Stress-Induced Inflammation and Reward Processing

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.

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.

Change in the magnitude of response bias from pre to post Trier Social Stress Task (TSST) or Placebo-TSST (P-TSST).

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)

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

The 20-item Center for Epidemiological Studies Depression Scale (CESD) is a self-report measure; participants are asked to rate how often they have experienced depressed feelings, attitudes, and behavioral symptoms during the past week (0 = rarely; 3 = most of the time). The total score range is 0 to 60, with higher scores indicating higher depressive symptoms.

Emotional reactivity and recovery from the TSST/P-TSST will be assessed using items from the Positive and Negative Affect Schedule and the Profile of Mood States. Participants rate how they feel "right now (that is, at the present moment) on a 1 (very slightly or not at all) to 5 (extremely) Likert scale. Average scores for subscales are reported, including positive and negative affect (7 items each), fatigue (8 items) vigor (5 items) and confusion (7 items). Participants also use visual analogue scales (VAS) to indicate how stressed, anxious, angry, confident, calm, socially connected and happy they are currently feeling on a 0 (not at all) to 100 (extremely) scale. The VAS are completed alongside the PANAS and three additional times during the TSST/P-TSST.

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

Boyle CC, Stanton AL, Eisenberger NI, Seeman TE, Bower JE. Effects of stress-induced inflammation on reward processing in healthy young women. Brain Behav Immun. 2020 Jan;83:126-134. doi: 10.1016/j.bbi.2019.09.023. Epub 2019 Sep 30.