Korostenskaja M, Kähkönen S
Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Curr Pharm Des. 2009;15(22):2573-93. doi: 10.2174/138161209788957474.
Cognitive dysfunction is considered to be a core feature in schizophrenia. It is believed that antipsychotic drugs, especially atypical ones, could improve cognitive functions in schizophrenia patients. Auditory event-related potentials (ERPs) such as mismatch negativity (MMN) and P300 response are potential candidates for objective investigation of pre-attentional and attention-dependent processing in schizophrenia patients, respectively. Both these responses were found to be altered in schizophrenia. Moreover, neurotransmitters play important role in generation of MMN and P300 components. Therefore, these ERPs are potential candidates for monitoring the cognitive changes caused by neurochemical modulation during antipsychotic treatment in schizophrenia patients. In addition, neurochemical ERP generation mechanisms discovered during drug-challenge studies in healthy subjects could explain these ERP findings in patients. To date, no effect of antipsychotic treatment on MMN was observed, whereas certain antipsychotics (e.g. clozapine) could modulate P300 response. At the same time, adjunctive glutamate-system affecting therapy seems to influence MMN response. The explanation of these phenomena could be a weak relationship between dopaminergic activities and MMN response and a strong connection between glutamate NMDA receptors and MMN generation. As to the P300 component, because of the multiple generators, it is more sensitive to the influences of different neurochemical activities. In the future, the combination of transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) with electroencephalography (EEG) will open new possibilities for understanding the drug-induced changes on the neural substrates of information processing in schizophrenia patients.
认知功能障碍被认为是精神分裂症的核心特征。人们认为抗精神病药物，尤其是非典型抗精神病药物，可以改善精神分裂症患者的认知功能。听觉事件相关电位（ERP），如失配负波（MMN）和P300反应，分别是客观研究精神分裂症患者前注意和注意依赖加工的潜在指标。研究发现，这两种反应在精神分裂症中均发生改变。此外，神经递质在MMN和P300成分的产生中起重要作用。因此，这些ERP是监测精神分裂症患者抗精神病治疗期间神经化学调节引起的认知变化的潜在指标。此外，在健康受试者的药物激发研究中发现的神经化学ERP产生机制可以解释患者的这些ERP结果。迄今为止，未观察到抗精神病治疗对MMN有影响，而某些抗精神病药物（如氯氮平）可以调节P300反应。同时，辅助性影响谷氨酸系统的治疗似乎会影响MMN反应。对这些现象的解释可能是多巴胺能活动与MMN反应之间的关系较弱，而谷氨酸NMDA受体与MMN产生之间的联系较强。至于P300成分，由于其有多个发生器，它对不同神经化学活动的影响更敏感。未来，经颅磁刺激（TMS）和功能磁共振成像（fMRI）与脑电图（EEG）的结合将为理解精神分裂症患者信息处理神经基质上的药物诱导变化开辟新的可能性。
