Featherstone Robert E, Siegel Steven J
Translational Neuroscience Program, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Translational Neuroscience Program, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Int Rev Neurobiol. 2015;124:23-78. doi: 10.1016/bs.irn.2015.07.002. Epub 2015 Aug 21.
Schizophrenia is associated with by severe disruptions in thought, cognition, emotion, and behavior. Patients show a marked increase in rates of smoking and nicotine dependence relative to nonaffected individuals, a finding commonly ascribed to the potential ameliorative effects of nicotine on symptom severity and cognitive impairment. Indeed, many studies have demonstrated improvement in patients following the administration of nicotine. Such findings have led to an increased emphasis on the development of therapeutic agents to target the nicotinic system as well as increasing the impetus to understand the genetic basis for nicotinic dysfunction in schizophrenia. The goal of this review article is to provide a critical summary of evidence for the role of the nicotinic system in schizophrenia. The first part will review the role of nicotine in normalization of primary dysfunctions and endophenotypical changes found in schizophrenia. The second part will provide a summary of genetic evidence linking polymorphisms in nicotinic receptor genes to smoking and schizophrenia. The third part will summarize attempts to treat schizophrenia using agents specifically targeting nicotinic and nicotinic receptor subtypes. Although currently available antipsychotic treatments are generally able to manage some aspects of schizophrenia (e.g., positive symptoms) they fail to address several other critically effected aspects of the disease. As such, the search for novel mechanisms to treat this disease is necessary.
精神分裂症与思维、认知、情感和行为的严重紊乱有关。与未患病个体相比，患者的吸烟率和尼古丁依赖率显著增加，这一发现通常归因于尼古丁对症状严重程度和认知障碍的潜在改善作用。事实上，许多研究表明，给予尼古丁后患者的症状有所改善。这些发现使得人们更加重视开发针对烟碱系统的治疗药物，也增加了理解精神分裂症中烟碱功能障碍遗传基础的动力。这篇综述文章的目的是对烟碱系统在精神分裂症中的作用的证据进行批判性总结。第一部分将回顾尼古丁在精神分裂症中发现的原发性功能障碍和内表型变化正常化中的作用。第二部分将总结将烟碱受体基因多态性与吸烟和精神分裂症联系起来的遗传证据。第三部分将总结使用专门针对烟碱和烟碱受体亚型的药物治疗精神分裂症的尝试。尽管目前可用的抗精神病药物通常能够控制精神分裂症的某些方面（例如阳性症状），但它们无法解决该疾病其他几个受到严重影响的方面。因此，寻找治疗这种疾病的新机制是必要的。
