Longitudinal association between depression and inflammatory markers: Results from the Netherlands Study of Depression and Anxiety

Femke Lamers, Yuri Milaneschi, Johannes H. Smit, Robert A. Schoevers, Gayle Wittenberg, Brenda W.J.H. Penninx

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: While cross-sectional associations of inflammatory markers interleukin-6 (IL-6) and C-reactive protein with major depressive disorder are well established, evidence for longitudinal associations mostly comes from studies on depression symptoms, not diagnoses. This study examined cross-sectional and bidirectional longitudinal associations between depression diagnosis and symptoms in an adult sample over a 6-year period. Methods: Data were obtained from the baseline (n = 2416) and 2- and 6-year follow-up assessments (n = 1925 and n = 1924, respectively) of the Netherlands Study of Depression and Anxiety. C-reactive protein and IL-6 were assessed at each wave, as were the Composite International Diagnostic Interview and Inventory of Depressive Symptomatology. Linear mixed models and generalized estimating equation models with a binomial distribution were used to study longitudinal associations between depression and inflammation and vice versa. Results: There was a consistent cross-sectional association between current depressive disorder (vs. no current disorder) and symptoms with IL-6 across all follow-up measurements (Cohen's d depression diagnosis = 0.06, p =.017; B standardized Inventory of Depressive Symptomatology = 0.029, SE = 0.011, p =.008). In longitudinal analyses, higher IL-6 levels predicted subsequent chronic course in those with a diagnosis at baseline in women but not in men (odds ratio women = 1.13, 95% confidence interval = 1.04–1.23), and both depressive disorder and high severity predicted higher IL-6 levels at the subsequent follow-up (p values <.01). In contrast, C-reactive protein was not associated with current depression in cross-sectional and longitudinal analyses. Conclusions: In this longitudinal study, cross-sectional and bidirectional longitudinal associations were found between depression and IL-6 levels. This underlines the importance of targeting inflammation pathways in the treatment of major depressive disorder. IL-6 could be a potential marker for patient profiling in personalized medicine approaches.

Original languageEnglish
Pages (from-to)829-837
Number of pages9
JournalBiological Psychiatry
Volume85
Issue number10
DOIs
Publication statusPublished - 15 May 2019

Cite this

@article{f70b20c81e524f9581aca459821fbf2c,
title = "Longitudinal association between depression and inflammatory markers: Results from the Netherlands Study of Depression and Anxiety",
abstract = "Background: While cross-sectional associations of inflammatory markers interleukin-6 (IL-6) and C-reactive protein with major depressive disorder are well established, evidence for longitudinal associations mostly comes from studies on depression symptoms, not diagnoses. This study examined cross-sectional and bidirectional longitudinal associations between depression diagnosis and symptoms in an adult sample over a 6-year period. Methods: Data were obtained from the baseline (n = 2416) and 2- and 6-year follow-up assessments (n = 1925 and n = 1924, respectively) of the Netherlands Study of Depression and Anxiety. C-reactive protein and IL-6 were assessed at each wave, as were the Composite International Diagnostic Interview and Inventory of Depressive Symptomatology. Linear mixed models and generalized estimating equation models with a binomial distribution were used to study longitudinal associations between depression and inflammation and vice versa. Results: There was a consistent cross-sectional association between current depressive disorder (vs. no current disorder) and symptoms with IL-6 across all follow-up measurements (Cohen's d depression diagnosis = 0.06, p =.017; B standardized Inventory of Depressive Symptomatology = 0.029, SE = 0.011, p =.008). In longitudinal analyses, higher IL-6 levels predicted subsequent chronic course in those with a diagnosis at baseline in women but not in men (odds ratio women = 1.13, 95{\%} confidence interval = 1.04–1.23), and both depressive disorder and high severity predicted higher IL-6 levels at the subsequent follow-up (p values <.01). In contrast, C-reactive protein was not associated with current depression in cross-sectional and longitudinal analyses. Conclusions: In this longitudinal study, cross-sectional and bidirectional longitudinal associations were found between depression and IL-6 levels. This underlines the importance of targeting inflammation pathways in the treatment of major depressive disorder. IL-6 could be a potential marker for patient profiling in personalized medicine approaches.",
keywords = "CRP, Depression severity, Depressive disorder, Epidemiology, IL-6, Longitudinal",
author = "Femke Lamers and Yuri Milaneschi and Smit, {Johannes H.} and Schoevers, {Robert A.} and Gayle Wittenberg and Penninx, {Brenda W.J.H.}",
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Longitudinal association between depression and inflammatory markers : Results from the Netherlands Study of Depression and Anxiety. / Lamers, Femke; Milaneschi, Yuri; Smit, Johannes H.; Schoevers, Robert A.; Wittenberg, Gayle; Penninx, Brenda W.J.H.

In: Biological Psychiatry, Vol. 85, No. 10, 15.05.2019, p. 829-837.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Longitudinal association between depression and inflammatory markers

T2 - Results from the Netherlands Study of Depression and Anxiety

AU - Lamers, Femke

AU - Milaneschi, Yuri

AU - Smit, Johannes H.

AU - Schoevers, Robert A.

AU - Wittenberg, Gayle

AU - Penninx, Brenda W.J.H.

PY - 2019/5/15

Y1 - 2019/5/15

N2 - Background: While cross-sectional associations of inflammatory markers interleukin-6 (IL-6) and C-reactive protein with major depressive disorder are well established, evidence for longitudinal associations mostly comes from studies on depression symptoms, not diagnoses. This study examined cross-sectional and bidirectional longitudinal associations between depression diagnosis and symptoms in an adult sample over a 6-year period. Methods: Data were obtained from the baseline (n = 2416) and 2- and 6-year follow-up assessments (n = 1925 and n = 1924, respectively) of the Netherlands Study of Depression and Anxiety. C-reactive protein and IL-6 were assessed at each wave, as were the Composite International Diagnostic Interview and Inventory of Depressive Symptomatology. Linear mixed models and generalized estimating equation models with a binomial distribution were used to study longitudinal associations between depression and inflammation and vice versa. Results: There was a consistent cross-sectional association between current depressive disorder (vs. no current disorder) and symptoms with IL-6 across all follow-up measurements (Cohen's d depression diagnosis = 0.06, p =.017; B standardized Inventory of Depressive Symptomatology = 0.029, SE = 0.011, p =.008). In longitudinal analyses, higher IL-6 levels predicted subsequent chronic course in those with a diagnosis at baseline in women but not in men (odds ratio women = 1.13, 95% confidence interval = 1.04–1.23), and both depressive disorder and high severity predicted higher IL-6 levels at the subsequent follow-up (p values <.01). In contrast, C-reactive protein was not associated with current depression in cross-sectional and longitudinal analyses. Conclusions: In this longitudinal study, cross-sectional and bidirectional longitudinal associations were found between depression and IL-6 levels. This underlines the importance of targeting inflammation pathways in the treatment of major depressive disorder. IL-6 could be a potential marker for patient profiling in personalized medicine approaches.

AB - Background: While cross-sectional associations of inflammatory markers interleukin-6 (IL-6) and C-reactive protein with major depressive disorder are well established, evidence for longitudinal associations mostly comes from studies on depression symptoms, not diagnoses. This study examined cross-sectional and bidirectional longitudinal associations between depression diagnosis and symptoms in an adult sample over a 6-year period. Methods: Data were obtained from the baseline (n = 2416) and 2- and 6-year follow-up assessments (n = 1925 and n = 1924, respectively) of the Netherlands Study of Depression and Anxiety. C-reactive protein and IL-6 were assessed at each wave, as were the Composite International Diagnostic Interview and Inventory of Depressive Symptomatology. Linear mixed models and generalized estimating equation models with a binomial distribution were used to study longitudinal associations between depression and inflammation and vice versa. Results: There was a consistent cross-sectional association between current depressive disorder (vs. no current disorder) and symptoms with IL-6 across all follow-up measurements (Cohen's d depression diagnosis = 0.06, p =.017; B standardized Inventory of Depressive Symptomatology = 0.029, SE = 0.011, p =.008). In longitudinal analyses, higher IL-6 levels predicted subsequent chronic course in those with a diagnosis at baseline in women but not in men (odds ratio women = 1.13, 95% confidence interval = 1.04–1.23), and both depressive disorder and high severity predicted higher IL-6 levels at the subsequent follow-up (p values <.01). In contrast, C-reactive protein was not associated with current depression in cross-sectional and longitudinal analyses. Conclusions: In this longitudinal study, cross-sectional and bidirectional longitudinal associations were found between depression and IL-6 levels. This underlines the importance of targeting inflammation pathways in the treatment of major depressive disorder. IL-6 could be a potential marker for patient profiling in personalized medicine approaches.

KW - CRP

KW - Depression severity

KW - Depressive disorder

KW - Epidemiology

KW - IL-6

KW - Longitudinal

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U2 - 10.1016/j.biopsych.2018.12.020

DO - 10.1016/j.biopsych.2018.12.020

M3 - Article

VL - 85

SP - 829

EP - 837

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

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