Evidence map›Paper›PMID 38176569›Full record

ArticleNeurobiology of disease2024

Scaling of smaller pyramidal neuron size and lower energy production in schizophrenia.

Kirsten E Schoonover, Nora E Miller, Kenneth N Fish, David A Lewis

Open access · goldAbstract read
In one paragraph

Article in Neurobiology of disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Altered excitatory and inhibitory ionotropic receptor subunit expression in the cortical visuospatial working memory network in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
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

4 authors at 1 institution in 1 country.

Kirsten E SchoonoverTranslational Neuroscience Program, Department of Psychiatry, School of Medicine, University of Pittsburgh, Department of Psychiatry Biomedical Science Tower, W1653 3811 O'Hara Street Pittsburgh, PA 15213, United States of America.
Nora E MillerDepartment of Neuroscience, Dietrich School of Arts and Sciences, University of Pittsburgh, Department of Psychiatry, Biomedical Science Tower W1653 3811 O'Hara Street Pittsburgh, PA 15213, United States of America.
Kenneth N FishTranslational Neuroscience Program, Department of Psychiatry, School of Medicine, University of Pittsburgh, Department of Psychiatry Biomedical Science Tower, W1653 3811 O'Hara Street Pittsburgh, PA 15213, United States of America.
David A LewisTranslational Neuroscience Program, Department of Psychiatry, School of Medicine, University of Pittsburgh, Department of Psychiatry Biomedical Science Tower, W1653 3811 O'Hara Street Pittsburgh, PA 15213, United States of America. Electronic address: lewisda@upmc.edu.
University of Pittsburgh · US

Funding

SCHIZOPHRENIA AND CORTICAL DOPAMINE/GABA INTERACTIONSR01MH043784 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 1988 to 2023
$7.2M
Deciphering the GABA neuron alterations in schizophreniaR01MH119701 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FISH, KENNETH N · 2019 to 2023
$2.2M
Request for an Olympus VS200 slide scannerS10MH126905 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FISH, KENNETH N, WATKINS, SIMON C · 2021 to 2021
$370k
Pyramidal neuron hypoactivity in schizophrenia cortexK00MH122943 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCHOONOVER, KIRSTEN · 2019 to 2022
$339k
NIMH NIH HHS K00 MH122943NIMH NIH HHS R01 MH043784NIMH NIH HHS R01 MH119701NIMH NIH HHS S10 MH126905
6 · The paper itself

Abstract

backgroundDorsolateral prefrontal cortex (DLPFC) dysfunction in schizophrenia appears to reflect alterations in layer 3 pyramidal neurons (L3PNs), including smaller cell bodies and lower expression of mitochondrial energy production genes. However, prior somal size studies used biased strategies for identifying L3PNs, and somal size and levels of energy production markers have not been assessed in individual L3PNs. STUDY

designWe combined fluorescent in situ hybridization (FISH) of vesicular glutamate transporter 1 (VGLUT1) mRNA and immunohistochemical-labeling of NeuN to determine if the cytoplasmic distribution of VGLUT1 mRNA permits the unbiased identification and somal size quantification of L3PNs. Dual-label FISH for VGLUT1 mRNA and cytochrome C oxidase subunit 4I1 (COX4I1) mRNA, a marker of energy production, was used to assess somal size and COX4I1 transcript levels in individual DLPFC L3PNs from schizophrenia (12 males; 2 females) and unaffected comparison (13 males; 1 female) subjects. STUDY

resultsMeasures of L3PN somal size with NeuN immunohistochemistry or VGLUT1 mRNA provided nearly identical results (ICC = 0.96, p < 0.0001). Mean somal size of VGLUT1-identified L3PNs was 8.7% smaller (p = 0.004) and mean COX4I1 mRNA levels per L3PN were 16.7% lower (p = 0.01) in schizophrenia. These measures were correlated across individual L3PNs in both subject groups (r

conclusionsThis preliminary study presents a novel method for combining unbiased neuronal identification with quantitative assessments of somal size and mRNA levels. We replicated findings of smaller somal size and lower COX4I1 mRNA levels in DLPFC L3PNs in schizophrenia. The normal scaling of COX4I1 mRNA levels with somal size in schizophrenia suggests that lower markers of energy production are secondary to L3PN morphological alterations in the illness.

Indexed as

SchizophreniaFemaleHumansIn Situ Hybridization, FluorescenceMalePrefrontal CortexPyramidal CellsRNA, MessengerRNA, MessengerCOX4I1Layer 3PostmortemPrefrontal cortexVGLUT1Working memory

Identifiers

PMID38176569
PMCPMC10898364
OpenAlexW4390492635

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.