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

Föcking, Melanie, Sabherwal, Sophie, Cates, Hannah M., Scaife, Caitriona, Dicker, Patrick, Hryniewiecka, Magdalena, Wynne, Kieran, Rutten, Bart P. F., Lewis, Glyn, Cannon, Mary, Nestler, Eric J., Heurich-Sevcenco, Meike ORCID: https://orcid.org/0000-0003-0105-2702, Cagney, Gerard, Zammit, Stanley ORCID: https://orcid.org/0000-0002-2647-9211 and Cotter, David R. 2019. 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 26 , pp. 524-533. 10.1038/s41380-018-0306-z

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Abstract

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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Pharmacy Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Additional Information:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
Publisher:	Springer Nature
ISSN:	1359-4184
Date of First Compliant Deposit:	11 January 2019
Date of Acceptance:	30 October 2018
Last Modified:	02 May 2023 16:04
URI:	https://orca.cardiff.ac.uk/id/eprint/118307

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