CoChat
Sign Up
Cited by 1,002Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics.

Akbarian, Schahram·1995·Archives of General Psychiatry
DOI 10.1001/archpsyc.1995.03950160008002
Open this paper in CoChat — free account

Abstract

Background: Up-regulation of γ-aminobutyric acidA(GABAA) receptors and decreased GABA uptake in the cerebral cortex of schizophrenics suggest altered GABAergic transmission, which could be caused by primary disturbance of GABA synapses or by decreased production of the transmitter. Decreased production could be due to a shutdown in GABA production or to loss of GABA neurons caused by cell death or their failure to migrate to the cortex during brain development. Methods: To discriminate between these possibilities, we quantified levels of messenger RNA (mRNA) for the 67-kd isoform of glutamic acid decarboxylase (GAD), the key enzyme in GABA synthesis, and the number and laminar distribution of GAD mRNA-expressing neurons in the dorsolateral prefrontal cortex (DLPFC) of schizophrenics and matched controls, using in situ hybridization-histochemistry, densitometry, and cell-counting methods. These data were compared with the total number of neurons, the number of small, round or ovoid neurons 8 to 15 µm in diameter, and overall frontal lobe volume. As a control, mRNA levels for type II calciumcalmodulin-dependent protein kinase (CamIIK) were quantified. Results: Schizophrenics showed a pronounced decrease in GAD mRNA levels in neurons of layer I (40%) and layer II (48%) and an overall 30% decrease in layers III to VI. There were also strong overall reductions in GAD mRNA levels. The CamIIK mRNA levels showed no significant differences between samples. No differences were found in the total number of neurons nor in small, round or ovoid neurons, which should include a majority of the GABA cells. Prefrontal gray and white matter volume did not differ significantly between controls and schizophrenics. The prefrontal cortex of schizophrenics shows reduced expression for GAD in the absence of significant cell loss. This may be brought about by an activitydependent down-regulation associated with the functional hypoactivity of the DLPFC. The lack of significant alterations in cell numbers in the DLPFC and frontal lobe volume in schizophrenics also implies that overall cortical neuronal migration had not been compromised in development. Previous reports of altered neuronal distribution in the subcortical white matter of schizophrenic brains in comparison with that of controls may indicate disturbances of migration or programmed cell death in the cortical subplate, leading to altered connection formation in the overlying cortex of schizophrenics and activity-dependent down-regulation of neurotransmitter-related gene expression. Conclusions: The prefrontal cortex of schizophrenics shows reduced expression for GAD in the absence of significant cell loss. This may be brought about by an activity dependent down-regulation associated with the functional hypoactivity of the DLPFC. The lack of significant alterations in cell numbers in the DLPFC and frontal lobe volume in schizophrenics also implies that overall cortical neuronal migration had not been compromised in development. Previous reports of altered neuronal distribution in the subcortical white matter of schizophrenic brains in comparison with that of controls may indicate disturbances of migration or programmed cell death in the cortical subplate, leading to altered connection formation in the overlying cortex of schizophrenics and activity-dependent down-regulation of neurotrans mitter-related gene expression.

Integrity signals

Registry

Crossref · 10.1001/archpsyc.1995.03950160008002

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Post-mortem brain tissues from schizophrenia patients exhibit reduced PV and/or GAD67 mRNA, particularly in prefrontal cortex.

    “In situ hybridization and RT-PCR studies indicate that post-mortem brain tissues from schizophrenia patients exhibit reduced PV and/or GAD67 mRNA, particularly in prefrontal cortex (Akbarian et al., 1995; Volk et al., 2000; Hashimoto et al., 2003, 2008a,b; Mellios et al., 2009).”

    From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Akbarian et al., 1995

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Akbarian, S.
Affiliations
University of California, Irvine (US)
Corresponding author
Akbarian, Schahram
ORCID
Akbarian, Schahram
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
1995-04-01
Volume
52
Issue
4
Pages
258
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archpsyc.1995.03950160008002
OpenAlex
W2156026059
Cited by
1,002
References
49
Citations by year
2026: 8 · 2025: 8 · 2024: 15 · 2023: 12 · 2022: 15 · 2021: 22 · 2020: 32 · 2019: 36 · 2018: 19 · 2017: 32 · 2016: 38 · 2015: 51 · 2014: 49 · 2013: 43 · 2012: 47
FWCI
24.55
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5p50mh044188-05)
  • National Institute of Mental Health (MH44188)
  • National Institute of Neurological Disorders and Stroke (NS21377, R01NS021377)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
schizophrenia, glutamic acid decarboxylase, GABA synthesis, dorsolateral prefrontal cortex, GABAergic neurotransmission, GABA receptors, GABA uptake, neuronal loss, cortical laminar distribution, neuronal migration, frontal lobe volume, gene expression, frontal lobe development
MeSH terms
Adult, Aged, Autoradiography, Cell Count, Densitometry, Female, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Humans, Male, Middle Aged, Neurons, RNA, Messenger, Schizophrenia, Down-Regulation, Gene Expression, Cell Death, Prefrontal Cortex, In Situ Hybridization, Age of Onset, Receptors, GABA

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review