Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes.

Accepted

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ahmed, AT; MahmoudianDehkordi, S; Bhattacharyya, S; Arnold, M; Liu, D; Neavin, D; Moseley, MA; Thompson, JW; Williams, LSJ; Louie, G; Skime, MK; Wang, L; Riva-Posse, P; McDonald, WM; Bobo, WV; Craighead, WE; Krishnan, R; Weinshilboum, RM; Dunlop, BW; Millington, DS; Rush, AJ; Frye, MA; Kaddurah-Daouk, R; Mood Disorders Precision Medicine Consortium (MDPMC),

Published Date

  • March 2020

Published In

Volume / Issue

  • 264 /

Start / End Page

  • 90 - 97

PubMed ID

  • 32056779

Pubmed Central ID

  • 32056779

Electronic International Standard Serial Number (EISSN)

  • 1573-2517

International Standard Serial Number (ISSN)

  • 0165-0327

Digital Object Identifier (DOI)

  • 10.1016/j.jad.2019.11.122

Language

  • eng