ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2010
Genetic modulation of GABA levels in the anterior cingulate cortex by GAD1 and COMT.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 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
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Functional MRS studies of GABA and glutamate/Glx - A systematic review and meta-analysis.Neuroscience and biobehavioral reviews · 2023Pooled it
- Pooled it
- Downregulation of Mfn2 Contributes to Chronic Postsurgical Pain via Inducing the Pyroptosis of GABAergic Neurons in the Spinal Cord.CNS neuroscience & therapeutics · 2025Article
- Novel pharmacological targets for GABAergic dysfunction in ADHD.Neuropharmacology · 2024Review
- Article
- Reduced Glx and GABA Inductions in the Anterior Cingulate Cortex and Caudate Nucleus Are Related to Impaired Control of Attention in Attention-Deficit/Hyperactivity Disorder.International journal of molecular sciences · 2022Article
- A preliminary genetic association study of GAD1 and GABAB receptor genes in patients with treatment-resistant schizophrenia.Molecular biology reports · 2022Article
- 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
- The relation between parietal GABA concentration and numerical skills.Scientific reports · 2021Article
- The cross-sectional interplay between neurochemical profile and brain connectivity.Human brain mapping · 2021Article
- ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization.European archives of psychiatry and clinical neuroscience · 2021Article
- Effect of Age on GABA+ and Glutathione in a Pediatric Sample.AJNR. American journal of neuroradiology · 2020Article
- Sensorimotor network segregation declines with age and is linked to GABA and to sensorimotor performance.NeuroImage · 2019Article
- Interactive effects of OXTR and GAD1 on envy-associated behaviors and neural responses.PloS one · 2019Article
- Role of gamma-amino-butyric acid in the dorsal anterior cingulate in age-associated changes in cognition.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- GAD65 Promoter Polymorphism rs2236418 Modulates Harm Avoidance in Women via Inhibition/Excitation Balance in the Rostral ACC.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis.European radiology · 2018Article
- Human Occipital and Parietal GABA Selectively Influence Visual Perception of Orientation and Size.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- A methylome-wide mQTL analysis reveals associations of methylation sites with GAD1 and HDAC3 SNPs and a general psychiatric risk score.Translational psychiatry · 2017Article
- Genetic Polymorphism of GABRR2 Modulates Individuals' General Cognitive Ability in Healthy Chinese Han People.Cellular and molecular neurobiology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Gamma-aminobutyric acid (GABA)-ergic transmission is critical for normal cortical function and is likely abnormal in a variety of neuropsychiatric disorders. We tested the in vivo effects of variations in two genes implicated in GABA function on GABA concentrations in prefrontal cortex of living subjects: glutamic acid decarboxylase 1 (GAD1), which encodes GAD67, and catechol-o-methyltransferase (COMT), which regulates synaptic dopamine in the cortex. We studied six single nucleotide polymorphisms (SNPs) in GAD1 previously associated with risk for schizophrenia or cognitive dysfunction and the val158met polymorphism in COMT in 116 healthy volunteers using proton magnetic resonance spectroscopy. Two of the GAD1 SNPs (rs1978340 (p=0.005) and rs769390 (p=0.004)) showed effects on GABA levels as did COMT val158met (p=0.04). We then tested three SNPs in GAD1 (rs1978340, rs11542313, and rs769390) for interaction with COMT val158met based on previous clinical results. In this model, rs11542313 and COMT val158met showed significant main effects (p=0.001 and 0.003, respectively) and a trend toward a significant interaction (p=0.05). Interestingly, GAD1 risk alleles for schizophrenia were associated with higher GABA/Cre, and Val-Val homozygotes had high GABA/Cre levels when on a GAD1 risk genotype background (N=6). These results support the importance of genetic variation in GAD1 and COMT in regulating prefrontal cortical GABA function. The directionality of the effects, however, is inconsistent with earlier evidence of decreased GABA activity in schizophrenia.
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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.