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.


Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
28 10 2022
Historique:
received: 11 03 2022
accepted: 04 10 2022
revised: 21 09 2022
pubmed: 29 10 2022
medline: 2 11 2022
entrez: 28 10 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36307392
doi: 10.1038/s41398-022-02217-0
pii: 10.1038/s41398-022-02217-0
pmc: PMC9616837
doi:

Substances chimiques

Fatty Acids, Omega-3 0
Fatty Acids, Unsaturated 0
Complement System Proteins 9007-36-7

Banques de données

ANZCTR
['12608000475347']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

454

Subventions

Organisme : Health Research Board
ID : HRB ILP POR 2019-005
Pays : Ireland
Organisme : Health Research Board
ID : HRB/HRA/PHR/2015-1293
Pays : Ireland
Organisme : Science Foundation Ireland
ID : 16/RC/3948
Pays : Ireland
Organisme : Wellcome Trust
ID : 220438Z/20/Z
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Subash Raj Susai (SR)

Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland. subashrajsusai@rcsi.ie.

Colm Healy (C)

Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

David Mongan (D)

Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

Meike Heurich (M)

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.

Jonah F Byrne (JF)

Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

Mary Cannon (M)

Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

Gerard Cagney (G)

School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland.

Kieran Wynne (K)

School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland.
Systems Biology Ireland, University College Dublin, Dublin, Ireland.

Connie Markulev (C)

Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Orygen, 35 Poplar Rd, Parkville, VIC, 3052, Australia.

Miriam R Schäfer (MR)

Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Orygen, 35 Poplar Rd, Parkville, VIC, 3052, Australia.

Maximus Berger (M)

Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Department of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.

Nilufar Mossaheb (N)

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.

Monika Schlögelhofer (M)

BioPsyC-Biopsychosocial corporation - Non-Profit association for research funding, Vienna, Austria.

Stefan Smesny (S)

Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.

Ian B Hickie (IB)

Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.

Gregor E Berger (GE)

Child and Adolescent Psychiatric Service of the Canton of Zurich, Zürich, Switzerland.

Eric Y H Chen (EYH)

Department of Psychiatry, University of Hong Kong, Pok Fu Lam, Hong Kong.

Lieuwe de Haan (L)

Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.

Dorien H Nieman (DH)

Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.

Merete Nordentoft (M)

Mental Health Center Copenhagen, Department of clinical Medicine, Copenhagen University Hospital, Copenhagen, Denmark.

Anita Riecher-Rössler (A)

Medical Faculty, University of Basel, Basel, Switzerland.

Swapna Verma (S)

Institute of Mental Health, Singapore, Singapore.

Rebekah Street (R)

Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Orygen, 35 Poplar Rd, Parkville, VIC, 3052, Australia.

Andrew Thompson (A)

Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Orygen, 35 Poplar Rd, Parkville, VIC, 3052, Australia.

Alison Ruth Yung (AR)

Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, VIC, Australia.
School of Health Sciences, University of Manchester, Manchester, UK.

Barnaby Nelson (B)

Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Orygen, 35 Poplar Rd, Parkville, VIC, 3052, Australia.

Patrick D McGorry (PD)

Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Orygen, 35 Poplar Rd, Parkville, VIC, 3052, Australia.

Melanie Föcking (M)

Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.

G Paul Amminger (GP)

Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Orygen, 35 Poplar Rd, Parkville, VIC, 3052, Australia.

David Cotter (D)

Department of Psychiatry, RCSI University of Medicine and Health Sciences, Dublin, Ireland. drcotter@rcsi.ie.

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Classifications MeSH