Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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, Cagney, Gerard, Zammit, Stanley 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 , -. 10.1038/s41380-018-0306-z

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (746kB) | Preview

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: Publication
Status: In Press
Schools: Pharmacy
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
ISSN: 1359-4184
Date of First Compliant Deposit: 11 January 2019
Date of Acceptance: 30 October 2018
Last Modified: 14 Jan 2019 12:15
URI: http://orca.cf.ac.uk/id/eprint/118307

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics