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.

© This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/

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Work Title Inflammation mediates depression and generalized anxiety symptoms predicting executive function impairment after 18 years
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Open Access
Creators
  1. Nur Hani Zainal
  2. Michelle G. Newman
Keyword
  1. Executive functioning
  2. Affective neuroscience
  3. Worry
  4. Generalized anxiety disorder
  5. Panic disorder
  6. Major depressive disorder
  7. Longitudinal
  8. Mediation
License CC BY-NC-ND 4.0 (Attribution-NonCommercial-NoDerivatives)
Work Type Article
Publisher
  1. Elsevier BV
Publication Date January 2022
Publisher Identifier (DOI)
  1. 10.1016/j.jad.2021.08.077
Source
  1. Journal of Affective Disorders
Deposited June 15, 2022

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Version 1
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  • Created
  • Added Zainal-in p-Inflammation mediates depression a-1.pdf
  • Added Creator Nur Hani Zainal
  • Added Creator Michelle G. Newman
  • Published
  • Updated Keyword, Description Show Changes
    Keyword
    • Executive functioning, Affective neuroscience, Worry, Generalized anxiety disorder, Panic disorder, Major depressive disorder, Longitudinal , Mediation
    Description
    • 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
    • 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.
  • Updated