Transdiagnostic inflammatory subgroups among psychiatric disorders and their relevance to role functioning: a nested case-control study of the ALSPAC cohort
Individuals with psychotic disorders and depressive disorder exhibit altered concentrations of peripheral inflammatory markers. It has been suggested that clinical trials of anti-inflammatory therapies for psychiatric disorders should stratify patients by their inflammatory profile. Hence, we investigated whether different subgroups of individuals exist across psychiatric disorders, based on their inflammatory biomarker signatures. We measured the plasma concentrations of 17 inflammatory markers and receptors in 380 participants with psychotic disorder, depressive disorder or generalised anxiety disorder and 399 controls without psychiatric symptoms from the ALSPAC cohort at age 24. We employed a semi-supervised clustering algorithm, which discriminates multiple clusters of psychiatric disorder cases from controls. The best fit was for a two-cluster model of participants with psychiatric disorders (Adjusted Rand Index (ARI) = 0.52 ± 0.01) based on the inflammatory markers. Permutation analysis indicated the stability of the clustering solution performed better than chance (ARI = 0.43 ± 0.11; p < 0.001), and the clusters explained the inflammatory marker data better than a Gaussian distribution (p = 0.021). Cluster 2 exhibited marked increases in sTNFR1/2, suPAR, sCD93 and sIL-2RA, compared to cluster 1. Participants in the cluster exhibiting higher inflammation were less likely to be in employment, education or training, indicating poorer role functioning. This study found evidence for a novel pattern of inflammatory markers specific to psychiatric disorders and strongly associated with a transdiagnostic measure of illness severity. sTNFR1/2, suPAR, sCD93 and sIL-2RA could be used to stratify clinical trials of anti-inflammatory therapies for psychiatric disorders.
The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z)
University of Bristol provide core support for ALSPAC
Medical Research Council, including grant numbers MR/L022206/1 and MR/M006727/1
Wellcome Flagship Innovations Award (IMPETUS - 220438Z/20/Z)
Health Research Board Investigator Led Project Grant (ILP-POR2017-039)
European Research Council Consolidator Award (iHEAR 724809)
Health Research Board Investigator Led Project Grant (ILPPHR-2019-009)
Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z)
Health Service Executive National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland.
Health Research Board (HRB) under grant number HRB/ HRA/PHR/2015-1293
Science Foundation Ireland (SFI) under Grant Number 16/RC/3948
European Regional Development Fund and FutureNeuro industry partners
NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol
A comprehensive list of grants funding is available on the ALSPAC website
CommentsThe original article is available at https://www.nature.com/
Published CitationByrne JF. et al. Transdiagnostic inflammatory subgroups among psychiatric disorders and their relevance to role functioning: a nested case-control study of the ALSPAC cohort. Transl Psychiatry. 2022;12(1):377.
Publication Date9 September 2022
- Beaumont Hospital
- FutureNeuro Centre
PublisherNature Pub. Group
- Published Version (Version of Record)