Inflammation mediates depression and generalized anxiety symptoms predicting executive function impairment after 18 years

Introduction: Scar theories propose that elevated depression and anxiety can predispose people to future decreased executive function (EF) via heightened inflammation across decades. However, more longitudinal (versus cross-sectional) research on this topic is needed. Objective: We thus investigated if increased major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) severity predicted EF decrement 18 years later via heightened inflammation. Method: Community-dwelling adults participated in this study. Time 1 (T1) MDD, GAD, and PD severity (Composite International Diagnostic Interview–Short Form), T2 inflammation (interleukin-6, C-reactive protein, and fibrinogen blood levels concentration), and T2 and T3 EF (Brief Test of Adult Cognition by Telephone) were measured. The waves of assessment were spaced approximately 9 years apart. Structural equation modeling was conducted. Results: Higher T1 MDD and GAD (but not PD) severity forecasted elevated T2 inflammation (Cohen's d = 0.116–0.758). Greater T2 inflammation level predicted lower T3 EF following 9 years (d = -0.782–-0.636). The T1 MDD–T3 EF and T1 GAD–T3 EF negative associations were mediated by T2 inflammation, and explained 38% and 19% of the relations, respectively. Direct effects of higher T1 GAD and MDD predicting lower T3 EF were also observed (d = -0.585–-0.560). Significant effects remained after controlling for socio-demographic, lifestyle, medication use, various illness variables across time, and T2 EF. Conclusions: Inflammation may be a mechanism explaining the T1 MDD–T3 EF and T1 GAD–T3 EF relations. Treatments that target inflammation, worry, and/or depression may prevent future EF decline.