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Complement system biomarkers in first episode psychosis

Kopczynska, Maja, Zelek, Wioleta, Touchard, Samuel, Gaughran, Fiona, Di Forti, Marta, Mondelli, Valeria, Murray, Robin, O'Donovan, Michael and Morgan, B. Paul 2019. Complement system biomarkers in first episode psychosis. Schizophrenia Research 204 , pp. 16-22. 10.1016/j.schres.2017.12.012

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Abstract

Several lines of evidence implicate immunological/inflammatory factors in development of schizophrenia. Complement is a key driver of inflammation, and complement dysregulation causes pathology in many diseases. Here we exploredwhether complement dysregulation occurred in first episode psychosis (FEP) andwhether this provides a source of biomarkers. Eleven complement analytes (C1q, C3, C4, C5, factor B [FB], terminal complement complex [TCC], factor H [FH], FH-related proteins [FHR125], Properdin, C1 inhibitor [C1inh], soluble complement receptor 1 [CR1]) plus C-reactive protein (CRP) were measured in serum from 136 first episode psychosis (FEP) cases and 42 mentally healthy controls using established in-house or commercial ELISA. The relationship between caseness and variables (analytes measured, sex, age, ethnicity, tobacco/cannabis smoking) was tested by multivariate logistic regression. Whenmeasured individually, only TCC was significantly different between FEP and controls (p=0.01). Stepwise selection demonstrated interdependence between some variables and revealed other variables that significantly and independently contributed to distinguishing cases and controls. The finalmodel included demographics (sex, ethnicity, age, tobacco smoking) and a subset of analytes (C3, C4, C5, TCC, C1inh, FHR125, CR1). A receiver operating curve analysis combining these variables yielded an area under the curve of 0.79 for differentiating FEP from controls. This model was confirmed by multiple replications using randomly selected sample subsets. The data suggest that complement dysregulation occurs in FEP, supporting an underlying immune/inflammatory component to the disorder. Classification of FEP cases according to biological variables rather than symptoms would help stratify cases to identify those that might most benefit from therapeuticmodification of the inflammatory response.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Elsevier
ISSN: 0920-9964
Funders: Wellcome Trust
Date of First Compliant Deposit: 5 February 2018
Date of Acceptance: 22 December 2017
Last Modified: 10 Apr 2019 10:30
URI: http://orca.cf.ac.uk/id/eprint/108833

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