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

dc.contributor.author

MahmoudianDehkordi, Siamak

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Ahmed, Ahmed T

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Bhattacharyya, Sudeepa

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Han, Xianlin

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Baillie, Rebecca A

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Arnold, Matthias

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Skime, Michelle K

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John-Williams, Lisa St

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Moseley, M Arthur

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Thompson, J Will

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Louie, Gregory

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Riva-Posse, Patricio

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Craighead, W Edward

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McDonald, William

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Krishnan, Ranga

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Rush, A John

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Frye, Mark A

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Dunlop, Boadie W

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Weinshilboum, Richard M

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Kaddurah-Daouk, Rima

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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

https://hdl.handle.net/10161/25485

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Translational psychiatry

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10.1038/s41398-020-01097-6

dc.subject

Mood Disorders Precision Medicine Consortium (MDPMC)

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Humans

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Amines

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Citalopram

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Lipids

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Carnitine

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Serotonin Uptake Inhibitors

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Antidepressive Agents

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Depression

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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

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School of Medicine

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Basic Science Departments

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Clinical Science Departments

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Pharmacology & Cancer Biology

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Medicine

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Psychiatry & Behavioral Sciences

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Medicine, Cardiology

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Institute for Brain Sciences

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Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

pubs.publication-status

Published

pubs.volume

11

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