脑源性神经营养因子Val66Met多态性对精神分裂症患者皮质可塑性的影响：一项概念验证研究。
BDNF-Val66Met-polymorphism impact on cortical plasticity in schizophrenia patients: a proof-of-concept study.
作者信息
Strube Wolfgang, Nitsche Michael A, Wobrock Thomas, Bunse Tilmann, Rein Bettina, Herrmann Maximiliane, Schmitt Andrea, Nieratschker Vanessa, Witt Stephanie H, Rietschel Marcella, Falkai Peter, Hasan Alkomiet
机构信息
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany (Dr Strube, Bunse, Schmitt, Falkai, and Hasan); Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany (Dr Nitsche); Centre of Mental Health, Darmstadt-Dieburg Clinics, Groß-Umstadt, Germany (Dr Wobrock); Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (Drs Wobrock, Rein, and Herrmann); Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of São Paulo, São Paulo, Brazil (Dr Schmitt); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim Medical Faculty Mannheim/Heidelberg University, Germany and Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany (Dr Nieratschker); Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany (Drs Witt and Rietschel).
出版信息
Int J Neuropsychopharmacol. 2014 Oct 31;18(4):pyu040. doi: 10.1093/ijnp/pyu040.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients.
METHODS
Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied.
RESULTS
Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS.
CONCLUSIONS
These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory intracortical interneuron-networks, cortical plasticity, and the BDNF-Val66Met-polymorphism. Further replication and validation need to be dedicated to this question to confirm this relationship.
背景
脑源性神经营养因子（BDNF）已被证明是神经可塑性的调节因子。一种常见的BDNF多态性（Val66Met）与皮质可塑性受损有关。在精神分裂症患者中，非侵入性脑刺激后神经可塑性反应降低的情况已得到一致报道。各种研究表明，BDNF-Val66Met多态性与健康个体的运动皮质可塑性之间存在关联，但尚未对精神分裂症患者进行研究。因此，本概念验证研究的目的是测试BDNF-Val66Met多态性对精神分裂症患者抑制性和易化性皮质可塑性的影响。
方法
对22例精神分裂症患者和35名健康对照者使用阳极和阴极经颅直流电刺激（tDCS）施加于左侧初级运动皮质，研究皮质可塑性。动物和人体研究表明，阳极和阴极tDCS后的兴奋性变化与分子长期增强和长期抑制有关。为了测试tDCS前后的运动皮质兴奋性，应用了成熟的单脉冲和双脉冲经颅磁刺激方案。
结果
我们的分析显示，在基线时，与缬氨酸纯合子相比，蛋氨酸杂合子中谷氨酸介导的皮质内易化增加。阴极tDCS后，精神分裂症蛋氨酸杂合子中γ-氨基丁酸介导的短间隔皮质内抑制降低，而健康蛋氨酸杂合子则表现出相反的效果。BDNF-Val66Met多态性不影响tDCS后单脉冲运动诱发电位的幅度。
结论
这些初步发现支持了BDNF-Val66Met多态性与精神分裂症患者阴极tDCS后可塑性的可观察到的改变之间存在关联的观点。这表明抑制性皮质内中间神经元网络、皮质可塑性和BDNF-Val66Met多态性之间存在复杂的相互作用。需要进一步重复和验证来证实这种关系。
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