Complement system biomarkers in first episode psychosis

SCHIZOPHRENIA RESEARCH

卷:204

Article

Kopczynska, Maja¹  Zelek, Wioleta¹  Touchard, Samuel¹  Gaughran, Fiona³  Di Forti, Marta³  Mondelli, Valeria³  Murray, Robin³  O'Donovan, Michael C.²  Morgan, B. Paul¹ 

[1] Cardiff Univ, Syst Immun Univ Res Inst, Cardiff CF144XN, S Glam, Wales

[2] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Sch Med, Cardiff CF144XN, S Glam, Wales

[3] Kings Coll London, Inst Psychiat Psychol & Neurosci, De Crespigny Pk, London SE5 8AF, England

关键词: Complement;    Inflammation;    Biomarkers;    Predictors;   

DOI  :  10.1016/j.schres.2017.12.012

来源: Elsevier

【 摘 要 】

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 explored whether complement dysregulation occurred in first episode psychosis (FEP) and whether this provides a source of biomarkers. Eleven complement analytes (C1q, C3, C4, C5, factor B [FB], terminal complement complex [TCC], factor H [FM, FH-related proteins [FHR125], Properdin, Cl inhibitor [Clinh], soluble complement receptor 1 [CRI ]) 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. When measured 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 final model included demographics (sex, ethnicity, age, tobacco smoking) and a subset of analytes (C3, C4, C5, TCC, C1 inh, 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 therapeutic modification of the inflammatory response. (C) 2018 The Authors. Published by Elsevier B.V.

【 授权许可】

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