ArticleProceedings of the National Academy of Sciences of the United States of America2007
Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 247 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
247 citing papers in PubMed, 4 syntheses or guidelines pooled it, 483 citations in OpenAlex.
- A systematic review and meta-analysis of the auditory steady-state response in schizophrenia, bipolar disorder, and autism spectrum disorder.Molecular psychiatry · 2026Pooled it
- Hippocampal subregion abnormalities in schizophrenia: A systematic review of structural and physiological imaging studies.Neuropsychopharmacology reports · 2018Pooled it
- Neuroimaging studies of GABA in schizophrenia: a systematic review with meta-analysis.Translational psychiatry · 2017Pooled it
- Systematic review of genome-wide gene expression studies of bipolar disorder.BMC psychiatry · 2013Pooled it
- Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Trial
- PET neuroimaging reveals histone deacetylase dysregulation in schizophrenia.The Journal of clinical investigation · 2019Trial
- Trial
- Evaluating neurochemical changes and associated locomotor activity in a double hit schizophrenia model.IBRO neuroscience reports · 2026Article
- Novel positive allosteric modulators of alpha 5 subunit-containing GABASchizophrenia research · 2026Article
- Targeting the SIRT1-NAT10-GABABR1 Axis: A Novel Epitranscriptomic Approach to Mitigate Sevoflurane-Induced Cognitive Impairment in Aging.CNS neuroscience & therapeutics · 2026Article
- Can Sodium Oxybate Mitigate the Symptoms of Schizophrenia?Current neuropharmacology · 2026Review
- Remimazolam-Induced Paradoxical Reaction in a Bipolar Patient: A Case Report.Clinical case reports · 2025Article
- Epigenetics and Gut Microbiota in the Pathogenesis and Treatment of Bipolar Disorder (BD).Cells · 2025Review
- Targeting GABAergic Hypofunction Associated with Schizophrenia: Identification of α1β2γ2GABA-A Receptor Ligands with Neuroprotective and Antipsychotic Properties.ACS chemical neuroscience · 2025Article
- Linking Mitochondrial Dysfunction, Neurotransmitter, and Neural Network Abnormalities and Mania: Elucidating Neurobiological Mechanisms of the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Review
- Disruption of the gut microbiota-inflammation-brain axis in unmedicated bipolar disorder II depression.Translational psychiatry · 2024Article
- Single-cell multi-cohort dissection of the schizophrenia transcriptome.Science (New York, N.Y.) · 2024Article
- Knockdown of Lhx6 during embryonic development results in neurophysiological alterations and behavioral deficits analogous to schizophrenia in adult rats.Schizophrenia research · 2024Article
- Identification of the Shared Gene Signatures Between Alzheimer's Disease and Diabetes-Associated Cognitive Dysfunction by Bioinformatics Analysis Combined with Biological Experiment.Journal of Alzheimer's disease : JAD · 2024Article
- The genomic landscape of mammal domestication might be orchestrated by selected transcription factors regulating brain and craniofacial development.Development genes and evolution · 2023Article
187 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
GABAergic dysfunction is present in the hippocampus in schizophrenia (SZ) and bipolar disorder (BD). The trisynaptic pathway was "deconstructed" into various layers of sectors CA3/2 and CA1 and gene expression profiling performed. Network association analysis was used to uncover genes that may be related to regulation of glutamate decarboxylase 67 (GAD(67)), a marker for this system that has been found by many studies to show decreased expression in SZs and BDs. The most striking change was a down-regulation of GAD(67) in the stratum oriens (SO) of CA2/3 in both groups; CA1 only showed changes in the SO of schizophrenics. The network generated for GAD(67) contained 25 genes involved in the regulation of kainate receptors, TGF-beta and Wnt signaling, as well as transcription factors involved in cell growth and differentiation. In SZs, IL-1beta, (GRIK2/3), TGF-beta2, TGF-betaR1, histone deacetylase 1 (HDAC1), death associated protein (DAXX), and cyclin D2 (CCND2) were all significantly up-regulated, whereas in BDs, PAX5, Runx2, LEF1, TLE1, and CCND2 were significantly down-regulated. In the SO of CA1 of BDs, where GAD67 showed no expression change, TGF-beta and Wnt signaling genes were all up-regulated, but other transcription factors showed no change in expression. In other layers/sectors, BDs showed no expression changes in these GAD(67) network genes. Overall, these results are consistent with the hypothesis that decreased expression of GAD(67) may be associated with an epigenetic mechanism in SZ. In BD, however, a suppression of transcription factors involved in cell differentiation may contribute to GABA dysfunction.
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Registered trials
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.