The Lipidome in Major Depressive Disorder: Shared Genetic Influence for Ether-Phosphatidylcholines, a Plasma-Based Phenotype Related to Inflammation, and Disease Risk

Authors

Emma E. M. Knowles
Kevin Huynh
Peter J. Meikle, Baker Heart and Diabetes Institute
Harald H. H. Goring, The University of Texas Rio Grande Valley
Rene L. Olvera
Samuel R. Mathias
Ravi Duggirala, The University of Texas Rio Grande Valley
Laura Almasy, The University of Texas Rio Grande Valley
John Blangero, The University of Texas Rio Grande Valley
Joanne E. Curran, The University of Texas Rio Grande Valley
David C. Glahn, Olin Neuropsychiatry Research Center

Document Type

Article

Publication Date

6-2017

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Recommended Citation

Knowles, E. E. M., Huynh, K., Meikle, P. J., Göring, H. H. H., Olvera, R. L., Mathias, S. R., Duggirala, R., Almasy, L., Blangero, J., Curran, J. E., & Glahn, D. C. (2017). The lipidome in major depressive disorder: Shared genetic influence for ether-phosphatidylcholines, a plasma-based phenotype related to inflammation, and disease risk. European psychiatry : the journal of the Association of European Psychiatrists, 43, 44–50. https://doi.org/10.1016/j.eurpsy.2017.02.479

Publication Title

Eur Psychiatry

DOI

10.1016/j.eurpsy.2017.02.479

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics