Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression.
dc.contributor.author | MahmoudianDehkordi, Siamak | |
dc.contributor.author | Ahmed, Ahmed T | |
dc.contributor.author | Bhattacharyya, Sudeepa | |
dc.contributor.author | Han, Xianlin | |
dc.contributor.author | Baillie, Rebecca A | |
dc.contributor.author | Arnold, Matthias | |
dc.contributor.author | Skime, Michelle K | |
dc.contributor.author | John-Williams, Lisa St | |
dc.contributor.author | Moseley, M Arthur | |
dc.contributor.author | Thompson, J Will | |
dc.contributor.author | Louie, Gregory | |
dc.contributor.author | Riva-Posse, Patricio | |
dc.contributor.author | Craighead, W Edward | |
dc.contributor.author | McDonald, William | |
dc.contributor.author | Krishnan, Ranga | |
dc.contributor.author | Rush, A John | |
dc.contributor.author | Frye, Mark A | |
dc.contributor.author | Dunlop, Boadie W | |
dc.contributor.author | Weinshilboum, Richard M | |
dc.contributor.author | Kaddurah-Daouk, Rima | |
dc.contributor.author | Mood Disorders Precision Medicine Consortium (MDPMC) | |
dc.date.accessioned | 2022-07-11T20:34:46Z | |
dc.date.available | 2022-07-11T20:34:46Z | |
dc.date.issued | 2021-03-02 | |
dc.date.updated | 2022-07-11T20:34:45Z | |
dc.description.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 (<30% reduction in HRSD17). 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. | |
dc.identifier | 10.1038/s41398-020-01097-6 | |
dc.identifier.issn | 2158-3188 | |
dc.identifier.issn | 2158-3188 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.relation.ispartof | Translational psychiatry | |
dc.relation.isversionof | 10.1038/s41398-020-01097-6 | |
dc.subject | Mood Disorders Precision Medicine Consortium (MDPMC) | |
dc.subject | Humans | |
dc.subject | Amines | |
dc.subject | Citalopram | |
dc.subject | Lipids | |
dc.subject | Carnitine | |
dc.subject | Serotonin Uptake Inhibitors | |
dc.subject | Antidepressive Agents | |
dc.subject | Depression | |
dc.subject | Depressive Disorder, Major | |
dc.title | Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression. | |
dc.type | Journal article | |
duke.contributor.orcid | Arnold, Matthias|0000-0002-4666-0923 | |
duke.contributor.orcid | Rush, A John|0000-0003-2004-2382 | |
pubs.begin-page | 153 | |
pubs.issue | 1 | |
pubs.organisational-group | Duke | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Pharmacology & Cancer Biology | |
pubs.organisational-group | Medicine | |
pubs.organisational-group | Psychiatry & Behavioral Sciences | |
pubs.organisational-group | Medicine, Cardiology | |
pubs.organisational-group | Institutes and Provost's Academic Units | |
pubs.organisational-group | University Institutes and Centers | |
pubs.organisational-group | Duke Institute for Brain Sciences | |
pubs.organisational-group | Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences | |
pubs.publication-status | Published | |
pubs.volume | 11 |
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