women and evaluate effects of stress-induced inflammation on multiple behavioral indices of reward processing.

Detailed Description
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In this study we propose to examine the association between psychosocial stress, the stress-induced inflammatory response, and reward processing in a female undergraduate sample. Specifically, we will 1) examine effects of an acute psychosocial stressor on reward processing; 2) evaluate the association between stress-related changes in inflammation and reward processing; and 3) test key vulnerability factors that may moderate the association between stress and reward. To achieve these goals, this study will recruit 60 female undergraduate students to test effects of stress on reward processing in a 3.5 hour laboratory session. Participants will be randomly assigned to either experience a laboratory stressor or a placebo control, and will complete reward tasks 90 minutes post stress/placebo onset, at which point the peripheral inflammatory response to stress reaches its peak. The reward tasks are computerized behavioral tasks that assess three domains of reward processing: reward-learning, reward motivation, and reward sensitivity. Throughout the session, all participants will complete self-report measures of affect and provide blood and saliva samples for evaluation of the psychological and physiological stress response. Within one week prior to the session, participants will attend a 1 hour visit in which they complete baseline reward tasks and self-report questionnaires assessing mood, personality, early life stress, and health behaviors. In total, participants will complete two visits, with a duration of 4.5 hours. This study builds upon prior studies demonstrating immediate effects of acute stress on reward processing, and further tests for delayed effects of acute stress on reward processing. Furthermore, this will be the first study to examine inflammation as a mechanism linking stress to deficits in reward processing. Findings may inform theory of depression etiology and contribute to more specialized treatment that is targeted at specific symptoms of depression.

Official Title
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Stress-Induced Inflammation and Reward Processing

Conditions
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Stress, Psychological

Intervention / Treatment
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* Behavioral: Stress; Trier Social Stress Task
* Behavioral: Placebo Trier Social Stress Task


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English fluency Age 18-28 Biologically female Exclusion Criteria: Current illness Presence or history of major medical conditions Current or past diagnosis of alcohol use disorder Use of tobacco Use of immune-altering medications Current pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 28 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Acute Psychosocial stress vs. Non-stress active control
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stress; Trier Social Stress Task<br>5 min challenging speech task, 5 min challenging math task; performed in front of evaluators | Behavioral: Stress; Trier Social Stress Task<br>* Standardized acute psychosocial stressor<br>|
| Active Comparator: Placebo Trier Social Stress Task<br>5 min speech task, 5 min math task; performed alone | Behavioral: Placebo Trier Social Stress Task<br>* Active control version of the TSST<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probabilistic Reward Task - Reward Responsiveness | Change in the magnitude of response bias from pre to post Trier Social Stress Task (TSST) or Placebo-TSST (P-TSST). | Pre-TSST/P-TSST and 90 min post-TSST/P-TSST | 
| Effort Expenditure for Rewards Task - Reward Motivation | Change in amount of hard trials chosen from pre to post-TSST/P-TSST (overall, and at 3 levels of probability of potential rewards; low, medium, and high) | Pre-TSST/P-TSST and 120 min post-TSST/P-TSST | 
| Attentional Bias Task | Change in attentional bias from pre to post-TSST/P-TSST | Pre-TSST/P-TSST and 110 min post-TSST/P-TSST | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effort Expenditure for Rewards Task - Reward Sensitivity | Strength of the relationship between changes in reward magnitude and high effort trial choice as a function of degree of change in IL-6 following acute stress | 120 min post-TSST | 
| Face Morphing Task | Change in latency to detect emotional expressions | Pre-TSST/P-TSST and 115 min post-TSST/P-TSST | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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reward processing