| Autor: |
Siamak MahmoudianDehkordi, Ahmed T. Ahmed, Sudeepa Bhattacharyya, Xianlin Han, Rebecca A. Baillie, Matthias Arnold, Michelle K. Skime, Lisa St. John-Williams, M. Arthur Moseley, J. Will Thompson, Gregory Louie, Patricio Riva-Posse, W. Edward Craighead, William McDonald, Ranga Krishnan, A. John Rush, Mark A. Frye, Boadie W. Dunlop, Richard M. Weinshilboum, Rima Kaddurah-Daouk, The Mood Disorders Precision Medicine Consortium (MDPMC) |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Translational Psychiatry, Vol 11, Iss 1, Pp 1-14 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2158-3188 |
| DOI: |
10.1038/s41398-020-01097-6 |
| Popis: |
Abstract 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 (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17 ≤ 7) and those who gained no meaningful benefits ( |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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