Evidence map›Paper›PMID 30061399›Full record

Trial reportProceedings of the National Academy of Sciences of the United States of America2018

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

Carla Nasca, Benedetta Bigio, Francis S Lee, Sarah P Young, Marin M Kautz, Ashly Albright, James Beasley, David S Millington, Aleksander A Mathé, James H Kocsis and 3 more

Open access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 3 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 3 syntheses or guidelines pooled it, 146 citations in OpenAlex.

  1. Pooled it
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  4. Trial
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  6. Review
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  8. Review
  9. [Gender differences in acylcarnitine metabolism among patients with depression disorder].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Article
  10. Article
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  12. Review
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  17. Plasma and ovarian metabolomic responses to chronic stress in female mice.Metabolomics : Official journal of the Metabolomic Society · 2025
    Article
  18. Review
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  20. Article

25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 2 countries.

Carla NascaHarold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065; cnasca@rockefeller.edu mcewen@rockefeller.edu.
Benedetta BigioHarold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065.
Francis S LeeSackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY 10065.
Sarah P YoungDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710.
Marin M KautzMood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Ashly AlbrightDepartment of Psychiatry, Weill Cornell Medical College, New York, NY 10065.
James BeasleyBiochemical Genetics Laboratory, Duke University Health System, Durham, NC 27710.
David S MillingtonDivision of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710.
Aleksander A MathéDepartment of Clinical Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
James H KocsisDepartment of Psychiatry, Weill Cornell Medical College, New York, NY 10065.
James W MurroughMood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Bruce S McEwenHarold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065; cnasca@rockefeller.edu mcewen@rockefeller.edu.
Natalie RasgonHarold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065.
Cornell University · USRockefeller University · USDuke University Health System · USIcahn School of Medicine at Mount Sinai · USDuke University · USKarolinska Institutet · SEStanford University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

AcetylcarnitineAdultAgedAge FactorsCarnitineFemaleHumansMajor Depressive DisorderMaleMiddle AgedSex FactorsAcetylcarnitineCarnitinechildhood traumaepigeneticglutamatemGlu2treatment-resistant depression

Identifiers

PMID30061399
PMCPMC6112703
OpenAlexW2886666079

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.