How variants in inflammatory mediator genes influence symptom severity of psychiatric disorders: Findings from the PsyCourse study

Abstract

Alterations in glial cell function and cytokine levels in the central nervous system may be influenced by neuroinflammatory processes, which have a pathogenic role in psychiatric disorders. Variability in genes that encode inflammatory mediators is associated with risk of developing mental disorders. Therefore, by analyzing data from the transdiagnostic PsyCourse Study, we aimed to investigate whether variations in inflammatory mediator genes are associated with current symptom severity. We used cross-sectional data from 1320 individuals with a psychiatric disorder and 466 neurotypical individuals. Outcome variables were the psychopathological data from various rating scales and questionnaires that measured depressive, psychotic, and manic symptoms. Furthermore, from a whole-genome SNP array dataset, we extracted single nucleotide polymorphisms (SNPs) in the loci of genes related to inflammatory mediators, and we performed an association analysis by considering covariates. False discovery rate (FDR) was used to adjust the results for multiple comparisons. A total of 1594 individuals and 1336 SNPs were included in the analyses. The results of regression analysis showed a significant positive association of six SNPs located on the interleukin (IL)-1 receptor type 1 (IL-1R1) gene locus with Altman Self-Rating Mania Scale scores (FDR-adjusted p value < 0.05). Our findings show that genetic variations in IL-1R1 may influence the pathophysiology of psychiatric disorders by affecting brain cytokine profiles associated with manic episodes. IL-1R1 encodes a membrane-bound receptor for IL-1. Several physiological functions, including inflammation, are linked to the IL-1/IL-1R1 signaling pathway. Replication of our findings is warranted.

Keywords: IL-1/IL-1R1 signaling; Mania; Neuroinflammation.