Baseline and Stress-Induced Cognitive Control Deficits and Pro-Inflammatory Cytokines in Currently, Remitted, and Never Depressed Individuals

Background: Cognitive theories posit that cognitive control deficits promote depression by reducing ability to self-regulate under stress. When activated by stress and accessible to working memory, negative cognitive content and structure (i.e., schemas), may interfere with cognitive control abilities, resulting in even greater declines in executive functioning. Moreover, burgeoning evidence indicates that social stress upregulates inflammation, resulting in a pro-inflammatory phenotype that drives depression pathogenesis. However, cognitive mechanisms underlying this process are not well understood. An objective of this study was to examine depression-related deficits in cognitive control and their association with poor self-regulation. Another purpose was to evaluate the role of cognitive vulnerability in determining stress-induced declines in cognitive control. This study was the first to investigate the role of cognitive control and cognitive vulnerability (content, structure, and rumination) in shaping both resting-state and stress-induced upregulation of pro-inflammatory cytokines. Method: A clinical sample of currently depressed (n=40), remitted depressed (n=69), and healthy control (n=57) participants completed measures of cognitive content (core beliefs, dysfunctional attitudes), self-schema structure, rumination, depressive symptoms, and a battery of affective cognitive control tasks assessing inhibition, updating, and shifting. Salivary levels of four pro-inflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) and updating abilities were assessed before and after a laboratory social stress induction. Depressive symptoms were evaluated at 2-week and 6-month follow-up. Results: Depressed individuals evinced deficits in inhibition and updating, which were associated with rumination, but not in shifting. As hypothesized, core beliefs and self-schema structure predicted declines in updating abilities following stress, and several cognitive control and vulnerability variables were related to baseline and stress-induced changes in cytokines. A fairly consistent pattern of findings emerged whereby deficits in cognitive control were associated with greater resting-state and stress-induced inflammation among individuals with low, and not high, cognitive vulnerability. Moreover, greater inflammatory reactivity to the stressor predicted decreases in depressive symptoms at follow-up. Conclusion: Cognitive content and structure are important in determining stress-induced declines in cognitive control, and inflammation represents a biological pathway through which cognitive vulnerability and cognitive control may influence depression. Theoretical and clinical implications of findings and directions for future research are discussed