title: Effects of omega-3 PUFA on immune markers in adolescent individuals at ultra-high risk for psychosis - Results of the randomized controlled Vienna omega-3 study.
abstract: Alterations of immune function have been reported in ultra-high risk (UHR) for psychosis patients causing expectations in terms of predictive meaningfulness and benefits of anti-inflammatory agents. According to a RCT in UHR-patients supplementation of omega-3 polyunsaturated fatty acids (PUFA) was effective in reducing transition to psychosis risk and to improve symptomatology. Based on preclinical findings, we now investigated state marker properties of and the influence of PUFA on immune markers in a RCT (clinical trials.gov Identifier: NCT00396643). In a longitudinal design we measured plasma levels of the pro-inflammatory interleukin 6 (IL-6), the soluble alpha (Tac) subunit of the interleukin 2 receptor (sIL-2r), and the circulating soluble form of the intercellular adhesion molecule one (sICAM-1), in 79 help-seeking UHR individuals (13-25years of age). Using linear mixed model (LMM) analysis, we investigated the effects of 12weeks supplementation of either 1.2g/d PUFA (n=38) or Placebo (n=41). At baseline, inflammatory markers were not altered in patients who later suffered transition to psychosis within one year (n=12; 11 PUFA-group, 1 PL-group). IL-6 was weakly inverse associated with omega-6 PUFA, and highly increased in nicotine users. In univariate tests of the LMM omega-3 PUFA caused a significant increase of sICAM-1 (p=0.022). PUFA did not significantly influence IL-6 or sIL-2r. The enhancement of sICAM-1 in the PUFA condition is suggestive for supportive effects on vascular immune response and immediate Th1 helper cell mediated immune answer, which was found disturbed in manifest schizophrenia, e.g. by facilitating the leukocyte adhesion and migration across the endothelium.
authors.affiliation: Department of Psychiatry, University Hospital Jena, Philosophenweg 3, D-07743 Jena, Germany. Electronic address: stefan.smesny@med.uni-jena.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Smesny
authors.affiliation: Department of Psychiatry, University Hospital Jena, Philosophenweg 3, D-07743 Jena, Germany.
authors.forename: Berko
authors.initials: B
authors.lastname: Milleit
authors.affiliation: The National Centre of Excellence in Youth Mental Health and Orygen Youth Health Research Centre, The University of Melbourne, Locked Bag 10, 35 Poplar Road Parkville, Victoria 3052, Melbourne, Australia; Department of Child and Adolescent Psychiatry, Medical University Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Schaefer
authors.affiliation: Department of Dermatology, University Hospital Jena, Erfurter Straße 35, 07743 Jena, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Hesse
authors.affiliation: Department of Child and Adolescent Psychiatry, Medical University Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Schlögelhofer
authors.affiliation: Department of Psychiatry, University Hospital Jena, Philosophenweg 3, D-07743 Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Langbein
authors.affiliation: Department of Dermatology, University Hospital Jena, Erfurter Straße 35, 07743 Jena, Germany.
authors.forename: Uta-Christina
authors.initials: UC
authors.lastname: Hipler
authors.affiliation: Laboratory of Psychiatric Neuroscience, Australian Institute of Tropical Health and Medicine, (AITHM), 1 James Cook Drive, Townsville, QLD, 4811, Australia; College of Public Health, Medical and Veterinary Science, James Cook University, 1 James Cook, Drive, Townsville, QLD, 4811, Australia.
authors.forename: Maximus
authors.initials: M
authors.lastname: Berger
authors.affiliation: Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland; Department of Psychiatry, Beaumont Hospital, Dublin, Ireland.
authors.forename: David R
authors.initials: DR
authors.lastname: Cotter
authors.affiliation: Department of Psychiatry, University Hospital Jena, Philosophenweg 3, D-07743 Jena, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sauer
authors.affiliation: The National Centre of Excellence in Youth Mental Health and Orygen Youth Health Research Centre, The University of Melbourne, Locked Bag 10, 35 Poplar Road Parkville, Victoria 3052, Melbourne, Australia.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: McGorry
authors.affiliation: The National Centre of Excellence in Youth Mental Health and Orygen Youth Health Research Centre, The University of Melbourne, Locked Bag 10, 35 Poplar Road Parkville, Victoria 3052, Melbourne, Australia; Department of Child and Adolescent Psychiatry, Medical University Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria.
authors.forename: G Paul
authors.initials: GP
authors.lastname: Amminger
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D018450:Disease Progression; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010342:Patient Acceptance of Health Care; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000097:blood / Q000178:diet therapy* / Q000276:immunology* / Q000517:prevention & control; D012306:Risk; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; C508600:IL6 protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1
keywords: At-risk mental state; Biomarker; Cytokines; Endothelium; Immune function; Indicated prevention; Inflammation; Interleukins; Psychosis