Role of inflammation in depression and anxiety: Tests for disorder specificity, linearity and potential causality of association in the UK Biobank

被引：40

作者：

Ye, Zheng ^{[1
]}

Kappelmann, Nils ^{[2
,3
]}

Moser, Sylvain ^{[2
,3
]}

Smith, George Davey ^{[4
,5
]}

Burgess, Stephen ^{[6
,7
]}

Jones, Peter B. ^{[1
,8
]}

Khandaker, Golam M. ^{[1
,4
,5
,8
,9
]}

机构：

[1] Univ Cambridge, Dept Psychiat, Cambridge, England

[2] Max Planck Inst Psychiat, Dept Res Translat Psychiat, Munich, Germany

[3] Int Max Planck Res Sch Translat Psychiat IMPRS TP, Munich, Germany

[4] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England

[5] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England

[6] Univ Cambridge, MRC Biostat Unit, Cambridge, England

[7] Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England

[8] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England

[9] Univ Bristol, Ctr Acad Mental Hlth, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England

来源：

ECLINICALMEDICINE | 2021年 / 38卷

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

Depression; Anxiety; Inflammation; CRP; Il-6; Mendelian randomisation; C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; MENDELIAN RANDOMIZATION; INTERLEUKIN-6; RECEPTOR; CIRCULATING LEVELS; METAANALYSIS; HEALTH; IL-6; SCHIZOPHRENIA; CYTOKINE;

D O I：

10.1016/j.eclinm.2021.100992

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Concentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and other inflammatory markers are elevated in people with depression and anxiety compared to controls, but evidence for disorder-specificity, linearity and potential causality is sparse. Methods: Using population-based data from up to 144,890 UK Biobank cohort participants, we tested associations of circulating CRP concentrations with depression and anxiety symptom scores and probable diagnosis, including tests for linearity, disorder-specificity and sex difference. We examined potential causality using 1-sample and 2-sample Mendelian randomisation (MR) analyses testing associations of genetically-predicted CRP concentration and IL-6 activity with depression and anxiety. The study was conducted from June 2019 to February 2021. Findings: CRP concentration was associated with depressive and anxiety symptom scores and with probable diagnoses of depression and generalised anxiety disorder (GAD) in a dose-response fashion. These associations were stronger for depression than for anxiety, and for women than for men although less consistently. MR analyses provided consistent results suggesting that genetically predicted higher IL-6 activity was associated with increased risk for depressive symptoms, while genetically-predicted higher CRP concentration was associated with decreased risks of depressive and anxiety symptoms. Interpretation: Altered activity of the IL-6/IL-6R pathway could be a risk factor for depression. The field now requires experimental studies of IL-6 modulation in humans and animal models to further examine causality, mechanisms and treatment potential. Such studies are also needed to elucidate mechanisms for divergent associations of genetically-predicted higher IL-6 activity (risk increasing) and higher CRP concentrations (protective) with depression/anxiety. (C) 2021 The Authors. Published by Elsevier Ltd.

引用

页数：9

共 54 条

[1]

[Anonymous], 2013, DIAGNOSTIC STAT MANU

[2]

Burgess Stephen, 2019, Wellcome Open Res, V4, P186, DOI 10.12688/wellcomeopenres.15555.3

[3] Systematic review and meta-analysis of the association between peripheral inflammatory cytokines and generalised anxiety disorder [J].