Complement pathway changes at age 12 are associated with psychotic experiences at age 18 in a longitudinal population-based study: evidence for a role of stress.
journal contributionposted on 12.03.2021, 14:48 by Melanie Focking, Sophie Sabherwal, Hannah M Cates, Caitriona Scaife, Patrick Dicker, Magdalena Hryniewiecka, Kieran Wynne, Bart PF Rutten, Glyn Lewis, Mary Cannon, Eric J Nestler, Meike Heurich, Gerard Cagney, Stanley Zammit, David Cotter
The complement cascade is a major component of the immune defence against infection, and there is increasing evidence for a role of dysregulated complement in major psychiatric disorders. We undertook a directed proteomic analysis of the complement signalling pathway (n = 29 proteins) using data-independent acquisition. Participants were recruited from the UK avon longitudinal study of parents and children (ALSPAC) cohort who participated in psychiatric assessment interviews at ages 12 and 18. Protein expression levels at age 12 among individuals who reported psychotic experiences (PEs) at age 18 (n = 64) were compared with age-matched controls (n = 67). Six out of the 29 targeted complement proteins or protein subcomponents were significantly upregulated following correction for multiple comparisons (VTN↑, C1RL↑, C8B↑, C8A↑, CFH↑, and C5↑). We then undertook an unbiased plasma proteomic analysis of mice exposed to chronic social stress and observed dysregulation of 11 complement proteins, including three that were altered in the same direction in individuals with PE (C1R↑, CFH↑, and C5↑). Our findings indicate that dysregulation of the complement protein pathway in blood is associated with incidence of psychotic experiences and that these changes may reflect exposure to stress.
The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2)
European Research Council Consolidator Award (Grant Ref: 724809 iHEAR)
Irish Health Research Board through a Clinician Scientist Award
University of Bristol (ALSPAC)
NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust
CommentsThe original article is available at https://www.nature.com/
Published CitationFöcking M, Sabherwal S, Cates HM, Scaife C, Dicker P, Hryniewiecka M, Wynne K, Rutten BPF, Lewis G, Cannon M, Nestler EJ, Heurich M, Cagney G, Zammit S, Cotter DR. Complement pathway changes at age 12 are associated with psychotic experiences at age 18 in a longitudinal population-based study: evidence for a role of stress. Molecular Psychiatry. 2021;26(2):524-533.
Publication Date11 January 2019
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- Published Version (Version of Record)