The association between overweight/obesity and poor cognitive function is mediated by inflammation in patients with major depressive disorder

Background: Cognitive dysfunction is a common and core feature of major depressive disorder (MDD). Evidences exerted a potentially harmful role of obesity and higher peripheral levels of inflammation in cognitive function, but few studies have explored whether markers of peripheral inflammation might mediate the association be-tween overweight/obesity and deficits in cognitive function. Our study aimed to examine the cognitive function in MDD patients and clarify the effects of overweight/obesity and inflammatory cytokines on cognitive dysfunction in this population.Method: We used a cross-sectional design in this study. A total of 265 patients with MDD were enrolled and divided into underweight, normal weight and overweight/obese groups. The MATRICS Consensus Cognitive Battery (MCCB) was administered to measure the cognition. Plasma levels of nineteen cytokines were measured using high sensitivity multiplex bead-based assays.Results: We found overweight/obese MDD patients associated with higher plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, and macrophage inflammatory protein (MIP)-1 beta and worse performance in speed of processing and working memory. The mediation analysis found higher levels of IL-8 (direct: beta =-0.591 (95 % Confidence Interval (CI):-1.0 to-0.2), P = 0.002; indirect: beta = 0.060 (95 % CI.: 0.0-0.2), P = 0.032) and TNF-alpha (direct: beta =-0.589 (95 % CI.:-1.0 to-0.2), P = 0.002; indirect: beta = 0.059 (95 % CI.: 0.1-0.2), P = 0.037) were associated with more deficits in speed of processing, and partially mediated the relationship between body mass index and speed of processing.Conclusion: Our results suggest that elevated inflammation might be one biological mechanism underlying the link between higher body mass and deficits in processing speed in patients with MDD.