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

Publication ,  Journal Article
MahmoudianDehkordi, S; Ahmed, AT; Bhattacharyya, S; Han, X; Baillie, RA; Arnold, M; Skime, MK; John-Williams, LS; Moseley, MA; Thompson, JW ...
Published in: Transl Psychiatry
March 2, 2021

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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Published In

Transl Psychiatry

DOI

EISSN

2158-3188

Publication Date

March 2, 2021

Volume

11

Issue

1

Start / End Page

153

Location

United States

Related Subject Headings

  • Selective Serotonin Reuptake Inhibitors
  • Lipids
  • Humans
  • Depressive Disorder, Major
  • Depression
  • Citalopram
  • Carnitine
  • Antidepressive Agents
  • Amines
  • 5202 Biological psychology
 

Citation

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MahmoudianDehkordi, S., Ahmed, A. T., Bhattacharyya, S., Han, X., Baillie, R. A., Arnold, M., … Mood Disorders Precision Medicine Consortium (MDPMC), . (2021). Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression. Transl Psychiatry, 11(1), 153. https://doi.org/10.1038/s41398-020-01097-6
MahmoudianDehkordi, Siamak, Ahmed T. Ahmed, Sudeepa Bhattacharyya, Xianlin Han, Rebecca A. Baillie, Matthias Arnold, Michelle K. Skime, et al. “Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression.Transl Psychiatry 11, no. 1 (March 2, 2021): 153. https://doi.org/10.1038/s41398-020-01097-6.
MahmoudianDehkordi S, Ahmed AT, Bhattacharyya S, Han X, Baillie RA, Arnold M, et al. Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression. Transl Psychiatry. 2021 Mar 2;11(1):153.
MahmoudianDehkordi, Siamak, et al. “Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression.Transl Psychiatry, vol. 11, no. 1, Mar. 2021, p. 153. Pubmed, doi:10.1038/s41398-020-01097-6.
MahmoudianDehkordi S, Ahmed AT, Bhattacharyya S, Han X, Baillie RA, Arnold M, Skime MK, John-Williams LS, Moseley MA, Thompson JW, Louie G, Riva-Posse P, Craighead WE, McDonald W, Krishnan R, Rush AJ, Frye MA, Dunlop BW, Weinshilboum RM, Kaddurah-Daouk R, Mood Disorders Precision Medicine Consortium (MDPMC). Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression. Transl Psychiatry. 2021 Mar 2;11(1):153.

Published In

Transl Psychiatry

DOI

EISSN

2158-3188

Publication Date

March 2, 2021

Volume

11

Issue

1

Start / End Page

153

Location

United States

Related Subject Headings

  • Selective Serotonin Reuptake Inhibitors
  • Lipids
  • Humans
  • Depressive Disorder, Major
  • Depression
  • Citalopram
  • Carnitine
  • Antidepressive Agents
  • Amines
  • 5202 Biological psychology