title: Predictors of treatment response in young people at ultra-high risk for psychosis who received long-chain omega-3 fatty acids.
abstract: 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.
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne Centre for Youth Mental Health and Melbourne Health, Parkville, VIC, Australia.
authors.forename: G P
authors.initials: GP
authors.lastname: Amminger
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Mechelli
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne Centre for Youth Mental Health and Melbourne Health, Parkville, VIC, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Rice
authors.affiliation: Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: S-W
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: C M
authors.initials: CM
authors.lastname: Klier
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: McNamara
authors.affiliation: School of Medicine, Deakin University, Geelong, VIC, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Berk
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne Centre for Youth Mental Health and Melbourne Health, Parkville, VIC, Australia.
authors.forename: P D
authors.initials: PD
authors.lastname: McGorry
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne Centre for Youth Mental Health and Melbourne Health, Parkville, VIC, Australia.
authors.forename: M R
authors.initials: MR
authors.lastname: Schäfer
mesh_terms: D000293:Adolescent; D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000627:therapeutic use*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000627:therapeutic use*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D006801:Humans; D016014:Linear Models; D019787:Linoleic Acid / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D011618:Psychotic Disorders / Q000188:drug therapy*; D012306:Risk; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*; D055815:Young Adult; D017962:alpha-Linolenic Acid / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D014815:Vitamins; D017962:alpha-Linolenic Acid; D014810:Vitamin E; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid; C026219:docosapentaenoic acid