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Evidence that complement and coagulation proteins are mediating the clinical response to omega-3 fatty acids: A mass spectrometry-based investigation in subjects at clinical high-risk for psychosis

Version 2 2024-06-19, 16:15
Version 1 2023-02-10, 02:47
journal contribution
posted on 2024-06-19, 16:15 authored by SR Susai, C Healy, D Mongan, M Heurich, JF Byrne, M Cannon, G Cagney, K Wynne, C Markulev, MR Schäfer, M Berger, N Mossaheb, M Schlögelhofer, S Smesny, IB Hickie, GE Berger, EYH Chen, L de Haan, DH Nieman, M Nordentoft, A Riecher-Rössler, S Verma, R Street, A Thompson, Alison YungAlison Yung, B Nelson, PD McGorry, M Föcking, GP Amminger, D Cotter
AbstractPreliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins.



Translational Psychiatry



Article number

ARTN 454


United States







Publication classification

C1 Refereed article in a scholarly journal