ArticleThe American journal of psychiatry2014
Lower expression of glutamic acid decarboxylase 67 in the prefrontal cortex in schizophrenia: contribution of altered regulation by Zif268.
Article in The American journal of psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 91 citations in OpenAlex.
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- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- Egr1 is a sex-dependent regulator of neuronal chromatin, structural plasticity, and behaviour.Nature communications · 2025Article
- Memory-Associated Immediate Early Genes: Roles in Synaptic Function, Memory Processes, and Neurological Diseases.Molecular neurobiology · 2025Review
- Transcriptional Regulators in the Cerebellum in Chronic Schizophrenia: Novel Possible Targets for Pharmacological Interventions.International journal of molecular sciences · 2025Article
- Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia.Molecular psychiatry · 2025Review
- Prefrontal cortical circuits in social behaviors: an overview.Journal of Zhejiang University. Science. B · 2024Review
- GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.Frontiers in cellular neuroscience · 2024Review
- Early- and late-phase changes of brain activity and early-phase neuromodulation in the posttraumatic stress disorder rat model.Neurobiology of stress · 2023Article
- Localization and Diagnostic Specificity of Glutamic Acid Decarboxylase Transcript Alterations in the Dorsolateral Prefrontal Cortex in Schizophrenia.Biological psychiatry · 2023Article
- Sex linked behavioral and hippocampal transcriptomic changes in mice with cell-type specificFrontiers in neuroscience · 2023Article
- Intraneuronal accumulation of amyloid-β peptides as the pathomechanism linking autism and its co-morbidities: epilepsy and self-injurious behavior - the hypothesis.Frontiers in molecular neuroscience · 2023Article
- Beyond the γ-aminobutyric acid hypothesis of schizophrenia.Frontiers in cellular neuroscience · 2023Review
- Targeting histone demethylase LSD1 for treatment of deficits in autism mouse models.Molecular psychiatry · 2022Article
- Abnormal synaptic plasticity and impaired cognition in schizophrenia.World journal of psychiatry · 2022Review
- In vivo study sheds new light on the dendritic spine pathology hypothesis of schizophrenia.Molecular psychiatry · 2022Article
- Mechanisms underlying dorsolateral prefrontal cortex contributions to cognitive dysfunction in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Review
- Pharmacological Treatment for Social Cognition: Current Evidence.International journal of molecular sciences · 2021Review
- Maternal Deprivation in Rats Decreases the Expression of Interneuron Markers in the Neocortex and Hippocampus.Frontiers in neuroanatomy · 2021Article
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3 authors at 1 institution in 1 country.
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Abstract
objectiveCognitive deficits of schizophrenia may be due at least in part to lower expression of the 67-kDa isoform of glutamic acid decarboxylase (GAD67), a key enzyme for GABA synthesis, in the dorsolateral prefrontal cortex of individuals with schizophrenia. However, little is known about the molecular regulation of lower cortical GAD67 levels in schizophrenia. The GAD67 promoter region contains a conserved Zif268 binding site, and Zif268 activation is accompanied by increased GAD67 expression. Thus, altered expression of the immediate early gene Zif268 may contribute to lower levels of GAD67 mRNA in the dorsolateral prefrontal cortex in schizophrenia.
methodThe authors used polymerase chain reaction to quantify GAD67 and Zif268 mRNA levels in dorsolateral prefrontal cortex area 9 from 62 matched pairs of schizophrenia and healthy comparison subjects, and in situ hybridization to assess Zif268 expression at laminar and cellular levels of resolution. The effects of potentially confounding variables were assessed in human subjects, and the effects of antipsychotic treatments were tested in antipsychotic-exposed monkeys. The specificity of the Zif268 findings was assessed by quantifying mRNA levels for other immediate early genes.
resultsGAD67 and Zif268 mRNA levels were significantly lower and were positively correlated in the schizophrenia subjects. Both Zif268 mRNA-positive neuron density and Zif268 mRNA levels per neuron were significantly lower in the schizophrenia subjects. These findings were robust to the effects of the confounding variables examined and differed from other immediate early genes.
conclusionsDeficient Zif268 mRNA expression may contribute to lower cortical GAD67 levels in schizophrenia, suggesting a potential mechanistic basis for altered cortical GABA synthesis and impaired cognition in schizophrenia.
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