Association of Complement and Coagulation Pathway Proteins With Treatment Response in First-Episode Psychosis: A Longitudinal Analysis of the OPTiMiSE Clinical Trial
Susai, Subash Raj; Föcking, Melanie; Mongan, David; Heurich, Meike; Coutts, Fiona; Egerton, Alice; Whetton, Tony; Winter-van Rossum, Inge; Unwin, Richard D; Pollak, Thomas A; Weiser, Mark; Leboyer, Marion; Rujescu, Dan; Byrne, Jonah F; Gifford, George W; Dazzan, Paola; Koutsouleris, Nikolaos; Kahn, René S; Cotter, David R; McGuire, Philip
(2023) Schizophrenia bulletin, volume 49, issue 4, pp. 893 - 902
(Article)
Abstract
BACKGROUND AND HYPOTHESIS: Treatment response to specific antipsychotic medications is difficult to predict on clinical grounds alone. The current study hypothesizes that the baseline complement pathway activity predicts the treatment response and investigates the relationship between baseline plasma biomarkers with treatment response to antipsychotic medications. STUDY DESIGN: Baseline plasma samples
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were collected from first episode of psychosis patients (n = 243) from a multi-center clinical trial. The participants were treated with amisulpride for 4 weeks. Levels of complement and coagulation proteins at baseline were measured using both data-dependent and data-independent mass spectrometry approaches. The primary outcome was remission status at 4 weeks and the secondary outcomes included change in psychotic and functional symptoms over the period of treatment. In addition, immunoassays were performed at baseline for complement C1R, as well as for activation markers C4a and sC5b-9. STUDY RESULTS: The plasma level of complement variant C4A was significantly associated with remission at 4 weeks. Moreover, higher levels of several complement and coagulation pathway proteins were associated with a reduction in psychotic symptoms and an improvement in functioning. Immunoassays showed an association of baseline levels of C1R and C4a as well as complement activation marker sC5b-9 levels with treatment response. CONCLUSION: The results demonstrated that the response to antipsychotic treatment might be related to pre-treatment levels of plasma complement and coagulation pathway proteins. This is consistent with independent evidence associating immune dysfunction with the pathophysiology of psychosis. Moreover, these results inform the development of novel therapeutic approaches that target the complement system for psychosis.
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Keywords: Schizophrenia, antipsychotic agents, biomarkers, complement system proteins, immune markers, psychotic disorder, Psychiatry and Mental health
ISSN: 0586-7614
Publisher: Oxford University Press
Note: Funding Information: The OPTiMiSE clinical trial was funded by European Commission within the 7th Program (HEALTH-F2-2010-242114). The research work was funded also by Irish Health Research Board grant to David Cotter (HRB-ILP-2019-005), Wellcome Trust IMPETUS Innovations Flagship grant (project 220438Z/20/Z) D.M. is a Fellow on the Irish Clinical Academic Training (ICAT) Programme which is supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland. S.R.S is supported by the Health Research Board (HRB) under grant number HRB/HRA/PHR/2015-1293. D.R.C and J.F.B are supported in part by Science Foundation Ireland (SFI) under Grant Number 16/RC/3948 and co-funded under the European Regional Development Fund and by FutureNeuro industry partners. Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
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