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The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: an analysis of the NEURAPRO clinical trial

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posted on 2021-10-28, 15:39 authored by Subash Raj SusaiSubash Raj Susai, David Mongan, Colm HealyColm Healy, Mary CannonMary Cannon, Barnaby Nelson, 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-Rossler, Swapna Verma, Andrew Thompson, Alison Ruth Yung, Patrick D. McGorry, Melanie FockingMelanie Focking, David CotterDavid Cotter, Paul Amminger
Background: There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample. In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 FAs and clinical outcomes were mediated via plasma immune markers. Clinical outcomes for CHR participants in the NEURAPRO clinical trial were measured using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) scales. The erythrocyte omega-3 index [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] and plasma concentrations of inflammatory markers were quantified at baseline (n = 268) and 6 month follow-up (n = 146) by gas chromatography and multiplex immunoassay, respectively. In linear regression models, the baseline plasma concentrations of Interleukin (IL)-15, Intercellular adhesion molecule (ICAM)-1 and Vascular cell adhesion molecule (VCAM)-1 were negatively associated with baseline omega-3 index. In addition, 6-month change in IL-12p40 and TNF-α showed a negative association with change in omega-3 index. In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with VCAM-1 and TNF-α respectively at follow-up. Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 FAs and clinical outcomes (psychotic symptoms and functioning) in CHR participants. Our results indicate a predominantly anti-inflammatory relationship of omega-3 FAs on plasma inflammatory status in CHR individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up. Both immune and non-immune biological effects of omega-3 FAs would be resourceful in understanding the clinical benefits of omega-3 FAs in CHR papulation.


Health Research Board (HRB) under grant number HRB/HRA/PHR/2015-1293

Science Foundation Ireland (SFI) under Grant Number 412 16/RC/3948

European Regional Development Fund

FutureNeuro industry partners

Orygen, Australia

Irish Clinical Academic Training (ICAT) Programme

Wellcome Trust

Health Research Board (Grant Number 203930/B/16/Z)

Health Service Executive National Doctors Training and Planning

Health and Social Care, Research and Development Division, Northern Ireland

European Research Council Consolidator grant (iHEAR, Grant Code: 724809)

Stanley Medical Research Institute (Grant No. 07TGF-1102)

National Health and Medical Research Council Australia (Grant No. 56652; Grant No. 509388; Senior Research Fellowship Grant No. 1080963; Senior Research Fellowship Grant No. 566593; Principal Research Fellowship Grant No. GNT1136829; Career Development Fellowship Grant No 1027532; Senior Research Fellowship No. 1137687; Senior Principal Research Fellowship Grant No. 1060996)

Colonial Foundation

National Alliance for Research on Schizophrenia and Depression



The original article is available from

Published Citation

Susai SR, et al. The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial. Brain Behav Immun. 2021 5;99:147-156.

Publication Date

5 October 2021

PubMed ID



  • Psychiatry

Research Area

  • Immunity, Infection and Inflammation
  • Neurological and Psychiatric Disorders
  • Population Health and Health Services


Elsevier BV


  • Accepted Version (Postprint)