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

• Published in: Journal of affective disorders Vol. 296; pp. 465 - 475
• Main Authors: Zainal, Nur Hani, Newman, Michelle G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-01-2022
• Subjects: Adult; Affective neuroscience; Anxiety; Cross-Sectional Studies; Depression; Depressive Disorder, Major - epidemiology; Executive Function; Executive functioning; Generalized anxiety disorder; Humans; Inflammation - epidemiology; Longitudinal; Major depressive disorder; Mediation; Panic disorder; Worry; Affective neuroscience; Longitudinal; Generalized anxiety disorder; Panic disorder; Executive functioning; Mediation; Major depressive disorder; Worry
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2021.08.077

•Time 1 MDD and GAD severity predicted increased inflammation 9 years later.•T1 PD severity did not forecast future IL-6, CRP, and fibrinogen levels.•Heightened T2 inflammation predicted lower executive function after 9 years.•T1 MDD, GAD, and PD independently related to less EF capacity following 18 years.•Findings remained after adjusting for BMI, sociodemographic, comorbid MDD, GAD, and PD, and lifestyle factors.
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.
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.
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.
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.
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.