TY - JOUR
T1 - Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes
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
N1 - Publisher Copyright:
© 2019
PY - 2020/3/1
Y1 - 2020/3/1
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.
AB - 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.
KW - Acylcarnitines
KW - Antidepressants
KW - Depression
KW - Metabolomics
KW - P180
KW - Phenotypes
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U2 - 10.1016/j.jad.2019.11.122
DO - 10.1016/j.jad.2019.11.122
M3 - Article
C2 - 32056779
AN - SCOPUS:85076602119
SN - 0165-0327
VL - 264
SP - 90
EP - 97
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -