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Abstract

Objective:

Evidence from anti-inflammatory drug trials for the treatment of depression has been inconsistent. This may be ascribed to the differing symptom-specific effects of inflammation. Accordingly, the authors explored the associations between systemic inflammation and an array of individual symptoms of depression across multiple studies.

Methods:

This random-effects pooled analysis included 15 population-based cohorts and 56,351 individuals age 18 years and older. Serum or plasma concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) were measured at baseline. Using validated self-report measures, 24 depressive symptoms were ascertained in 15 cross-sectional studies, and, in seven cohorts, were also assessed at follow-up (mean follow-up period, 3.2 years).

Results:

The prevalence of depressive symptoms ranged from 1.1% (suicidal ideation) to 21.5% (sleep problems). In cross-sectional analyses, higher concentrations of CRP were robustly associated with an increased risk of experiencing four physical symptoms (changes in appetite, felt everything was an effort, loss of energy, sleep problems) and one cognitive symptom (little interest in doing things). These associations remained after adjustment for sociodemographic variables, behavioral factors, and chronic conditions; in sex- and age-stratified analyses; in longitudinal analyses; when using IL-6 as the inflammatory marker of interest; in depressed individuals; and after excluding chronically ill individuals. For four exclusively emotional symptoms (bothered by things, hopelessness about the future, felt fearful, life had been a failure), the overall evidence was strongly against an association with inflammation.

Conclusions:

These findings suggest symptom-specific rather than generalized effects of systemic inflammation on depression. Future trials exploring anti-inflammatory treatment regimens for depression may benefit from targeting individuals presenting with symptom profiles characterized by distinct inflammation-related physical and cognitive symptoms.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 1107 - 1118
PubMed: 34645276

History

Received: 23 December 2020
Revision received: 28 May 2021
Revision received: 19 July 2021
Accepted: 4 August 2021
Published online: 14 October 2021
Published in print: December 2021

Keywords

  1. Inflammation
  2. C-Reactive Protein
  3. Interleukin-6
  4. Depression Symptoms
  5. Biological Markers
  6. Epidemiology

Authors

Details

Philipp Frank, M.Sc. [email protected]
Research Department of Epidemiology and Public Health (Frank, Batty, Kivimäki) and Research Department of Behavioural Science and Health (Frank, Cadar, Steptoe), University College London; Department of Psychology and Logopedics (Jokela) and Clinicum Unit (Kivimäki), Faculty of Medicine, University of Helsinki, Helsinki.
Markus Jokela, Ph.D.
Research Department of Epidemiology and Public Health (Frank, Batty, Kivimäki) and Research Department of Behavioural Science and Health (Frank, Cadar, Steptoe), University College London; Department of Psychology and Logopedics (Jokela) and Clinicum Unit (Kivimäki), Faculty of Medicine, University of Helsinki, Helsinki.
G. David Batty, Ph.D., D.Sc.
Research Department of Epidemiology and Public Health (Frank, Batty, Kivimäki) and Research Department of Behavioural Science and Health (Frank, Cadar, Steptoe), University College London; Department of Psychology and Logopedics (Jokela) and Clinicum Unit (Kivimäki), Faculty of Medicine, University of Helsinki, Helsinki.
Research Department of Epidemiology and Public Health (Frank, Batty, Kivimäki) and Research Department of Behavioural Science and Health (Frank, Cadar, Steptoe), University College London; Department of Psychology and Logopedics (Jokela) and Clinicum Unit (Kivimäki), Faculty of Medicine, University of Helsinki, Helsinki.
Andrew Steptoe, D.Phil., F.Med.Sci.
Research Department of Epidemiology and Public Health (Frank, Batty, Kivimäki) and Research Department of Behavioural Science and Health (Frank, Cadar, Steptoe), University College London; Department of Psychology and Logopedics (Jokela) and Clinicum Unit (Kivimäki), Faculty of Medicine, University of Helsinki, Helsinki.
Mika Kivimäki, Ph.D., F.Med.Sci.
Research Department of Epidemiology and Public Health (Frank, Batty, Kivimäki) and Research Department of Behavioural Science and Health (Frank, Cadar, Steptoe), University College London; Department of Psychology and Logopedics (Jokela) and Clinicum Unit (Kivimäki), Faculty of Medicine, University of Helsinki, Helsinki.

Notes

Send correspondence to Mr. Frank ([email protected]).

Competing Interests

All authors report no financial relationships with commercial interests.

Funding Information

Mr. Frank is supported by the Economic and Social Research Council (ESRC) and the Biotechnology and Sciences Research Council (BBSRC) (ES/P000347/1). Dr. Batty is supported by the U.K. Medical Research Council (MRC) (MR/P023444/1). Dr. Cadar is funded by the National Institute on Aging (grant RO1AG017644). Dr. Kivimäki has received grants from the Wellcome Trust (221854/Z/20/Z), NordForsk (75021), the MRC (K013351, S011676, R024227), the National Institute on Aging (R01AG056477), the Academy of Finland (329202), the Helsinki Institute of Life Science (H970), and the Finnish Work Environment Fund (190424).

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