title: The lipidome in major depressive disorder: Shared genetic influence for ether-phosphatidylcholines, a plasma-based phenotype related to inflammation, and disease risk.
abstract: The lipidome is rapidly garnering interest in the field of psychiatry. Recent studies have implicated lipidomic changes across numerous psychiatric disorders. In particular, there is growing evidence that the concentrations of several classes of lipids are altered in those diagnosed with MDD. However, for lipidomic abnormalities to be considered potential treatment targets for MDD (rather than secondary manifestations of the disease), a shared etiology between lipid concentrations and MDD should be demonstrated.
  
  
  
  In a sample of 567 individuals from 37 extended pedigrees (average size 13.57 people, range=3-80), we used mass spectrometry lipidomic measures to evaluate the genetic overlap between twenty-three biologically distinct lipid classes and a dimensional scale of MDD.
  
  
  
  We found that the lipid class with the largest endophenotype ranking value (ERV, a standardized parametric measure of pleiotropy) were ether-phosphodatidylcholines (alkylphosphatidylcholine, PC(O) and alkenylphosphatidylcholine, PC(P) subclasses). Furthermore, we examined the cluster structure of the twenty-five species within the top-ranked lipid class, and the relationship of those clusters with MDD. This analysis revealed that species containing arachidonic acid generally exhibited the greatest degree of genetic overlap with MDD.
  
  
  
  This study is the first to demonstrate a shared genetic etiology between MDD and ether-phosphatidylcholine species containing arachidonic acid, an omega-6 fatty acid that is a precursor to inflammatory mediators, such as prostaglandins. The study highlights the potential utility of the well-characterized linoleic/arachidonic acid inflammation pathway as a diagnostic marker and/or treatment target for MDD.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. Electronic address: emknowles@gmail.com.
authors.forename: E E M
authors.initials: EEM
authors.lastname: Knowles
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Huynh
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Meikle
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: H H H
authors.initials: HHH
authors.lastname: Göring
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Olvera
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Mathias
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Duggirala
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Almasy
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Blangero
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Glahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D010713:Phosphatidylcholines / Q000235:genetics / Q000378:metabolism*
chemical_list: D010713:Phosphatidylcholines
keywords: Affective disorders; Genetics; Unipolar depression