Evidence map›Paper›PMID 26364548›Full record

ArticleBiological psychiatry2016

Markedly Lower Glutamic Acid Decarboxylase 67 Protein Levels in a Subset of Boutons in Schizophrenia.

Brad R Rocco, David A Lewis, Kenneth N Fish

Open access · greenAbstract read
In one paragraph

Article in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 4 pooled it
2.7field-weighted citation impact, top 10% 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

42 citing papers in PubMed, 4 syntheses or guidelines pooled it, 59 citations in OpenAlex.

  1. Pooled it
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  4. Cortical control of chandelier cells in neural codes.Frontiers in cellular neuroscience · 2022
    Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Brad R RoccoDepartments of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
David A LewisDepartments of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Kenneth N FishDepartments of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: fishkn@upmc.edu.
University of Pittsburgh · US

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
SCHIZOPHRENIA AND CORTICAL DOPAMINE/GABA INTERACTIONSR01MH043784 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 1988 to 2023
$7.2M
GABA Neurons and Cortical Circuitry in SchizophreniaR37MH043784 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 2001 to 2010
$6.8M
Chandelier cell inputs to pyramidal neurons in schizophrenia and developmentR01MH096985 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FISH, KENNETH N · 2012 to 2015
$1.2M
NCATS NIH HHS UL1 TR000005NIMH NIH HHS R01 MH043784NIMH NIH HHS R01 MH096985NIMH NIH HHS R37 MH043784
6 · The paper itself

Abstract

backgroundConvergent findings indicate that cortical gamma-aminobutyric acid (GABA)ergic circuitry is altered in schizophrenia. Postmortem studies have consistently found lower levels of glutamic acid decarboxylase 67 (GAD67) messenger RNA (mRNA) in the prefrontal cortex (PFC) of subjects with schizophrenia. At the cellular level, the density of GABA neurons with detectable levels of GAD67 mRNA is ~30% lower across cortical layers. Knowing how this transcript deficit translates to GAD67 protein levels in axonal boutons is important for understanding the impact it might have on GABA synthesis. In addition, because reductions in GAD67 expression before, but not after, the maturation of GABAergic boutons results in a lower density of GABAergic boutons in mouse cortical cultures, knowing if GABAergic bouton density is altered in schizophrenia would provide insight into the timing of the GAD67 deficit.

methodsPFC tissue sections from 20 matched pairs of schizophrenia and comparison subjects were immunolabeled for the vesicular GABA transporter (vGAT) and GAD67.

resultsvGAT+ bouton density did not differ between subject groups, consistent with findings that vGAT mRNA levels are unaltered in the illness and confirming that the number of cortical GABAergic boutons is not lower in schizophrenia. In contrast, in schizophrenia subjects, the proportion of vGAT+ boutons with detectable GAD67 levels (vGAT+/GAD67+ boutons) was 16% lower and mean GAD67 levels were 14% lower in the remaining vGAT+/GAD67+ boutons.

conclusionsOur findings suggest that GABA production is markedly reduced in a subset of boutons in the PFC of schizophrenia subjects and that this reduction likely occurs after the maturation of GABAergic boutons.

Indexed as

AdultAutopsyFemaleGABAergic Neuronsgamma-Aminobutyric AcidGlutamate DecarboxylaseHumansMaleMiddle AgedPrefrontal CortexPresynaptic TerminalsSchizophreniaVesicular Inhibitory Amino Acid Transport Proteinsgamma-Aminobutyric AcidGlutamate Decarboxylaseglutamate decarboxylase 1SLC32A1 protein, humanVesicular Inhibitory Amino Acid Transport ProteinsDevelopmentGABAergicGAD67Gamma-aminobutyric acidQuantitative microscopyvGAT

Identifiers

PMID26364548
PMCPMC4744808
OpenAlexW1659737704

What OpenQuestion holds

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LicenceTDM
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.