title: Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia.
abstract: BACKGROUND
  Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission.
  
  
  METHODS
  Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples.
  
  
  RESULTS
  In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed.
  
  
  CONCLUSIONS
  Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins.
authors.affiliation: VTT Technical Research Centre of Finland, Tietotie 2, Espoo, FI-02044 VTT, Finland. matej.oresic@vtt.fi.
authors.forename: Matej
authors.initials: M
authors.lastname: Orešič
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Seppänen-Laakso
authors.forename: Daqiang
authors.initials: D
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.forename: Sebastian
authors.initials: S
authors.lastname: Therman
authors.forename: Rachael
authors.initials: R
authors.lastname: Viehman
authors.forename: Ulla
authors.initials: U
authors.lastname: Mustonen
authors.forename: Theo G
authors.initials: TG
authors.lastname: van Erp
authors.forename: Tuulia
authors.initials: T
authors.lastname: Hyötyläinen
authors.forename: Paul
authors.initials: P
authors.lastname: Thompson
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Matti O
authors.initials: MO
authors.lastname: Huttunen
authors.forename: Jaana
authors.initials: J
authors.lastname: Suvisaari
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Jouko
authors.initials: J
authors.lastname: Lönnqvist
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon