Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients.
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Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of action of escitalopram/citalopram focusing on a set of 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 and 8 weeks of drug treatment. The 17-item Hamilton Depression Rating Scale (HRSD17) scores gauged depressive symptom severity. More significant metabolic changes were found after 8 weeks than 4 weeks post baseline. Within the tryptophan pathway, we noted significant reductions in serotonin (5HT) and increases in indoles that are known to be influenced by human gut microbial cometabolism. 5HT, 5-hydroxyindoleacetate (5HIAA), and the ratio of 5HIAA/5HT showed significant correlations to temporal changes in HRSD17 scores. In the tyrosine pathway, changes were observed in the end products of the catecholamines, 3-methoxy-4-hydroxyphenylethyleneglycol and vinylmandelic acid. Furthermore, two phenolic acids, 4-hydroxyphenylacetic acid and 4-hydroxybenzoic acid, produced through noncanconical pathways, were increased with drug exposure. In the purine pathway, significant reductions in hypoxanthine and xanthine levels were observed. Examination of metabolite interactions through differential partial correlation networks revealed changes in guanosine-homogentisic acid and methionine-tyrosine interactions associated with HRSD17. Genetic association studies using the ratios of these interacting pairs of metabolites highlighted two genetic loci harboring genes previously linked to depression, neurotransmission, or neurodegeneration. Overall, exposure to escitalopram/citalopram results in shifts in metabolism through noncanonical pathways, which suggest possible roles for the gut microbiome, oxidative stress, and inflammation-related mechanisms.
Serotonin Uptake Inhibitors
Severity of Illness Index
Depressive Disorder, Major
Published Version (Please cite this version)10.1038/s41398-019-0507-5
Publication InfoArnold, Matthias; Kaddurah-Daouk, Rima; Bhattacharyya, Sudeepa; Ahmed, Ahmed T; Liu, Duan; Luo, Chunqiao; ... Rush, A John (2019). Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients. Translational psychiatry, 9(1). pp. 173. 10.1038/s41398-019-0507-5. Retrieved from https://hdl.handle.net/10161/20597.
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Adjunct Assistant Professor in the Department of Psychiatry and Behavioral Sciences
Professor in Psychiatry and Behavioral Sciences
Overall Research Goals: My research interest over the past decade has focused on scaling up biochemical knowledge for gaining a deeper understanding of the molecular basis of neurodegenerative and neuropsychiatric disorders and finding ways to optimize their treatment. I have also made seminal contributions to the development of the metabolomics field and applications of metabolomics for the study of drug effects, establishing foundations for “Pharmacometabolomi
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