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The lipidome in major depressive disorder: Shared genetic influence for ether-phosphatidylcholines, a plasma-based phenotype related to inflammation, and disease risk

Published online by Cambridge University Press:  23 March 2020

E.E.M. Knowles*
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
K. Huynh
Baker Heart and Diabetes Institute, Melbourne, Australia
P.J. Meikle
Baker Heart and Diabetes Institute, Melbourne, Australia
H.H.H. Göring
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
R.L. Olvera
Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
S.R. Mathias
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
R. Duggirala
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
L. Almasy
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
J. Blangero
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
J.E. Curran
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
D.C. Glahn
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA
*Corresponding author. E-mail (E.E.M. Knowles).
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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.

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Copyright © European Psychiatric Association 2017

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