Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial

Nicholas Cheng; Alison Mclaverty; 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-Rössler; Swapna Verma; Rebekah Street; Andrew Thompson; Hok Pan Yuen; Robert Hester; Alison Ruth Yung; Patrick D. Mcgorry; Kelly Allott; G. Paul Amminger

doi:10.1192/bjo.2022.572

Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial

Nicholas Cheng^*
, Alison Mclaverty
, 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-Rössler
, Swapna Verma
, Rebekah Street
, Andrew Thompson
, Hok Pan Yuen

Robert Hester, Alison Ruth Yung, Patrick D. Mcgorry, Kelly Allott, G. Paul Amminger

^*Corresponding author for this work

University of Melbourne
University of Bern
Medical University of Vienna
BioPsyC-Biopsychosocial Corporation – Non-Profit Association for Research Funding
Friedrich Schiller University Jena
The University of Sydney
Child and Adolescent Psychiatric Service of the Canton of Zurich
The University of Hong Kong
University of Copenhagen
Medizinischen Fakultät
Singapore Institute of Mental Health
Deakin University
Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. Aims To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis. Method Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n-3 PUFA levels predicted change in cognitive performance. Results The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months. Conclusions We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n-3 PUFAs.

Original language	English
Article number	e165
Journal	BJPsych open
Volume	8
Issue number	5
DOIs	https://doi.org/10.1192/bjo.2022.572
Publication status	Published - 8 Sept 2022

Keywords

Cognition
clinical high risk
early intervention
psychotic disorders
randomised controlled trial

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Cheng, N., Mclaverty, A., Nelson, B., Markulev, C., Schäfer, M. R., Berger, M., Mossaheb, N., Schlögelhofer, M., Smesny, S., Hickie, I. B., Berger, G. E., Chen, E. Y. H., de Haan, L., Nieman, D. H., Nordentoft, M., Riecher-Rössler, A., Verma, S., Street, R., Thompson, A., ... Amminger, G. P. (2022). Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial. BJPsych open, 8(5), Article e165. https://doi.org/10.1192/bjo.2022.572

@article{1be33af163cd4a21b239226568ca0add,

title = "Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial",

abstract = "Background Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. Aims To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis. Method Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n-3 PUFA levels predicted change in cognitive performance. Results The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months. Conclusions We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n-3 PUFAs.",

keywords = "Cognition, clinical high risk, early intervention, psychotic disorders, randomised controlled trial",

author = "Nicholas Cheng and Alison Mclaverty and Barnaby Nelson 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 Yuen, \{Hok Pan\} and Robert Hester and Yung, \{Alison Ruth\} and Mcgorry, \{Patrick D.\} and Kelly Allott and Amminger, \{G. Paul\}",

note = "Funding Information: This work was supported by grant 07TGF-1102 from the Stanley Medical Research Institute, grant 566529 from the National Health and Medical Research Council of Australia (NHMRC) Australia Program (to P.D.M., I.B.H., A.R.Y. and G.P.A.) and a grant from the Colonial Foundation. K.A. was supported by a Career Development Fellowship from the NHMRC (1141207) and a Dame Kate Campbell Fellowship from The University of Melbourne; G.P.A. and A.R.Y. were supported by NHMRC Senior Research Fellowships 1080963 and 566593 respectively; B.N. was supported by NHMRC Career Development Fellowship 1027532; and P.D.M. was supported by NHMRC Senior Principal Research Fellowship 1060996. Publisher Copyright: Copyright {\textcopyright} 2022 The Author(s). Published by Cambridge University Press on behalf of the Royal College of Psychiatrists.",

year = "2022",

month = sep,

day = "8",

doi = "10.1192/bjo.2022.572",

language = "English",

volume = "8",

journal = "BJPsych open",

issn = "2056-4724",

publisher = "Cambridge University Press",

number = "5",

}

Cheng, N, Mclaverty, A, Nelson, B, Markulev, C, Schäfer, MR, Berger, M, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Street, R, Thompson, A, Yuen, HP, Hester, R, Yung, AR, Mcgorry, PD, Allott, K & Amminger, GP 2022, 'Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial', BJPsych open, vol. 8, no. 5, e165. https://doi.org/10.1192/bjo.2022.572

Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial. / Cheng, Nicholas; Mclaverty, Alison; Nelson, Barnaby et al.
In: BJPsych open, Vol. 8, No. 5, e165, 08.09.2022.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis

T2 - secondary analysis of the NEURAPRO randomised controlled trial

AU - Cheng, Nicholas

AU - Mclaverty, Alison

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 - Street, Rebekah

AU - Thompson, Andrew

AU - Yuen, Hok Pan

AU - Hester, Robert

AU - Yung, Alison Ruth

AU - Mcgorry, Patrick D.

AU - Allott, Kelly

AU - Amminger, G. Paul

N1 - Funding Information: This work was supported by grant 07TGF-1102 from the Stanley Medical Research Institute, grant 566529 from the National Health and Medical Research Council of Australia (NHMRC) Australia Program (to P.D.M., I.B.H., A.R.Y. and G.P.A.) and a grant from the Colonial Foundation. K.A. was supported by a Career Development Fellowship from the NHMRC (1141207) and a Dame Kate Campbell Fellowship from The University of Melbourne; G.P.A. and A.R.Y. were supported by NHMRC Senior Research Fellowships 1080963 and 566593 respectively; B.N. was supported by NHMRC Career Development Fellowship 1027532; and P.D.M. was supported by NHMRC Senior Principal Research Fellowship 1060996. Publisher Copyright: Copyright © 2022 The Author(s). Published by Cambridge University Press on behalf of the Royal College of Psychiatrists.

PY - 2022/9/8

Y1 - 2022/9/8

N2 - Background Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. Aims To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis. Method Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n-3 PUFA levels predicted change in cognitive performance. Results The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months. Conclusions We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n-3 PUFAs.

AB - Background Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. Aims To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis. Method Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n-3 PUFA levels predicted change in cognitive performance. Results The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months. Conclusions We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n-3 PUFAs.

KW - Cognition

KW - clinical high risk

KW - early intervention

KW - psychotic disorders

KW - randomised controlled trial

UR - https://www.scopus.com/pages/publications/85140268181

U2 - 10.1192/bjo.2022.572

DO - 10.1192/bjo.2022.572

M3 - Article

C2 - 36073014

SN - 2056-4724

VL - 8

JO - BJPsych open

JF - BJPsych open

IS - 5

M1 - e165

ER -

Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial

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