(PS3-29) Reinforcement Learning and Inflammation in Major Depressive Disorder: Connecting Biomarkers to Human Behavior

Background: Elevated levels of pro-inflammatory markers have been observed with self-reported depression and anhedonia. While connections between inflammation and depression are well-established, associations with anhedonia and performance on reward/punishment tasks are limited. Here, we examined the associations between blood-based inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, macrophage migration inhibitory factor (MIF), C-reactive protein (CRP)) with anhedonia and reinforcement learning (RL) parameters.

Method: 35 individuals diagnosed with major depressive episode and 25 healthy controls participated (mean age 34; 72% female). After blood draw, participants completed questionnaires assessing anhedonia, including the Positive Valence Systems Scale (PVSS). Computational reinforcement learning models were fit to behavioral performance to determine RL parameters, including reward/punishment sensitivity and RL rates. Bivariate Pearson correlations assessed associations between inflammation markers and behavioral tasks and self-report measures. Significant correlations with survey measures were examined using multiple regression. Relevant covariates [age, gender, race/ethnicity, body mass index (BMI)] were included in regression models based on change in parameter estimates.

Results: IL-8 and MIF were negatively associated with reward sensitivity, suggesting a reduced sensitivity to the difference in value between choice options (r=-0.31, p=0.04; r=-0.42, p=0.004). Controlling for relevant covariates (age, gender), IL-8 negatively predicted the PVSS reward anticipation subscale score (β=-0.389, p=0.004, adjusted R²=0.11). Thus, higher inflammation was linked to both lower reward sensitivity and anticipation.

Conclusion: These results suggest inflammation is linked to decreased sensitivity to reward and reward anticipation, which may help explain the experience of lack of motivation, interest, and pleasure in rewarding activities frequently reported in depression.