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Title: Complement proteins are elevated in blood serum but not CSF in clinical high-risk and antipsychotic-naïve first-episode psychosis.
Austin Authors: Cropley, V L;Kittel, M;Heurich, M;Föcking, M;Leweke, F M;Pantelis, C
Affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & NorthWestern Mental Health, Melbourne, Australia.
Institute for Clinical Chemistry, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
School of Pharmacy and Pharmaceutical Sciences, College of Biomedical and Life Sciences, Cardiff University, United Kingdom.
Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
Brain and Mind Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
The Florey Institute of Neuroscience and Mental Health
Issue Date: Oct-2023
Date: 2023
Publication information: Brain, Behavior, and Immunity 2023-10; 113
Abstract: Alterations in the complement system have been reported in some people with psychotic disorder, including in pre-psychotic individuals, suggesting that complement pathway dysregulation may be a feature of the early psychosis phenotype. Measurement of complement protein expression in psychosis has been largely restricted to the blood from patients with established illness who were taking antipsychotic medication. The present study examined a range of complement proteins in blood and cerebrospinal fluid (CSF) derived from individuals at clinical high-risk for psychosis (CHR), antipsychotic-naïve first-episode psychosis (FEP) and healthy controls. A panel of complement proteins (C1q, C3, C3b/iC3b, C4, factor B and factor H) were quantified in serum and matched CSF in 72 participants [n = 23 individuals at CHR, n = 24 antipsychotic-naïve FEP, n = 25 healthy controls] using a multiplex immunoassay. Analysis of covariance was used to assess between-group differences in complement protein levels in serum and CSF. Pearson's correlation was used to assess the relationship between serum and CSF proteins, and between complement proteins and symptom severity. In serum, all proteins, except for C3, were significantly higher in FEP and CHR. While a trend was observed, protein levels in CSF did not statistically differ between groups and appeared to be impacted by BMI and sample storage time. Across the whole sample, serum and CSF protein levels were not correlated. In FEP, higher levels of serum classical and alternative grouped pathway components were correlated with symptom severity. Our exploratory study provides evidence for increased activity of the peripheral complement system in the psychosis spectrum, with such elevations varying with clinical severity. Further study of complement in CSF is warranted. Longitudinal investigations are required to elucidate whether complement proteins change peripherally and/or centrally with progression of psychotic illness.
DOI: 10.1016/j.bbi.2023.07.004
Journal: Brain, Behavior, and Immunity
Start page: 136
End page: 144
PubMed URL: 37437819
ISSN: 1090-2139
Type: Journal Article
Subjects: Biomarker
Cerebrospinal fluid
Antipsychotic Agents/therapeutic use
Appears in Collections:Journal articles

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