Author:
Morin-Parent Florence,Champigny Camille,Lacroix Angelina,Corbin François,Lepage Jean-François
Abstract
AbstractFragile-X syndrome (FXS) is characterized by neurological and psychiatric problems symptomatic of cortical hyperexcitability. Recent animal studies identified deficient γ-aminobutyricacid (GABA) inhibition as a key mechanism for hyperexcitability in FXS, but the GABA system remains largely unexplored in humans with the disorder. The primary objective of this study was to assess GABA-mediated inhibition and its relationship with hyperexcitability in patients with FXS. Transcranial magnetic stimulation (TMS) was used to assess cortical and corticospinal inhibitory and excitatory mechanisms in 18 patients with a molecular diagnosis of FXS and 18 healthy controls. GABA-mediated inhibition was measured with short-interval intracortical inhibition (GABAA), long-interval intracortical inhibition (GABAB), and the corticospinal silent period (GABAA+B). Net intracortical facilitation involving glutamate was assessed with intracortical facilitation, and corticospinal excitability was measured with the resting motor threshold. Results showed that FXS patients had significantly reduced short-interval intracortical inhibition, increased long-interval intracortical inhibition, and increased intracortical facilitation compared to healthy controls. In the FXS group, reduced short-interval intracortical inhibition was associated with heightened intracortical facilitation. Taken together, these results suggest that reduced GABAA inhibition is a plausible mechanism underlying cortical hyperexcitability in patients with FXS. These findings closely match those observed in animal models, supporting the translational validity of these markers for clinical research.
Publisher
Springer Science and Business Media LLC
Subject
Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry and Mental health
Cited by
31 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献