@article{1ca1307bd82443b28b6ace5dce3fd6cc,
title = "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",
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.",
author = "Susai, {Subash Raj} and Colm Healy and David Mongan and Meike Heurich and Byrne, {Jonah F.} and Mary Cannon and Gerard Cagney and Kieran Wynne and Connie Markulev and Sch{\"a}fer, {Miriam R.} and Maximus Berger and Nilufar Mossaheb and Monika Schl{\"o}gelhofer and Stefan Smesny and Hickie, {Ian B.} and Berger, {Gregor E.} and Chen, {Eric Y. H.} and {de Haan}, Lieuwe and Nieman, {Dorien H.} and Merete Nordentoft and Anita Riecher-R{\"o}ssler and Swapna Verma and Rebekah Street and Andrew Thompson and Yung, {Alison Ruth} and Barnaby Nelson and McGorry, {Patrick D.} and Melanie F{\"o}cking and Amminger, {G. Paul} and David Cotter",
note = "Funding Information: The NEURAPRO clinical trial (anzctr.org.au Identifier 12608000475347) was supported by the Stanley Medical Research Institute (Grant No. 07TGF-1102 [to PDM, GPA, and BN]), National Health and Medical Research Council (NHMRC) Australia (Grant No. 566529 [to PDM, IBH, ARY, and GPA], NHMRC Senior Research Fellowship Grant No. 1080963 [to GPA], Career Development Fellowship Grant No. 1027532 [to BN], Senior Research Fellowship Grant No. 566593 [to ARY], and Senior Principal Research Fellowship Grant No. 1060996 and Colonial Foundation [to PDM]). This work was supported by an Irish Health Research Board research grant to DC (HRB ILP POR 2019-005), Wellcome Trust Innovation Flagship Award (220438Z/20/Z). This publication has emanated from research supported by Health Research Board (HRB) [to DC, MF] under grant number HRB/HRA/PHR/2015-1293. The research was funded by a research grant from 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: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
day = "1",
doi = "https://doi.org/10.1038/s41398-022-02217-0",
language = "English",
volume = "12",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "1",
}