Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts
Year: 2021
Type: article
Abstract: We examined whether inflammation is uniformly associated with all depressive and anxiety symptoms, and whether these associations are potentially causal. Data was from 147,478 individuals from the UK Biobank (UKB) and 2,905 from the Netherlands Study of Depression and Anxiety (NESDA). Circulating C-reactive protein (CRP) was measured in both cohorts and interleukin-6 (IL-6) in NESDA. Genetic instruments for these proteins were obtained from published GWAS and UKB. Depressive and anxiety symptoms were assessed with self-report questionnaires. In NESDA, neurovegetative (appetite, sleep, psychomotor) symptoms were disaggregated as increased vs. decreased. In joint analyses, higher CRP was associated with depressive symptoms of depressed mood (OR = 1.06, 95% CI = 1.05-1.08), altered appetite (OR = 1.25, 95%CI = 1.23-1.28), sleep problems (OR = 1.05, 95%CI = 1.04-1.06), and fatigue (OR = 1.12, 95% CI = 1.11-1.14), and with anxiety symptoms of irritability (OR = 1.06, 95% CI = 1.05-1.08) and worrying control (OR = 1.03, 95% CI = 1.02-1.04). In NESDA, higher IL-6 was additionally associated with anhedonia (OR = 1.30, 95% CI = 1.12-1.52). Higher levels of both CRP (OR = 1.27, 95% CI = 1.13-1.43) and IL-6 (OR = 1.26, 95% CI = 1.07-1.49) were associated with increased sleep. Higher CRP was associated with increased appetite (OR = 1.21, 95% CI = 1.08-1.35) while higher IL-6 with decreased appetite (OR = 1.45, 95% CI = 1.18-1.79). In Mendelian Randomisation analyses, genetically predicted higher IL-6 activity was associated with increased risk of fatigue (estimate = 0.25, SE = 0.08) and sleep problems (estimate = 0.19, SE = 0.07). Inflammation was associated with core depressive symptoms of low mood and anhedonia and somatic/neurovegetative symptoms of fatigue, altered sleep and appetite changes. Less consistent associations were found for anxiety. The IL-6/IL-6R pathway could be causally linked to depression. Experimental studies are required to further evaluate causality, mechanisms, and usefulness of immunotherapies for depressive symptoms.
Source: Molecular Psychiatry
Institutions: Amsterdam Neuroscience, Amsterdam Public Health, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Max Planck Institute of Psychiatry, University of Cambridge, Cambridgeshire and Peterborough NHS Foundation Trust, MRC Biostatistics Unit, University of Bristol, MRC Integrative Epidemiology Unit
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
Funders: Wellcome Trust, MQ: Transforming Mental Health, International Max Planck Research School for Environmental, Cellular and Molecular Microbiology, National Institute for Health and Care Research, British Heart Foundation, European Commission, Cambridge University Hospitals, BMA Foundation for Medical Research, International Max Planck Research School for Advanced Methods in Process and Systems Engineering, Amsterdam Neuroscience, Medical Research Council
Awards: Genetics and causality: towards more accessible and more reliable Mendelian randomization investigations, NIHR Senior Investigator Award, G1927824909, Psychosis Immune Mechanism Stratified Medicine Study (PIMS), Large-scale integrative genomic studies of high-dimensional traits in cardiovascular diseases (renewal), G2474488143, G4260143917, G5189661712, G5702265173, G5850737185, G6342754709, G6848567189, Inflammation and Immunity in Depression: from novel mechanisms towards therapeutics, G710448223, The BHF Chair of Epidemiology and Medicine, G7331652800, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application (renewal). (Joint funding with MRC), G8201205252, MICA: Mental Health Data Pathfinder: University of Cambridge, Cambridgeshire & Peterborough NHS Foundation Trust, and Microsoft, Bringing the field of psychiatry forward: Unraveling heterogeneity of Depression
OpenAlex ID: W3167458657