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Hyperexcitability and impaired intracortical inhibition in patients with fragile-X syndrome.
Translational Psychiatry ( IF 5.8 ) Pub Date : 2019-11-20 , DOI: 10.1038/s41398-019-0650-z Florence Morin-Parent 1, 2 , Camille Champigny 2, 3 , Angelina Lacroix 1, 2 , François Corbin 2, 3 , Jean-François Lepage 1, 2
Translational Psychiatry ( IF 5.8 ) Pub Date : 2019-11-20 , DOI: 10.1038/s41398-019-0650-z Florence Morin-Parent 1, 2 , Camille Champigny 2, 3 , Angelina Lacroix 1, 2 , François Corbin 2, 3 , Jean-François Lepage 1, 2
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Fragile-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.
中文翻译：
脆性X综合征患者的过度兴奋和皮质内抑制受损。
脆性X综合征（FXS）的特征是皮质兴奋过度的神经系统和精神病学症状。最近的动物研究发现，缺乏γ-氨基丁酸（GABA）抑制作用是FXS过度兴奋的关键机制，但是在患有这种疾病的人中，GABA系统仍未开发。这项研究的主要目的是评估FXS患者中GABA介导的抑制作用及其与过度兴奋性的关系。经颅磁刺激（TMS）用于评估18名具有FXS分子诊断的患者和18名健康对照的皮质和皮质脊髓抑制和兴奋机制。用短间隔皮质内抑制（GABAA），长间隔皮质内抑制（GABAB）和皮质脊髓静默期（GABAA + B）测量GABA介导的抑制。用皮层内促进评估涉及谷氨酸的净皮层内促进，并用静止运动阈值测量皮质脊髓兴奋性。结果显示，与健康对照组相比，FXS患者的短间隔皮质内抑制明显减少，长间隔皮质内抑制增加，并且皮质内促进作用增强。在FXS组中，短间隔皮质内抑制的减少与皮质内促进的增强相关。综上所述，这些结果表明，降低的GABAA抑制作用是FXS患者皮质过度兴奋性的潜在机制。这些发现与在动物模型中观察到的结果非常匹配，从而支持了这些标记物在临床研究中的翻译有效性。
更新日期：2019-11-20
中文翻译：
脆性X综合征患者的过度兴奋和皮质内抑制受损。
脆性X综合征（FXS）的特征是皮质兴奋过度的神经系统和精神病学症状。最近的动物研究发现，缺乏γ-氨基丁酸（GABA）抑制作用是FXS过度兴奋的关键机制，但是在患有这种疾病的人中，GABA系统仍未开发。这项研究的主要目的是评估FXS患者中GABA介导的抑制作用及其与过度兴奋性的关系。经颅磁刺激（TMS）用于评估18名具有FXS分子诊断的患者和18名健康对照的皮质和皮质脊髓抑制和兴奋机制。用短间隔皮质内抑制（GABAA），长间隔皮质内抑制（GABAB）和皮质脊髓静默期（GABAA + B）测量GABA介导的抑制。用皮层内促进评估涉及谷氨酸的净皮层内促进，并用静止运动阈值测量皮质脊髓兴奋性。结果显示，与健康对照组相比，FXS患者的短间隔皮质内抑制明显减少，长间隔皮质内抑制增加，并且皮质内促进作用增强。在FXS组中，短间隔皮质内抑制的减少与皮质内促进的增强相关。综上所述，这些结果表明，降低的GABAA抑制作用是FXS患者皮质过度兴奋性的潜在机制。这些发现与在动物模型中观察到的结果非常匹配，从而支持了这些标记物在临床研究中的翻译有效性。
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