ArticleMolecular psychiatry2007
Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression.
Article in Molecular psychiatry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01237158 (Genetic Association Study Between GAD1 and Reelin Polymorphisms and GABA/Glutamate MRS in Bipolar Disorder Type 1 and Healthy Controls), which is not on this map. Cited by 140 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Genetic Association Study Between GAD1 and Reelin Polymorphisms and GABA/Glutamate MRS in Bipolar Disorder Type 1 and Healthy Controls: SPECGENE PROJECT
Who cites it
140 citing papers in PubMed, 276 citations in OpenAlex.
- Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia.The American journal of psychiatry · 2008Trial
- GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss.Molecular psychiatry · 2005Trial
- Glial-neuronal crosstalk via GABA signaling: mechanistic insights into neuropsychiatric and neurological pathophysiology.Molecular psychiatry · 2026Review
- The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders.International journal of molecular sciences · 2025Review
- Schizophrenia-Like Deficits and Impaired Glutamate/Gamma-aminobutyric acid Homeostasis in Zfp804a Conditional Knockout Mice.Schizophrenia bulletin · 2024Article
- Advances in the study of phencyclidine-induced schizophrenia-like animal models and the underlying neural mechanisms.Schizophrenia (Heidelberg, Germany) · 2024Review
- 40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by Gabaergic Neuronal Inhibition.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Epigenetic Regulation in Schizophrenia: Focus on Methylation and Histone Modifications in Human Studies.Genes · 2024Review
- GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.Frontiers in cellular neuroscience · 2024Review
- Article
- Localization and Diagnostic Specificity of Glutamic Acid Decarboxylase Transcript Alterations in the Dorsolateral Prefrontal Cortex in Schizophrenia.Biological psychiatry · 2023Article
- Article
- Developmental and epileptic encephalopathy 89: A novel bi-allelic variant, molecular dynamics simulation, and a comprehensive clinical and molecular profile.Epilepsia open · 2023Article
- Cortical interneurons in schizophrenia - cause or effect?Croatian medical journal · 2023Review
- Beyond the γ-aminobutyric acid hypothesis of schizophrenia.Frontiers in cellular neuroscience · 2023Review
- Cognitive Dysfunction and Prefrontal Cortical Circuit Alterations in Schizophrenia: Developmental Trajectories.Biological psychiatry · 2022Review
- A preliminary genetic association study of GAD1 and GABAB receptor genes in patients with treatment-resistant schizophrenia.Molecular biology reports · 2022Article
- An alternative splicing hypothesis for neuropathology of schizophrenia: evidence from studies on historical candidate genes and multi-omics data.Molecular psychiatry · 2022Review
- Microglia as a Hub for Suicide Neuropathology: Future Investigation and Prevention Targets.Frontiers in cellular neuroscience · 2022Review
- Interacting Roles of COMT and GAD1 Genes in Patients with Treatment-Resistant Schizophrenia: a Genetic Association Study of Schizophrenia Patients and Healthy Controls.Journal of molecular neuroscience : MN · 2021Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Cortical GABAergic dysfunction has been implicated as a key component of the pathophysiology of schizophrenia and decreased expression of the gamma-aminobutyric acid (GABA) synthetic enzyme glutamic acid decarboxylase 67 (GAD(67)), encoded by GAD1, is found in schizophrenic post-mortem brain. We report evidence of distorted transmission of single-nucleotide polymorphism (SNP) alleles in two independent schizophrenia family-based samples. In both samples, allelic association was dependent on the gender of the affected offspring, and in the Clinical Brain Disorders Branch/National Institute of Mental Health (CBDB/NIMH) sample it was also dependent on catechol-O-methyltransferase (COMT) Val158Met genotype. Quantitative transmission disequilibrium test analyses revealed that variation in GAD1 influenced multiple domains of cognition, including declarative memory, attention and working memory. A 5' flanking SNP affecting cognition in the families was also associated in unrelated healthy individuals with inefficient BOLD functional magnetic resonance imaging activation of dorsal prefrontal cortex (PFC) during a working memory task, a physiologic phenotype associated with schizophrenia and altered cortical inhibition. In addition, a SNP in the 5' untranslated (and predicted promoter) region that also influenced cognition was associated with decreased expression of GAD1 mRNA in the PFC of schizophrenic brain. Finally, we observed evidence of statistical epistasis between two SNPs in COMT and SNPs in GAD1, suggesting a potential biological synergism leading to increased risk. These coincident results implicate GAD1 in the etiology of schizophrenia and suggest that the mechanism involves altered cortical GABA inhibitory activity, perhaps modulated by dopaminergic function.
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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.