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Acetyl-l-carnitine deficiency in patients with major depressive disorder.

Publication ,  Journal Article
Nasca, C; Bigio, B; Lee, FS; Young, SP; Kautz, MM; Albright, A; Beasley, J; Millington, DS; Mathé, AA; Kocsis, JH; Murrough, JW; McEwen, BS; Rasgon, N
Published in: Proc Natl Acad Sci U S A
August 21, 2018

The lack of biomarkers to identify target populations greatly limits the promise of precision medicine for major depressive disorder (MDD), a primary cause of ill health and disability. The endogenously produced molecule acetyl-l-carnitine (LAC) is critical for hippocampal function and several behavioral domains. In rodents with depressive-like traits, LAC levels are markedly decreased and signal abnormal hippocampal glutamatergic function and dendritic plasticity. LAC supplementation induces rapid and lasting antidepressant-like effects via epigenetic mechanisms of histone acetylation. This mechanistic model led us to evaluate LAC levels in humans. We found that LAC levels, and not those of free carnitine, were decreased in patients with MDD compared with age- and sex-matched healthy controls in two independent study centers. Secondary exploratory analyses showed that the degree of LAC deficiency reflected both the severity and age of onset of MDD. Moreover, these analyses showed that the decrease in LAC was larger in patients with a history of treatment-resistant depression (TRD), among whom childhood trauma and, specifically, a history of emotional neglect and being female, predicted the decreased LAC. These findings suggest that LAC may serve as a candidate biomarker to help diagnose a clinical endophenotype of MDD characterized by decreased LAC, greater severity, and earlier onset as well as a history of childhood trauma in patients with TRD. Together with studies in rodents, these translational findings support further exploration of LAC as a therapeutic target that may help to define individualized treatments in biologically based depression subtype consistent with the spirit of precision medicine.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 21, 2018

Volume

115

Issue

34

Start / End Page

8627 / 8632

Location

United States

Related Subject Headings

  • Sex Factors
  • Middle Aged
  • Male
  • Humans
  • Female
  • Depressive Disorder, Major
  • Carnitine
  • Aged
  • Age Factors
  • Adult
 

Citation

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Nasca, C., Bigio, B., Lee, F. S., Young, S. P., Kautz, M. M., Albright, A., … Rasgon, N. (2018). Acetyl-l-carnitine deficiency in patients with major depressive disorder. Proc Natl Acad Sci U S A, 115(34), 8627–8632. https://doi.org/10.1073/pnas.1801609115
Nasca, Carla, Benedetta Bigio, Francis S. Lee, Sarah P. Young, Marin M. Kautz, Ashly Albright, James Beasley, et al. “Acetyl-l-carnitine deficiency in patients with major depressive disorder.Proc Natl Acad Sci U S A 115, no. 34 (August 21, 2018): 8627–32. https://doi.org/10.1073/pnas.1801609115.
Nasca C, Bigio B, Lee FS, Young SP, Kautz MM, Albright A, et al. Acetyl-l-carnitine deficiency in patients with major depressive disorder. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):8627–32.
Nasca, Carla, et al. “Acetyl-l-carnitine deficiency in patients with major depressive disorder.Proc Natl Acad Sci U S A, vol. 115, no. 34, Aug. 2018, pp. 8627–32. Pubmed, doi:10.1073/pnas.1801609115.
Nasca C, Bigio B, Lee FS, Young SP, Kautz MM, Albright A, Beasley J, Millington DS, Mathé AA, Kocsis JH, Murrough JW, McEwen BS, Rasgon N. Acetyl-l-carnitine deficiency in patients with major depressive disorder. Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):8627–8632.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 21, 2018

Volume

115

Issue

34

Start / End Page

8627 / 8632

Location

United States

Related Subject Headings

  • Sex Factors
  • Middle Aged
  • Male
  • Humans
  • Female
  • Depressive Disorder, Major
  • Carnitine
  • Aged
  • Age Factors
  • Adult