Depression and worry symptoms predict future executive functioning impairment via inflammation

Background Scar models posit that heightened anxiety and depression can increase the risk for subsequent reduced executive function (EF) through increased inflammation across months. However, the majority of past research on this subject used cross-sectional designs. We therefore examined if elevated generalized anxiety disorder (GAD), major depressive disorder (MDD), and panic disorder (PD) symptoms forecasted lower EF after 20 months through heightened inflammation. Methods Community-dwelling adults partook in this study (n = 614; MAGE = 51.80 years, 50% females). Time 1 (T1) symptom severity (Composite International Diagnostic Interview - Short Form), T2 (2 months after T1) inflammation serum levels (C-reactive protein, fibrinogen, interleukin-6), and T3 (20 months after T1) EF (Brief Test of Adult Cognition by Telephone) were assessed. Structural equation mediation modeling was performed. Results Greater T1 MDD and GAD (but not PD) severity predicted increased T2 inflammation (Cohen's d = 0.21-1.92). Moreover, heightened T2 inflammation forecasted lower T3 EF (d = -1.98 to -1.87). T2 inflammation explained 25-32% of the negative relations between T1 MDD or GAD and T3 EF. T1 GAD severity predicting T3 EF via T2 inflammation path was stronger among younger (v. older) adults. Direct effects of T1 MDD, GAD, and PD forecasting decreased T3 EF were found (d = -2.02 to -1.92). Results remained when controlling for socio-demographic, physical health, and lifestyle factors. Conclusions Inflammation can function as a mechanism of the T1 MDD or GAD-T3 EF associations. Interventions that successfully treat depression, anxiety, and inflammation-linked disorders may avert EF decrements.