The impact of nicotinergic modulation on brain excitability, plasticity and cognition in schizophrenia

烟碱能调节对精神分裂症大脑兴奋性、可塑性和认知的影响

• 批准号: 329722408
• 负责人: Professor Dr. Alkomiet Hasan
• 金额: --
• 依托单位: Klinik für Psychiatrie und Psychotherapie (Campus Innenstadt)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/329722408?language=en
• 关键词: impact; nicotinergic; modulation; brain; excitability

Impaired neural plasticity is discussed as one of the most important pathophysiological states underlying schizophrenia. In particular, cognitive deficits occurring at all disease stages and being the main contributors to reduced functionality and poor quality of life, have been linked to this impaired neural plasticity. Physiological investigations provided by the applicant showed the possibility to quantify this impaired motor-cortical plasticity in patients with schizophrenia and these impairments have also been linked to the disease stage, genetic factors and to the smoking status (smoking patients show plasticity, whereas non-smoking patients do not). The latter finding is from particular relevance as up to 75% of all schizophrenia patients smoke. Physiological work from others conducted on healthy subjects displays the possibility to modulate motor-cortical plasticity via targeted nicotinergic stimulation. A systematic evaluation of nicotinergic effects on cortical plasticity and excitability as well on cognition are from the highest importance to improve our understanding of the tremendous high smoking rates in schizophrenia and, moreover, to improve the efficacy of non-invasive brain stimulation in this population. In the first project, the impact of nicotinergic stimulation via alpha4beta2/alpha7 nicotinergic partial/full agonist varenicline on cortical plasticity, excitability and cognition will be investigated. In the second project, a randomized-controlled pilot study to evaluate the efficacy of a combined approach (neurostimulation + nicotinergic stimulation) for the treatment of schizophrenia will be performed (Enhanced Neurostimulation). During this project different physiological techniques (transcranial magnetic stimulation, transcranial direct current stimulation, paired-associative stimulation, surface-electromyography), standardized and operationalized assessments of clinical data and cognitive functions and a certified smoking-withdrawal program will be applied. The pilot-trial will be performed according to the German Drug Law (AMG) and will follow ICH/GCP regulations. These closely interlinked projects will allow for the first time the investigation of the interaction between nicotinergic stimulation and brain plasticity in schizophrenia. This will allow to disentangle the physiological underpinnings of the high rates of tobacco dependency in schizophrenia with regard to the compensatory hypothesis. The pilot-trial represents the first attempt to improve the efficacy of non-invasive brain stimulation for the treatment of schizophrenia by a targeted pharmacological modulation.

神经可塑性受损被讨论为精神分裂症基础的最重要的病理生理状态之一。特别是，在所有疾病阶段出现的认知缺陷，是功能降低和生活质量降低的主要因素，与这种神经可塑性受损有关。申请人提供的生理研究表明，在精神分裂症患者中，有可能量化这种受损的运动皮质可塑性，这些障碍也与疾病阶段，遗传因素和吸烟状态有关（吸烟患者显示可塑性，而非吸烟患者则没有）。后者的发现是特别的相关性，因为所有精神分裂症患者中最多有75％的吸烟。对健康受试者进行的其他人的生理工作表明，通过靶向烟素能刺激调节运动皮质可塑性的可能性。对烟素能对皮质可塑性和兴奋性的影响的系统评估以及认知的兴奋性是最重要的，对于我们对精神分裂症的巨大吸烟率的理解，以及提高非侵入性大脑刺激在该人群中的疗效。在第一个项目中，将研究通过alpha4beta2/alpha7烟碱能局部/完整激动剂的烟灰刺激对皮质可塑性，兴奋性和认知的影响。在第二个项目中，将进行一项随机控制的初步研究，以评估将进行联合方法（神经刺激 +烟碱能刺激）治疗精神分裂症的疗效（增强的神经刺激）。在此项目中，将应用不同的生理技术（经颅磁刺激，经颅直流电流刺激，配对缔合性刺激，表面电骨髓学），对临床数据和认知功能的标准化和操作评估以及认证的吸烟效果。试点审判将根据德国毒品法（AMG）进行，并将遵循ICH/GCP法规。这些紧密相互联系的项目将首次允许对精神分裂症中烟素能刺激与脑可塑性之间的相互作用进行研究。这将允许解散精神分裂症中烟草依赖性高率在补偿性假设方面的生理基础。试验性试验是通过靶向药理调节来提高非侵入性脑刺激治疗精神分裂症的疗效的首次尝试。

项目成果

The two-way relationship between nicotine and cortical activity: a systematic review of neurobiological and treatment aspects

• DOI: 10.1007/s00406-020-01155-6
• 发表时间: 2020-06
• 期刊: European Archives of Psychiatry and Clinical Neuroscience
• 影响因子: 4.7
• 作者: Carlota de Miquel;B. Pross;I. Papazova;Duygu Güler;A. Hasan