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MahmoudianDehkordi, S.* ; Ahmed, A.T.* ; Bhattacharyya, S.* ; Han, X.* ; Baillie, R.A.* ; Arnold, M. ; Skime, M.K.* ; John-Williams, L.S.* ; Moseley, M.A.* ; Thompson, J.W.* ; Louie, G.* ; Riva-Posse, P.* ; Craighead, W.E.* ; McDonald, W.* ; Krishnan, R.* ; Rush, A.J.* ; Frye, M.A.* ; Dunlop, B.W.* ; Weinshilboum, R.M.* ; Kaddurah-Daouk, R.*

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

Transl. Psychiatry 11:153 (2021)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Fatty-acid Oxidation; Acetyl-l-carnitine; Mitochondrial-function; Disorders; Methionine; Outcomes; Metabolomics; Cholesterol; Remission; Diagnosis

ISSN (print) / ISBN 2158-3188

e-ISSN 2158-3188

Journal Translational Psychiatry

Quellenangaben Volume: 11, Issue: 1, Article Number: 153

Publisher Nature Publishing Group

Publishing Place Campus, 4 Crinan St, London, N1 9xw, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)

Grants U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)