ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 2 of them syntheses that pooled it.
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Who cites it
180 citing papers in PubMed, 2 syntheses or guidelines pooled it, 320 citations in OpenAlex.
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- Prenatal Primary Prevention of Mental Illness by Micronutrient Supplements in Pregnancy.The American journal of psychiatry · 2018Pooled it
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- Memantine Effects on Electroencephalographic Measures of Putative Excitatory/Inhibitory Balance in Schizophrenia.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2020Trial
- Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk.The American journal of psychiatry · 2013Trial
- Transcriptomics and proteomics of projection neurons in a circuit linking hippocampus with dorsolateral prefrontal cortex in the human brain.bioRxiv : the preprint server for biology · 2026Article
- Temporal and cell-type specific SPAK-NKCC1 disruption following severe TBI in the developing gyrencephalic brain.Acta neuropathologica communications · 2026Article
- Plasma KCC2, NKCC1, and GABA as peripheral biomarkers in autism spectrum disorder: a combined ROC analysis.Metabolic brain disease · 2026Article
- Synthesis of new sulfoximines and sulfonimidamides derivatives as NKCC1 inhibitors.Frontiers in chemistry · 2026Article
- Matching developmental timelines of fish, frog, mouse and human brains.Animal cells and systems · 2026Review
- The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders.International journal of molecular sciences · 2025Review
- Long-read sequencing reveals the RNA isoform repertoire of neuropsychiatric risk genes in human brain.Genome biology · 2025Article
- The Causal Relationships Between Inflammatory Proteins, Brain Structure, and Psychiatric Disorders: A Two-Step Mendelian Randomization Analysis.Schizophrenia bulletin · 2025Article
- Biophysical characterization and ion transport with cell-based and proteoliposome reconstitution assays of invertebrate KFEBS open bio · 2025Article
- Alterations in Prefrontal Cortical Somatostatin Neurons in Schizophrenia: Evidence for Weaker Inhibition of Pyramidal Neuron Dendrites.Biological psychiatry · 2025Article
- Targeting the Roots of Psychosis: The Role of Aberrant Salience.Pediatric reports · 2025Review
- Developmental dynamics of marmoset prefrontal cortical SST and PV interneuron networks highlight primate-specific features.Development (Cambridge, England) · 2025Article
- Large-scale transcriptomic analyses of major depressive disorder reveal convergent dysregulation of synaptic pathways in excitatory neurons.Nature communications · 2025Article
- Reduced temporal variability of cortical excitation/inhibition ratio in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2025Article
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120 more citing papers are in PubMed but not listed here.
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13 authors at 1 institution in 1 country.
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Abstract
GABA signaling molecules are critical for both human brain development and the pathophysiology of schizophrenia. We examined the expression of transcripts derived from three genes related to GABA signaling [GAD1 (GAD67 and GAD25), SLC12A2 (NKCC1), and SLC12A5 (KCC2)] in the prefrontal cortex (PFC) and hippocampal formation of a large cohort of nonpsychiatric control human brains (n = 240) across the lifespan (from fetal week 14 to 80 years) and in patients with schizophrenia (n = 30-31), using quantitative RT-PCR. We also examined whether a schizophrenia risk-associated promoter SNP in GAD1 (rs3749034) is related to expression of these transcripts. Our studies revealed that development and maturation of both the PFC and hippocampal formation are characterized by progressive switches in expression from GAD25 to GAD67 and from NKCC1 to KCC2. Previous studies have demonstrated that the former leads to GABA synthesis, and the latter leads to switching from excitatory to inhibitory neurotransmission. In the hippocampal formation, GAD25/GAD67 and NKCC1/KCC2 ratios are increased in patients with schizophrenia, reflecting a potentially immature GABA physiology. Remarkably, GAD25/GAD67 and NKCC1/KCC2 expression ratios are associated with rs3749034 genotype, with risk alleles again predicting a relatively less mature pattern. These findings suggest that abnormalities in GABA signaling critical to brain development contribute to genetic risk for schizophrenia.
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