Translational Psychiatry (Oct 2022)

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

  • Subash Raj Susai,
  • Colm Healy,
  • David Mongan,
  • Meike Heurich,
  • Jonah F. Byrne,
  • Mary Cannon,
  • Gerard Cagney,
  • Kieran Wynne,
  • Connie Markulev,
  • Miriam R. Schäfer,
  • Maximus Berger,
  • Nilufar Mossaheb,
  • Monika Schlögelhofer,
  • Stefan Smesny,
  • Ian B. Hickie,
  • Gregor E. Berger,
  • Eric Y. H. Chen,
  • Lieuwe de Haan,
  • Dorien H. Nieman,
  • Merete Nordentoft,
  • Anita Riecher-Rössler,
  • Swapna Verma,
  • Rebekah Street,
  • Andrew Thompson,
  • Alison Ruth Yung,
  • Barnaby Nelson,
  • Patrick D. McGorry,
  • Melanie Föcking,
  • G. Paul Amminger,
  • David Cotter

DOI
https://doi.org/10.1038/s41398-022-02217-0
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 10

Abstract

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Abstract Preliminary 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.