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

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 Thisstudy 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.

Alterations in Acylcarnitines, Amines, and Lipids Inform about Mechanism of Action of Citalopram/Escitalopram in Major Depression

“…that contain arachidonic acid, the latter being a precursor to the pro-inflammatory prostaglandins 87 . The initial stages of ether-lipid synthesis occur in the peroxisomes, including the rate-limiting enzymatic processes.…”

Disentangling the genetic overlap between cholesterol and suicide risk

“…The lipid extraction procedure used in this sample has been described in detail elsewhere [16] and is outlined in the Supplemental Materials. Measures of BMI and prescription status for medications linked to metabolic status were collected at this time point.…”

Correction of Fatty Acids Metabolism as Treatment Strategy of Autism

“…In the last decades, researchers have been focused on lipids to make clear idea about it in both physiological and disease sides. Until now, 600 molecular species have been discovered from human plasma described as lipidome [1,2]. Lipidome provides a comprehensive classification of lipids with their structure and function.…”

“…These essential fatty acids found in the diet in the form of α-linolenic acid LA (n-3) and linoleic acid LNA (n-6). These fatty acids contain 18 carbon atoms which can be metabolized to more highly unsaturated members of their family mainly arachidonic [8] and docosahexaenoic acid [1]. The pathway takes place mainly in the liver and may be occur in the other tissues as well.…”