Cited by 339Schizophrenia research and treatmentBipolar Disorder and TreatmentNeuroscience and Neuropharmacology Research

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Differential Hippocampal Expression of Glutamic Acid Decarboxylase 65 and 67 Messenger RNA in Bipolar Disorder and Schizophrenia

Heckers, Stephan, Stone, David, Walsh, John, Shick, John, Koul, Pamposh, Benes, Francine M.·2002·Archives of General Psychiatry

DOI 10.1001/archpsyc.59.6.521

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Abstract

BACKGROUND: Expression of messenger RNA (mRNA) for the gamma-aminobutyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase (GAD), in the prefrontal cortex and the number of GABAergic neurons in the hippocampus are reduced in schizophrenia and bipolar disorder. We tested the hypothesis that the expression of the 2 isoforms, one 65 kd (GAD(65)) and the other 67 kd (GAD(67)), is differentially affected in the hippocampus in schizophrenia and bipolar disorder. METHODS: Hippocampal sections from 15 subjects in 3 groups (control subjects and subjects with schizophrenia and bipolar disorder) were studied using an in situ hybridization protocol with sulfur 35-labeled complementary riboprobes for GAD(65) and GAD(67) mRNA. Emulsion-dipped slides were analyzed for the density of GAD mRNA-positive neurons in 4 sectors of the hippocampus and for the cellular expression level of both GAD mRNAs. RESULTS: The density of GAD(65) and GAD(67) mRNA-positive neurons was decreased by 45% and 43%, respectively, in subjects with bipolar disorder, but only 14% and 4%, respectively, in subjects with schizophrenia. The decreased density of GAD(65) mRNA-positive neurons in subjects with bipolar disorder was significant in sectors CA2/3 and dentate gyrus, and that of GAD(67) mRNA-positive neurons was significant in CA4, but not other hippocampal sectors. Cellular GAD(65) mRNA expression was significantly decreased in subjects with bipolar disorder, particularly in CA4, but not in schizophrenic subjects. Cellular GAD(67) mRNA expression was normal in both groups. CONCLUSION: We have found a region-specific deficit of GAD(65) and GAD(67) mRNA expression in bipolar disorder.

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Self-citation
Impaired Recruitment of the Dorsolateral Prefrontal Cortex and Hippocampus During Encoding in Bipolar Disorder
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Authors: Heckers, S., Stone, D., Walsh, J., Shick, J., Koul, P., & Benes, F. M.
Affiliations: McLean Hospital (US)
Corresponding author: Benes, Francine M.
ORCID: Heckers, Stephan
Walsh, John
Benes, Francine M.
Venue: Archives of General Psychiatry
Publisher: American Medical Association (AMA)
Published: 2002-06-01
Volume: 59
Issue: 6
Pages: 521
ISSN: 0003-990X (ISSN-L)
DOI: 10.1001/archpsyc.59.6.521
OpenAlex: W2016712906
Cited by: 322
References: 35
Citations by year: 2026: 2 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 31 · 2020: 9 · 2019: 9 · 2018: 7 · 2017: 8 · 2016: 11 · 2015: 8 · 2014: 16 · 2013: 19 · 2012: 17
FWCI: 11.78
Type: journal article
Language: en
Open access: closed
Locations: Archives of General Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1k23mh001763-01)
National Institute of Mental Health (MH.NS 31862, MH-42261, MH00423, MH31152, MH01763-02)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: GAD65, glutamic acid decarboxylase 67, hippocampus, bipolar disorder, schizophrenia, GABAergic neurons, CA4, dentate gyrus, CA2/3
MeSH terms: Adult, Aged, Bipolar Disorder, Diagnosis, Differential, Female, Glutamate Decarboxylase, Hippocampus, Humans, Isoenzymes, Male, Middle Aged, Neurons, Peptide Fragments, RNA, Messenger, Schizophrenia

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Differential Hippocampal Expression of Glutamic Acid Decarboxylase 65 and 67 Messenger RNA in Bipolar Disorder and Schizophrenia

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