Acylcarnitine Metabolomic Profiles Inform Clinically-Defined Major Depressive Phenotypes

Abstract

BackgroundAcylcarnitines have important functions in mitochondrial energetics and {beta}-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+))--following treatment with a selective serotonin reuptake inhibitor (SSRI).\n\nMethodsDepressed 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 eight weeks post-treatment were profiled for multiple-, short-, medium- and long-chain acylcarnitine levels using AbsoluteIDQ(R)p180-Kit and LC-MS. Linear mixed effects models were used to examine whether acylcarnitine levels discriminate the clinical phenotypes at baseline or eight weeks post-treatment, and whether temporal changes in acylcarnitine profiles differ between groups.\n\nResultsAt baseline, significantly lower concentrations of short- and long-chain acylcarnitines were found in CD+ and NVSM+ compared to ANX+, and the short-chain acylcarnitines remained lower after eight weeks. At eight weeks, the medium- and long-chain acylcarnitines were significantly lower in NVSM+ compared to ANX+. Regarding changes baseline to week eight, short-chain acylcarnitine levels significantly increased in CD+ and ANX+, and medium- and long-chain acylcarnitines significantly decreased in NVSM+ and CD+.\n\nConclusionsIn depressed patients treated with SSRIs, {beta}-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.