Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids

Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes...

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Main Authors:	Amminger, G P, Mechelli, A, Rice, S, Kim, S-W, Klier, C M, McNamara, R K, Berk, M, McGorry, P D, Schäfer, M R
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312828/

id	pubmed-4312828
recordtype	oai_dc
spelling	pubmed-43128282015-02-09 Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids Amminger, G P Mechelli, A Rice, S Kim, S-W Klier, C M McNamara, R K Berk, M McGorry, P D Schäfer, M R Original Article Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes. In this study, we sought to determine biological and clinical factors associated with treatment response, here indexed by functional improvement in a pre–post examination of a 12-week randomized controlled intervention in individuals at ultra-high risk (UHR) for psychosis. Participants received either long-chain omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of factors specifically relevant to each intervention, and to be able to contrast them, both treatment groups were investigated in parallel. Univariate linear regression analysis indicated that higher levels of erythrocyte membrane α-linolenic acid (ALA; the parent fatty acid of the ω-3 family) and more severe negative symptoms at baseline predicted subsequent functional improvement in the treatment group, whereas less severe positive symptoms and lower functioning at baseline were predictive in the placebo group. A multivariate machine learning analysis, known as Gaussian Process Classification (GPC), confirmed that baseline fatty acids predicted response to treatment in the ω-3 PUFA group with high levels of sensitivity, specificity and accuracy. In addition, GPC revealed that baseline fatty acids were predictive in the placebo group. In conclusion, our investigation indicates that UHR patients with higher levels of ALA may specifically benefit from ω-3 PUFA supplementation. In addition, multivariate machine learning analysis suggests that fatty acids could potentially be used to inform prognostic evaluations and treatment decisions at the level of the individual. Notably, multiple statistical analyses were conducted in a relatively small sample, limiting the conclusions that can be drawn from what we believe to be a first-of-its-kind study. Additional studies with larger samples are therefore needed to evaluate the generalizability of these findings. Nature Publishing Group 2015-01 2015-01-13 /pmc/articles/PMC4312828/ /pubmed/25585167 http://dx.doi.org/10.1038/tp.2014.134 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Amminger, G P Mechelli, A Rice, S Kim, S-W Klier, C M McNamara, R K Berk, M McGorry, P D Schäfer, M R
spellingShingle	Amminger, G P Mechelli, A Rice, S Kim, S-W Klier, C M McNamara, R K Berk, M McGorry, P D Schäfer, M R Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids
author_facet	Amminger, G P Mechelli, A Rice, S Kim, S-W Klier, C M McNamara, R K Berk, M McGorry, P D Schäfer, M R
author_sort	Amminger, G P
title	Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids
title_short	Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids
title_full	Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids
title_fullStr	Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids
title_full_unstemmed	Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids
title_sort	predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids
description	Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes. In this study, we sought to determine biological and clinical factors associated with treatment response, here indexed by functional improvement in a pre–post examination of a 12-week randomized controlled intervention in individuals at ultra-high risk (UHR) for psychosis. Participants received either long-chain omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of factors specifically relevant to each intervention, and to be able to contrast them, both treatment groups were investigated in parallel. Univariate linear regression analysis indicated that higher levels of erythrocyte membrane α-linolenic acid (ALA; the parent fatty acid of the ω-3 family) and more severe negative symptoms at baseline predicted subsequent functional improvement in the treatment group, whereas less severe positive symptoms and lower functioning at baseline were predictive in the placebo group. A multivariate machine learning analysis, known as Gaussian Process Classification (GPC), confirmed that baseline fatty acids predicted response to treatment in the ω-3 PUFA group with high levels of sensitivity, specificity and accuracy. In addition, GPC revealed that baseline fatty acids were predictive in the placebo group. In conclusion, our investigation indicates that UHR patients with higher levels of ALA may specifically benefit from ω-3 PUFA supplementation. In addition, multivariate machine learning analysis suggests that fatty acids could potentially be used to inform prognostic evaluations and treatment decisions at the level of the individual. Notably, multiple statistical analyses were conducted in a relatively small sample, limiting the conclusions that can be drawn from what we believe to be a first-of-its-kind study. Additional studies with larger samples are therefore needed to evaluate the generalizability of these findings.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312828/
_version_	1613182840598429696

Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids

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