Hajós Mihály
Neuroscience Department, CNS Discovery, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.
Trends Pharmacol Sci. 2006 Jul;27(7):391-8. doi: 10.1016/j.tips.2006.05.005.
Current observations indicate that dysfunction of neuronal circuitry dynamics contributes to the abnormal information processing in the brain in schizophrenia. It is presumed that disrupted auditory gating, abnormal P300-evoked potentials and deficits in mismatch negativity in schizophrenic patients indicate impaired processing of information. Recently, abnormalities in neuronal synchrony and oscillatory activity have been postulated as the mechanisms that underlie the distorted perception and cognitive dysfunction associated with schizophrenia. These novel observations might reveal the pathophysiology of the disorder, and indicate potential targets for antipsychotic drug therapy. Neuronal circuitry dynamics, such as network oscillations and sensory-gating processes, are conserved phylogenetically, which provides excellent opportunities for designing translational biomarkers. Whether preclinical, experimental compounds that impact on network oscillations and sensory processing (such as agonists and modulators of alpha7 nicotinic acetylcholine receptors) elicit the same neurophysiological events in schizophrenic patients and, subsequently, improve perception and cognitive functions will be determined when these drug candidates are available clinically.
目前的观察结果表明，神经元回路动力学功能障碍导致了精神分裂症患者大脑中异常的信息处理。据推测，精神分裂症患者听觉门控中断、P300诱发电位异常以及失配负波缺陷表明信息处理受损。最近，神经元同步性和振荡活动异常被认为是与精神分裂症相关的感知扭曲和认知功能障碍的潜在机制。这些新的观察结果可能揭示该疾病的病理生理学，并指出抗精神病药物治疗的潜在靶点。神经元回路动力学，如网络振荡和感觉门控过程，在系统发育上是保守的，这为设计转化生物标志物提供了绝佳机会。当这些候选药物可用于临床时，将确定影响网络振荡和感觉处理的临床前实验化合物（如α7烟碱型乙酰胆碱受体激动剂和调节剂）是否会在精神分裂症患者中引发相同的神经生理事件，并随后改善感知和认知功能。
