Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes

The Mood Disorders Precision Medicine Consortium (MDPMC)

Research output: Contribution to journalArticle

Abstract

Background: Acylcarnitines have important functions in mitochondrial energetics and β-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profiles can help biochemically distinguish the three phenotypic subtypes of major depressive disorder (MDD): core depression (CD+), anxious depression (ANX+), and neurovegetative symptoms of melancholia (NVSM+). Methods: Depressed outpatients (n = 240) from the Mayo Clinic Pharmacogenomics Research Network were treated with citalopram or escitalopram for eight weeks. Plasma samples collected at baseline and after eight weeks of treatment with citalopram or escitalopram were profiled for short-, medium- and long-chain acylcarnitine levels using AbsoluteIDQ®p180-Kit and LC-MS. Linear mixed effects models were used to examine whether acylcarnitine levels discriminated the clinical phenotypes at baseline or eight weeks post-treatment, and whether temporal changes in acylcarnitine profiles differed between groups. Results: Compared to ANX+, CD+ and NVSM+ had significantly lower concentrations of short- and long-chain acylcarnitines at both baseline and week 8. In NVSM+, the medium- and long-chain acylcarnitines were also significantly lower in NVSM+ compared to ANX+. Short-chain acylcarnitine levels increased significantly from baseline to week 8 in CD+ and ANX+, whereas medium- and long-chain acylcarnitines significantly decreased in CD+ and NVSM+. Conclusions: In depressed patients treated with SSRIs, β-oxidation and mitochondrial energetics as evaluated by levels and changes in acylcarnitines may provide the biochemical basis of the clinical heterogeneity of MDD, especially when combined with clinical characteristics.

Original languageEnglish (US)
Pages (from-to)90-97
Number of pages8
JournalJournal of Affective Disorders
Volume264
DOIs
StatePublished - Mar 1 2020

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Metabolomics
Phenotype
Citalopram
Major Depressive Disorder
acylcarnitine
Depression
Pharmacogenetics
Depressive Disorder
Outpatients
Retrospective Studies

Keywords

  • Acylcarnitines
  • Antidepressants
  • Depression
  • Metabolomics
  • P180
  • Phenotypes

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

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Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes. / The Mood Disorders Precision Medicine Consortium (MDPMC).

In: Journal of Affective Disorders, Vol. 264, 01.03.2020, p. 90-97.

Research output: Contribution to journalArticle

The Mood Disorders Precision Medicine Consortium (MDPMC). / Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes. In: Journal of Affective Disorders. 2020 ; Vol. 264. pp. 90-97.
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abstract = "Background: Acylcarnitines have important functions in mitochondrial energetics and β-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profiles can help biochemically distinguish the three phenotypic subtypes of major depressive disorder (MDD): core depression (CD+), anxious depression (ANX+), and neurovegetative symptoms of melancholia (NVSM+). Methods: Depressed outpatients (n = 240) from the Mayo Clinic Pharmacogenomics Research Network were treated with citalopram or escitalopram for eight weeks. Plasma samples collected at baseline and after eight weeks of treatment with citalopram or escitalopram were profiled for short-, medium- and long-chain acylcarnitine levels using AbsoluteIDQ{\circledR}p180-Kit and LC-MS. Linear mixed effects models were used to examine whether acylcarnitine levels discriminated the clinical phenotypes at baseline or eight weeks post-treatment, and whether temporal changes in acylcarnitine profiles differed between groups. Results: Compared to ANX+, CD+ and NVSM+ had significantly lower concentrations of short- and long-chain acylcarnitines at both baseline and week 8. In NVSM+, the medium- and long-chain acylcarnitines were also significantly lower in NVSM+ compared to ANX+. Short-chain acylcarnitine levels increased significantly from baseline to week 8 in CD+ and ANX+, whereas medium- and long-chain acylcarnitines significantly decreased in CD+ and NVSM+. Conclusions: In depressed patients treated with SSRIs, β-oxidation and mitochondrial energetics as evaluated by levels and changes in acylcarnitines may provide the biochemical basis of the clinical heterogeneity of MDD, especially when combined with clinical characteristics.",
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AU - The Mood Disorders Precision Medicine Consortium (MDPMC)

AU - Ahmed, Ahmed T.

AU - MahmoudianDehkordi, Siamak

AU - Bhattacharyya, Sudeepa

AU - Arnold, Matthias

AU - Liu, Duan

AU - Neavin, Drew

AU - Moseley, M. Arthur

AU - Thompson, J. Will

AU - Williams, Lisa St John

AU - Louie, Gregory

AU - Skime, Michelle K.

AU - Wang, Liewei

AU - Riva-Posse, Patricio

AU - McDonald, William M.

AU - Bobo, William V.

AU - Craighead, W. Edward

AU - Krishnan, Ranga

AU - Weinshilboum, Richard M.

AU - Dunlop, Boadie W.

AU - Millington, David S.

AU - Rush, A. John

AU - Frye, Mark A.

AU - Kaddurah-Daouk, Rima

PY - 2020/3/1

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N2 - Background: Acylcarnitines have important functions in mitochondrial energetics and β-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profiles can help biochemically distinguish the three phenotypic subtypes of major depressive disorder (MDD): core depression (CD+), anxious depression (ANX+), and neurovegetative symptoms of melancholia (NVSM+). Methods: Depressed outpatients (n = 240) from the Mayo Clinic Pharmacogenomics Research Network were treated with citalopram or escitalopram for eight weeks. Plasma samples collected at baseline and after eight weeks of treatment with citalopram or escitalopram were profiled for short-, medium- and long-chain acylcarnitine levels using AbsoluteIDQ®p180-Kit and LC-MS. Linear mixed effects models were used to examine whether acylcarnitine levels discriminated the clinical phenotypes at baseline or eight weeks post-treatment, and whether temporal changes in acylcarnitine profiles differed between groups. Results: Compared to ANX+, CD+ and NVSM+ had significantly lower concentrations of short- and long-chain acylcarnitines at both baseline and week 8. In NVSM+, the medium- and long-chain acylcarnitines were also significantly lower in NVSM+ compared to ANX+. Short-chain acylcarnitine levels increased significantly from baseline to week 8 in CD+ and ANX+, whereas medium- and long-chain acylcarnitines significantly decreased in CD+ and NVSM+. Conclusions: In depressed patients treated with SSRIs, β-oxidation and mitochondrial energetics as evaluated by levels and changes in acylcarnitines may provide the biochemical basis of the clinical heterogeneity of MDD, especially when combined with clinical characteristics.

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