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- W3004872010 abstract "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- 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 (<30% reduction in HRSD 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." @default.
- W3004872010 created "2020-02-14" @default.
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- W3004872010 date "2020-02-10" @default.
- W3004872010 modified "2023-10-16" @default.
- W3004872010 title "Alterations in Acylcarnitines, Amines, and Lipids Inform about Mechanism of Action of Citalopram/Escitalopram in Major Depression" @default.
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