Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metaboli...

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Published in:Translational psychiatry 2021-03, Vol.11 (1), p.153-14, Article 153
Main Authors: MahmoudianDehkordi, Siamak, Ahmed, Ahmed T., Bhattacharyya, Sudeepa, Han, Xianlin, Baillie, Rebecca A., Arnold, Matthias, Skime, Michelle K., John-Williams, Lisa St, Moseley, M. Arthur, Thompson, J. Will, Louie, Gregory, Riva-Posse, Patricio, Craighead, W. Edward, McDonald, William, Krishnan, Ranga, Rush, A. John, Frye, Mark A., Dunlop, Boadie W., Weinshilboum, Richard M., Kaddurah-Daouk, Rima
Format: Article
Language:English
Subjects:
692/699/476/1414
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Antidepressants
Behavioral Sciences
Biological Psychology
Lipids
Medicine
Medicine & Public Health
Metabolism
Metabolites
Neurosciences
Pharmacotherapy
Psychiatry
Serotonin
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Summary:Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium-chain and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines—including arginine, proline, and methionine sulfoxide—were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism, and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD 17 ). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD 17  ≤ 7) and those who gained no meaningful benefits (
ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-020-01097-6