ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Prefrontal White Matter Structure Mediates the Influence of GAD1 on Working Memory.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- A Systematic Review of Long-Interval Intracortical Inhibition as a Biomarker in Neuropsychiatric Disorders.Frontiers in psychiatry · 2021Pooled it
- A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia.Journal of psychiatry & neuroscience : JPNPooled it
- Executive dysfunction is associated with altered hippocampal-prefrontal functional connectivity in 3xTg Alzheimer's model mice.Communications biology · 2025Article
- miRNA-associated gene networks reveal potential candidate markers for Alzheimer's disease.Frontiers in molecular biosciences · 2025Article
- GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.Frontiers in cellular neuroscience · 2024Review
- TMS-EEG Research to Elucidate the Pathophysiological Neural Bases in Patients with Schizophrenia: A Systematic Review.Journal of personalized medicine · 2021Review
- Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence.Cerebral cortex (New York, N.Y. : 1991) · 2020Article
- COMT and GAD1 gene polymorphisms are associated with impaired antisaccade task performance in schizophrenic patients.European archives of psychiatry and clinical neuroscience · 2018Article
- Toward the Language Oscillogenome.Frontiers in psychology · 2018Article
- A Neural "Tuning Curve" for Multisensory Experience and Cognitive-Perceptual Schizotypy.Schizophrenia bulletin · 2017Article
- Cortical surface-based threshold-free cluster enhancement and cortexwise mediation.Human brain mapping · 2017Article
- The effects of a genome-wide supported variant in the CACNA1C gene on cortical morphology in schizophrenia patients and healthy subjects.Scientific reports · 2016Article
- Bridging the Gap between Genes and Language Deficits in Schizophrenia: An Oscillopathic Approach.Frontiers in human neuroscience · 2016Article
- Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography.Frontiers in neural circuits · 2016Review
- The role of white matter microstructure in inhibitory deficits in patients with schizophrenia.Brain stimulationArticle
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The glutamic acid decarboxylase 1 (GAD1) gene is a major determinant of γ-aminobutyric acid (GABA), the most abundant inhibitory neurotransmitter modulating local neuronal circuitry. GABAergic dysfunction and expression of GAD1 have been implicated in the pathophysiology of schizophrenia, and in working memory impairment. We examined the influence of the functional GAD1 rs3749034 variant on white matter fractional anisotropy (FA), cortical thickness, and working memory performance in schizophrenia patients and healthy controls (N=197). Using transcranial magnetic stimulation with electroencephalography (TMS-EEG), we subsequently examined the effect of rs3749034 on long-interval cortical inhibition (LICI) in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia patients and healthy controls (N=66). We found that the rs3749034 T-allele carrier risk group had lower voxel-wise FA in the prefrontal cortex region (PFWE-corrected<0.05) but not cortical thickness. Mixed-model regression revealed a significant effect on attentional processing and working memory across four performance measures (F1,182=11.5, P=8 × 10(-4)). FA in the prefrontal cortex was associated with digit-span performance. Voxel-wise mediation analysis revealed that the effect GAD1 on poorer digit-span performance statistically predicted the lower white matter FA (PFWE-corrected<0.05). In exploratory analysis, we found a prominent GAD1 genotype-by-diagnosis interaction on DLPFC LICI (F1,56=14.3, P=4.1 × 10(-4)). Our findings converge on variation in GAD1 gene predicting a susceptibility mechanism that affects white matter FA, GABAergic inhibitory neurotransmission in the DLPFC, and working memory performance. Furthermore, via voxel mediation of FA and TMS-EEG intervention, we provide evidence for a potentially causal mechanism through which aberrant DLPFC GABA signaling may contribute to working memory 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.