title: Implications of lipid biology for the pathogenesis of schizophrenia.
abstract: OBJECTIVE
  Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia.
  
  
  METHODS
  Medline databases were searched from 1966 to 2001 followed by the cross-checking of references.
  
  
  RESULTS
  Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used.
  
  
  CONCLUSIONS
  Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.
authors.affiliation: Early Psychosis Prevention and Intervention Centre, MH-SKY (EPPIC), Victoria. gregor@unimelb.edu.au
authors.forename: Gregor E
authors.initials: GE
authors.lastname: Berger
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wood
authors.forename: Christos
authors.initials: C
authors.lastname: Pantelis
authors.forename: Dennis
authors.initials: D
authors.lastname: Velakoulis
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wellard
authors.forename: Patrick D
authors.initials: PD
authors.lastname: McGorry
mesh_terms: D005228:Fatty Acids, Essential / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D005228:Fatty Acids, Essential