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. 2023 Jul 4;49(4):893-902.
doi: 10.1093/schbul/sbac201.

Association of Complement and Coagulation Pathway Proteins With Treatment Response in First-Episode Psychosis: A Longitudinal Analysis of the OPTiMiSE Clinical Trial

Subash Raj Susai  1 , Melanie Föcking  1 , David Mongan  1 , Meike Heurich  2 , Fiona Coutts  3 , Alice Egerton  3 , Tony Whetton  4 , Inge Winter-van Rossum  5 , Richard D Unwin  6 , Thomas A Pollak  7 , Mark Weiser  8   9 , Marion Leboyer  10 , Dan Rujescu  11   12 , Jonah F Byrne  1 , George W Gifford  3 , Paola Dazzan  3 , Nikolaos Koutsouleris  7   12 , René S Kahn  13 , David R Cotter  1 , Philip McGuire  3
Affiliations

Association of Complement and Coagulation Pathway Proteins With Treatment Response in First-Episode Psychosis: A Longitudinal Analysis of the OPTiMiSE Clinical Trial

Subash Raj Susai et al. Schizophr Bull. .

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 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.

Keywords: Schizophrenia; antipsychotic agents; biomarkers; complement system proteins; immune markers; psychotic disorder.

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Figures

Fig. 1.
Fig. 1.
Group difference in pre-treatment complement C4A levels between patients who were in remission, or not in remission after 4 weeks of treatment with amisulpride.
Fig. 2.
Fig. 2.
Schematic representation of complement cascade proteins dysregulated at baseline in participants with a poor symptomatic response to treatment Created with BioRender.com.
See this image and copyright information in PMC

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