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Cited by 53Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchAmino Acid Enzymes and Metabolism

Lower Glutamic Acid Decarboxylase 65-kDa Isoform Messenger RNA and Protein Levels in the Prefrontal Cortex in Schizoaffective Disorder but Not Schizophrenia

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Glausier, Jill R., Kimoto, Sohei, Fish, Kenneth N., Lewis, David A.·2015·Biological Psychiatry
DOI 10.1016/j.biopsych.2014.05.010PMC PMC4247819
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Abstract

Background Altered gamma-aminobutyric acid (GABA) signaling in the prefrontal cortex (PFC) has been associated with cognitive dysfunction in patients with schizophrenia and schizoaffective disorder. Levels of the GABA-synthesizing enzyme glutamic acid decarboxylase 67-kDa isoform (GAD67) in the PFC have been consistently reported to be lower in patients with these disorders, but the status of the second GABA-synthesizing enzyme, glutamic acid decarboxylase 65-kDa isoform (GAD65), remains unclear.Methods GAD65 messenger RNA (mRNA) levels were quantified in PFC area 9 by quantitative polymerase chain reaction from 62 subjects with schizophrenia or schizoaffective disorder and 62 matched healthy comparison subjects. In a subset of subject pairs, GAD65 relative protein levels were quantified by confocal immunofluorescence microscopy.Results Mean GAD65 mRNA levels were 13.6% lower in subjects with schizoaffective disorder but did not differ in subjects with schizophrenia relative to their matched healthy comparison subjects. In the subjects with schizoaffective disorder, mean GAD65 protein levels were 19.4% lower and were correlated with GAD65 mRNA levels. Lower GAD65 mRNA and protein levels within subjects with schizoaffective disorder were not attributable to factors commonly comorbid with the diagnosis.Conclusions In concert with previous studies, these findings suggest that schizoaffective disorder is associated with lower levels of both GAD65 and GAD67 mRNA and protein in the PFC, whereas subjects with schizophrenia have lower mean levels of only GAD67 mRNA and protein. Because cognitive function is generally better preserved in patients with schizoaffective disorder relative to patients with schizophrenia, these findings may support an interpretation that GAD65 downregulation provides a homeostatic response complementary to GAD67 downregulation that serves to reduce inhibition in the face of lower PFC network activity.

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  • Paired and unpaired ANCOVA models both assessed diagnosis effects on each dependent variable; the paired model supplied reported values since the two models agreed except where noted.

    “Two analyses of covariance (ANCOVA) models (paired and unpaired) were used as described previously (Glausier et al, 2015) to test the effect of diagnosis on each dependent variable.All reported values are from the paired ANCOVA as both models yielded similar results (except where noted in the text).”

    From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Glausier et al, 2015

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  1. [54]American Psychiatric Association DSM-IV. Diagnostic and Statistical Manual of Mental Disorders 1994 Fourth Edition. Washington, D.C. American Psychiatric Association

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Authors
Glausier, J. R., Kimoto, S., Fish, K. N., & Lewis, D. A.
Affiliations
University of Pittsburgh (US)
Corresponding author
Lewis, David A.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2015-01
Volume
77
Issue
2
Pages
167-176
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2014.05.010
PMC
PMC4247819
OpenAlex
W2070767341
Cited by
53
References
88
Citations by year
2026: 3 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 10 · 2015: 11 · 2014: 1
FWCI
6.11
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (MH043784, MH096985)
  • Nara Medical University
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 › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
GAD65, GAD67, prefrontal cortex, schizoaffective disorder, schizophrenia, GABA synthesis, GABA signaling, cognitive impairment, gene expression, protein abundance, homeostatic responses
MeSH terms
Female, Glutamate Decarboxylase, Humans, Immunohistochemistry, Male, Microscopy, Fluorescence, Middle Aged, Psychotic Disorders, RNA, Messenger, Schizophrenia, Cohort Studies, Polymerase Chain Reaction, Prefrontal Cortex, Microscopy, Confocal

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