Abstract
Highlights
•Low-grade inflammation may occur in association with several mental disorders of early adulthood, but associations with novel markers of chronic inflammation such as soluble urokinase plasminogen activator receptor (suPAR) are less well-established.
•We measured levels of 10 plasma inflammatory markers (IFN-γ, IL-6, IL-8, IL-10, TNF-α, CRP, sVCAM1, sICAM1, suPAR and alpha-2-macroglobulin) in 781 participants in the Avon Longitudinal Study of Parents and Children at age 24.
•We found evidence for higher levels of IL-6 and suPAR in 24-year-olds with psychotic disorder compared to controls, with weaker evidence for higher levels of suPAR in individuals with depressive disorder compared to controls.
•In secondary analyses we found preliminary evidence that plasma suPAR levels were associated with psychiatric co-morbidity.
Abstract
Background: Low-grade inflammation may occur in association with several mental disorders of early adulthood, though associations with markers of chronic inflammation such as soluble urokinase plasminogen activator receptor (suPAR) are less well-established. We aimed to examine associations between acute and chronic inflammatory markers and mental disorders, as well as psychiatric co-morbidity, in young adults aged 24 years in the Avon Longitudinal Study of Parents and Children.
Methods: Included were 781 participants (of 4019 who attended at age 24 years) who completed psychiatric assessments and provided plasma samples. Of these, 377 met criteria for psychotic disorder, depressive disorder or generalised anxiety disorder and 404 did not. Plasma concentrations of IFN-γ, IL-6, IL-8, IL-10, TNF-α, CRP, sVCAM1, sICAM1, suPAR and alpha-2-macroglobulin were measured using immunoassays. Logistic regression compared standardised inflammatory marker levels in cases and controls. Negative binomial regression evaluated associations between inflammatory markers and co-morbidity (number of mental disorders). Models were adjusted for sex, body mass index, cigarette smoking, cannabis use and employment status, then additionally for childhood trauma.
Results: For psychotic disorder, there was evidence for associations with IL-6 (odds ratio[OR] 1.68, 95%CI 1.20–2.34) and suPAR (OR 1.74, 95%CI 1.17–2.58). There was weaker evidence for an association between suPAR and depressive disorder (OR 1.31, 95%CI 1.05–1.62). There was little evidence for associations between inflammatory markers and generalised anxiety disorder. There was weak evidence for an association between suPAR and co-morbidity (β 0.10, 95%CI 0.01–0.19). There was little evidence for additional confounding by childhood trauma.
Conclusions: There was evidence that 24-year-olds with psychotic disorder had raised plasma IL-6 and suPAR concentrations compared to controls. These findings have implications regarding the role of inflammation in mental disorders in early adulthood.
•Low-grade inflammation may occur in association with several mental disorders of early adulthood, but associations with novel markers of chronic inflammation such as soluble urokinase plasminogen activator receptor (suPAR) are less well-established.
•We measured levels of 10 plasma inflammatory markers (IFN-γ, IL-6, IL-8, IL-10, TNF-α, CRP, sVCAM1, sICAM1, suPAR and alpha-2-macroglobulin) in 781 participants in the Avon Longitudinal Study of Parents and Children at age 24.
•We found evidence for higher levels of IL-6 and suPAR in 24-year-olds with psychotic disorder compared to controls, with weaker evidence for higher levels of suPAR in individuals with depressive disorder compared to controls.
•In secondary analyses we found preliminary evidence that plasma suPAR levels were associated with psychiatric co-morbidity.
Abstract
Background: Low-grade inflammation may occur in association with several mental disorders of early adulthood, though associations with markers of chronic inflammation such as soluble urokinase plasminogen activator receptor (suPAR) are less well-established. We aimed to examine associations between acute and chronic inflammatory markers and mental disorders, as well as psychiatric co-morbidity, in young adults aged 24 years in the Avon Longitudinal Study of Parents and Children.
Methods: Included were 781 participants (of 4019 who attended at age 24 years) who completed psychiatric assessments and provided plasma samples. Of these, 377 met criteria for psychotic disorder, depressive disorder or generalised anxiety disorder and 404 did not. Plasma concentrations of IFN-γ, IL-6, IL-8, IL-10, TNF-α, CRP, sVCAM1, sICAM1, suPAR and alpha-2-macroglobulin were measured using immunoassays. Logistic regression compared standardised inflammatory marker levels in cases and controls. Negative binomial regression evaluated associations between inflammatory markers and co-morbidity (number of mental disorders). Models were adjusted for sex, body mass index, cigarette smoking, cannabis use and employment status, then additionally for childhood trauma.
Results: For psychotic disorder, there was evidence for associations with IL-6 (odds ratio[OR] 1.68, 95%CI 1.20–2.34) and suPAR (OR 1.74, 95%CI 1.17–2.58). There was weaker evidence for an association between suPAR and depressive disorder (OR 1.31, 95%CI 1.05–1.62). There was little evidence for associations between inflammatory markers and generalised anxiety disorder. There was weak evidence for an association between suPAR and co-morbidity (β 0.10, 95%CI 0.01–0.19). There was little evidence for additional confounding by childhood trauma.
Conclusions: There was evidence that 24-year-olds with psychotic disorder had raised plasma IL-6 and suPAR concentrations compared to controls. These findings have implications regarding the role of inflammation in mental disorders in early adulthood.
| Original language | English |
|---|---|
| Pages (from-to) | 90-100 |
| Number of pages | 11 |
| Journal | Brain, Behavior, and Immunity |
| Volume | 111 |
| Early online date | 31 Mar 2023 |
| DOIs | |
| Publication status | E-pub ahead of print - 31 Mar 2023 |
Bibliographical note
Funding Information:DM is a Fellow on the Irish Clinical Academic Training (ICAT) Programme which is supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland. MC is supported by a European Research Council Consolidator Award (iHEAR 724809). DC s funded by a Wellcome Trust Innovations Award, number 220438Z/20/Z, in part by a research grant from Science Foundation Ireland (SFI) under Grant Number 16/RC/3948415 and co-funded under the European Regional Development Fund and by FutureNeuro industry partners. JFB is supported by a Wellcome Flagship Innovations Award (220438Z/20/Z). SZ is supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The UK Medical Research Council and Wellcome Trust (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and David Mongan will serve as guarantor for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). Data collection for outcomes data used in this research was funded by the Medical Research Council (MR/M006727/1 and MR/L022206/1) and Wellcome Trust (08426812/Z/07/Z). The funders had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
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