Evidence map›Paper›PMID 27523499›Full record

ArticleThe American journal of psychiatry2017

Neurometabolic Disorders: Potentially Treatable Abnormalities in Patients With Treatment-Refractory Depression and Suicidal Behavior.

Lisa A Pan, Petra Martin, Thomas Zimmer, Anna Maria Segreti, Sivan Kassiff, Brian W McKain, Cynthia A Baca, Manivel Rengasamy, Keith Hyland, Nicolette Walano and 11 more

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

Article in The American journal of psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

36 citing papers in PubMed, 66 citations in OpenAlex.

  1. Trial
  2. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 1 institution in 1 country.

Lisa A PanFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Petra MartinFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Thomas ZimmerFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Anna Maria SegretiFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Sivan KassiffFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Brian W McKainFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Cynthia A BacaFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Manivel RengasamyFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Keith HylandFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Nicolette WalanoFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Robert SteinfeldFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Marion HughesFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Steven K DobrowolskiFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Michele PasquinoFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Rasim DilerFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
James PerelFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
David N FinegoldFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
David G PetersFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Robert K NaviauxFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
David A BrentFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
Jerry VockleyFrom the Departments of Psychiatry, Pediatrics, Human Genetics, Pathology, and Obstetrics and Gynecology, University of Pittsburgh, School of Medicine, Pittsburgh; Medical Neurogenetics Laboratory, Atlanta; the Department of Pediatrics, University Medical Center Göttingen, Göttingen, Germany; and the Departments of Medicine, Pediatrics, and Pathology, School of Medicine, University of California, San Diego.
University of Göttingen · DE

Funding

UNIVERSITY OF PITTSBURGH CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE: BPCAUL1RR024153 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2006 to 2011
$73.9M
University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Functional Magnetic Resonance Imaging Markers of Early-Onset Suicide AttemptK23MH082884 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PAN, LISA · 2009 to 2013
$785k
NCATS NIH HHS UL1 TR000005NCRR NIH HHS UL1 RR024153NIMH NIH HHS K23 MH082884
6 · The paper itself

Abstract

objectiveTreatment-refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. At least 15% of cases of major depressive disorder remain refractory to treatment. The authors previously identified a young adult with treatment-refractory depression and multiple suicide attempts with an associated severe deficiency of CSF tetrahydrobiopterin, a critical cofactor for monoamine neurotransmitter synthesis. Treatment with sapropterin, a tetrahydrobiopterin analogue, led to dramatic and long-lasting remission of depression. This sentinel case led the authors to hypothesize that the incidence of metabolic abnormalities contributing to treatment-refractory depression is underrecognized.

methodThe authors conducted a case-control, targeted, metabolomic evaluation of 33 adolescent and young adult patients with well-characterized histories of treatment-refractory depression (at least three maximum-dose, adequate-duration medication treatments), and 16 healthy comparison subjects. Plasma, urine, and CSF metabolic profiling were performed by coupled gas chromatography/mass spectrometry and high-performance liquid chromatography electrospray ionization tandem mass spectrometry.

resultsCSF metabolite abnormalities were identified in 21 of the 33 participants with treatment-refractory depression. Cerebral folate deficiency (N=12) was most common, with normal serum folate levels and low CSF 5-methyltetrahydrofolate (5-MTHF) levels. All patients with cerebral folate deficiency, including one with low CSF levels of 5-MTHF and tetrahydrobiopterin intermediates, showed improvement in depression symptom inventories after treatment with folinic acid; the patient with low tetrahydrobiopterin also received sapropterin. None of the healthy comparison subjects had a metabolite abnormality.

conclusionsExamination of metabolic disorders in treatment-refractory depression identified an unexpectedly large proportion of patients with potentially treatable abnormalities. The etiology of these abnormalities remains to be determined.

Indexed as

AdolescentDepressive Disorder, Treatment-ResistantDrug Therapy, CombinationFolic AcidFolic Acid DeficiencyHumansSuicide, AttemptedYoung AdultFolic Acid

Identifiers

PMID27523499
PMCPMC10171090
OpenAlexW2510538308

What OpenQuestion holds

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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.