TY - JOUR
T1 - The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning
T2 - An analysis of the NEURAPRO clinical trial
AU - Susai, Subash Raj
AU - Mongan, David
AU - Healy, Colm
AU - Cannon, Mary
AU - Nelson, Barnaby
AU - Markulev, Connie
AU - Schäfer, Miriam R.
AU - Berger, Maximus
AU - Mossaheb, Nilufar
AU - Schlögelhofer, Monika
AU - Smesny, Stefan
AU - Hickie, Ian B.
AU - Berger, Gregor E.
AU - Chen, Eric Y. H.
AU - de Haan, Lieuwe
AU - Nieman, Dorien H.
AU - Nordentoft, Merete
AU - Riecher-Rössler, Anita
AU - Verma, Swapna
AU - Thompson, Andrew
AU - Yung, Alison Ruth
AU - McGorry, Patrick D.
AU - Föcking, Melanie
AU - Cotter, David
AU - Amminger, G. Paul
N1 - Funding Information: We would like to thank the participants and their families. We express our thanks to Mr. John Butler from Mesoscale diagnostics for his guidance and support to run the multiplex assays. We express our sincere thanks to Hok Pan Yuen from ORYGEN for his contribution in clinical data acquisition for the NEURAPRO study. This publication has emanated from research supported by Health Research Board (HRB) [to DC, MF, MC] under grant number HRB/HRA/PHR/2015-1293. The research was funded in part 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. The immune marker study was supported by Orygen, Australia. DM is a Fellow on the Irish Clinical Academic Training (ICAT) Programme which is supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland. MC and CH were supported by a European Research Council Consolidator grand awarded to M Cannon (iHEAR, Grant Code: 724809). 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 Australia (Grant No. 566529 [to PDM, IBH, ARY, and GPA], Grant No. 509388 [to GPA and PDM], Senior Research Fellowship Grant No. 1080963 [to GPA], Senior Research Fellowship Grant No. 566593 and Principal Research Fellowship Grant No. GNT1136829 [to ARY], Career Development Fellowship Grant No. 1027532 and Senior Research Fellowship No. 1137687 [to BN], and Senior Principal Research Fellowship Grant No. 1060996 [to PDM]), Colonial Foundation (to PDM), and National Alliance for Research on Schizophrenia and Depression (to PDM). PDM reports receiving unrestricted research funding from AstraZeneca, Eli Lilly and Company, Janssen-Cilag, Pfizer, and Novartis and honoraria for educational activities with AstraZeneca, Eli Lilly and Company, Janssen-Cilag, Pfizer, Bristol-Myers Squibb, Roche Holding AG, and the Lundbeck Institute. Funding Information: This publication has emanated from research supported by Health Research Board (HRB) [to DC, MF, MC] under grant number HRB/HRA/PHR/2015-1293. The research was funded in part 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. The immune marker study was supported by Orygen, Australia. DM is a Fellow on the Irish Clinical Academic Training (ICAT) Programme which is supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland. MC and CH were supported by a European Research Council Consolidator grand awarded to M Cannon (iHEAR, Grant Code: 724809). Publisher Copyright: © 2021
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
AB - 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.
KW - Biological marker
KW - Immune markers and clinically high-risk
KW - Omega 3 fatty acid
KW - n-3 poly unsaturated fatty acid
UR - http://www.scopus.com/inward/record.url?scp=85116673880&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bbi.2021.09.018
DO - https://doi.org/10.1016/j.bbi.2021.09.018
M3 - Article
C2 - 34624483
SN - 0889-1591
VL - 99
SP - 147
EP - 156
JO - Brain, behavior, and immunity
JF - Brain, behavior, and immunity
ER -