Ahmed T Ahmed1, Siamak MahmoudianDehkordi2, Sudeepa Bhattacharyya3, Matthias Arnold4, Duan Liu5, Drew Neavin6, M Arthur Moseley7, J Will Thompson8, Lisa St John Williams9, Gregory Louie10, Michelle K Skime11, Liewei Wang12, Patricio Riva-Posse13, William M McDonald14, William V Bobo15, W Edward Craighead16, Ranga Krishnan17, Richard M Weinshilboum18, Boadie W Dunlop19, David S Millington20, A John Rush21, Mark A Frye22, Rima Kaddurah-Daouk23. 1. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States. Electronic address: ahmed.ahmed1@mayo.edu. 2. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States; Department of Medicine, Duke University, Durham, NC, United States; Duke Institute of Brain Sciences, Duke University, Durham, NC, United States. Electronic address: siamak.mahmoudiandehkordi@duke.edu. 3. Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United States. Electronic address: SBhattacharyya2@uams.edu. 4. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. Electronic address: matthias.arnold@helmholtz-muenchen.de. 5. Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States. Electronic address: Liu.Duan@mayo.edu. 6. Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States. Electronic address: Neavin.Drew@mayo.edu. 7. Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Durham, NC, United States. Electronic address: arthur.moseley@duke.edu. 8. Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Durham, NC, United States. Electronic address: will.thompson@duke.edu. 9. Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Durham, NC, United States. Electronic address: lisa.stjohn-williams@duke.edu. 10. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States. Electronic address: gregory.louie@duke.edu. 11. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States. Electronic address: skime.Michelle@mayo.edu. 12. Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States. Electronic address: Wang.Liewei@mayo.edu. 13. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: privapo@emory.edu. 14. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: wmcdona@emory.edu. 15. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States. Electronic address: Bobo.William@mayo.edu. 16. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: ecraigh@emory.edu. 17. Department of Psychiatry, Rush Medical College, Chicago, IL, United States. Electronic address: Ranga_Krishnan@rush.edu. 18. Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States. Electronic address: Weinshilboum.Richard@mayo.edu. 19. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: bdunlop@emory.edu. 20. Professor Emeritus, Department of Pediatrics, Duke University School of Medicine, Durham, NC, United States. Electronic address: milli014@duke.edu. 21. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States; Department of Psychiatry, Health Sciences Center, Texas Tech University, Permian Basin, TX, United States; Duke-National University of Singapore, Singapore. 22. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States. Electronic address: mfrye@mayo.edu. 23. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States; Department of Medicine, Duke University, Durham, NC, United States; Duke Institute of Brain Sciences, Duke University, Durham, NC, United States. Electronic address: rima.kaddurahdaouk@duke.edu.
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.
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 depressedpatients 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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