title: Bimodal distribution of polyunsaturated fatty acids in schizophrenia suggests two endophenotypes of the disorder.
abstract: BACKGROUND
  There is conflicting evidence of whether polyunsaturated fatty acids (PUFA) in red blood cells are bimodally distributed in schizophrenia. The purpose of this study was to examine the distribution of PUFA, as well as its links to plausible causal factors.
  
  
  METHODS
  A 16-week cohort study and a case-control study as part of a randomized controlled trial. Ninety-nine patients with DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder, aged 18 to 39, were consecutively included at admission to psychiatric departments of nine Norwegian hospitals. Fatty acids were measured in 97 of these patients and in 20 healthy control subjects. The primary outcome measure was the bimodality test statistic T, assessed by a χ(2) test of the likelihood of one or two normal distributions of PUFA.
  
  
  RESULTS
  At baseline, levels of polyunsaturated fatty acids were highly significantly bimodally distributed among patients. One third of patients constituted a group (low PUFA) who had PUFA levels at one fifth (p < .001) of those in high PUFA patients and healthy control subjects, which did not differ. Bimodality was mainly accounted for by docosahexaenoic acid and arachidonic acid. Bimodality was confirmed after 16 weeks. α-tocopherol was a robust predictor of PUFA at both occasions. Desaturase and elongase indexes differed between PUFA groups. Smoking, gender, antipsychotic medication, and dietary factors did not explain the bimodal distribution.
  
  
  CONCLUSIONS
  Red blood cell PUFA were bimodally distributed among acutely ill patients with schizophrenia and schizoaffective disorder. Endogenous deficiencies of redox regulation or synthesis of long-chain PUFA in the low PUFA group may explain our findings.
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. havard.bentsen@medisin.uio.no
authors.forename: Håvard
authors.initials: H
authors.lastname: Bentsen
authors.forename: Dag K
authors.initials: DK
authors.lastname: Solberg
authors.forename: Helge
authors.initials: H
authors.lastname: Refsum
authors.forename: Jon Michael
authors.initials: JM
authors.lastname: Gran
authors.forename: Thomas
authors.initials: T
authors.lastname: Bøhmer
authors.forename: Peter A
authors.initials: PA
authors.lastname: Torjesen
authors.forename: Ola
authors.initials: O
authors.lastname: Halvorsen
authors.forename: Odd
authors.initials: O
authors.lastname: Lingjærde
mesh_terms: D000123:Acetyltransferases / Q000097:blood; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D058068:Endophenotypes / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000097:blood; D000081031:Fatty Acid Elongases; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000201:enzymology / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000097:blood
chemical_list: D005231:Fatty Acids, Unsaturated; D044943:Fatty Acid Desaturases; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D024502:alpha-Tocopherol