| Autor: |
Siamak MahmoudianDehkordi, Mark A. Frye, A. John Rush, William M. McDonald, Xianlin Han, Gregory Louie, Ahmed T. Ahmed, Rima Kaddurah-Daouk, J. Will Thompson, Richard M. Weinshilboum, M. Arthur Moseley, Boadie W. Dunlop, Lisa St. John-Williams, W. Edward Craighead, Patricio Riva-Posse, Rebecca Baillie, Sudeepa Bhattacharyya, Michelle K. Skime, Matthias Arnold, Ranga R. Krishnan |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| DOI: |
10.1101/2020.02.10.927012 |
| Popis: |
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- 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 (17). Remitters exhibited a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine and serotonin; and b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2 and PC aa C36:4. These findings suggest that mitochondrial energetics – including acylcarnitine metabolism, transport and its link to β-oxidation – and lipid membrane remodeling may play roles in SSRI treatment response. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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