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

E. E M Knowles, K. Huynh, P. J. Meikle, H. H H Göring, Rene L Olvera, S. R. Mathias, R. Duggirala, L. Almasy, J. Blangero, J. E. Curran, D. C. Glahn

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)44-50
Number of pages7
JournalEuropean Psychiatry
Volume43
DOIs
StatePublished - Jun 1 2017

Fingerprint

Major Depressive Disorder
Phosphatidylcholines
Ether
Inflammation
Phenotype
Lipids
Arachidonic Acid
Psychiatry
Omega-6 Fatty Acids
Endophenotypes
Endogenous Retroviruses
Linoleic Acid
Pedigree
Prostaglandins
Mass Spectrometry

Keywords

  • Affective disorders
  • Genetics
  • Unipolar depression

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

The lipidome in major depressive disorder : Shared genetic influence for ether-phosphatidylcholines, a plasma-based phenotype related to inflammation, and disease risk. / Knowles, E. E M; Huynh, K.; Meikle, P. J.; Göring, H. H H; Olvera, Rene L; Mathias, S. R.; Duggirala, R.; Almasy, L.; Blangero, J.; Curran, J. E.; Glahn, D. C.

In: European Psychiatry, Vol. 43, 01.06.2017, p. 44-50.

Research output: Contribution to journalArticle

Knowles, E. E M ; Huynh, K. ; Meikle, P. J. ; Göring, H. H H ; Olvera, Rene L ; Mathias, S. R. ; Duggirala, R. ; Almasy, L. ; Blangero, J. ; Curran, J. E. ; Glahn, D. C. / The lipidome in major depressive disorder : Shared genetic influence for ether-phosphatidylcholines, a plasma-based phenotype related to inflammation, and disease risk. In: European Psychiatry. 2017 ; Vol. 43. pp. 44-50.
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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.",
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T2 - Shared genetic influence for ether-phosphatidylcholines, a plasma-based phenotype related to inflammation, and disease risk

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AU - Huynh, K.

AU - Meikle, P. J.

AU - Göring, H. H H

AU - Olvera, Rene L

AU - Mathias, S. R.

AU - Duggirala, R.

AU - Almasy, L.

AU - Blangero, J.

AU - Curran, J. E.

AU - Glahn, D. C.

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N2 - 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.

AB - 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.

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