Boggs Douglas L, Carlson Jon, Cortes-Briones Jose, Krystal John H, D'Souza D Cyril
Yale University School of Medicine, VACHS 151, 950 Campbell Avenue, West Haven CT 06516- 2770.
Curr Pharm Des. 2014;20(31):5077-92. doi: 10.2174/1381612819666131216121019.
Cognitive impairment is known to be a core deficit in schizophrenia. Existing treatments for schizophrenia have limited efficacy against cognitive impairment. The ubiquitous use of nicotine in this population is thought to reflect an attempt by patients to selfmedicate certain symptoms associated with the illness. Concurrently there is evidence that nicotinic receptors that have lower affinity for nicotine are more important in cognition. Therefore, a number of medications that target nicotinic acetylcholine receptors (nAChRs) have been tested or are in development. In this article we summarize the clinical evidence of nAChRs dysfunction in schizophrenia and review clinical studies testing either nicotine or nicotinic medications for the treatment of cognitive impairment in schizophrenia. Some evidence suggests beneficial effects of nAChRs based treatments for the attentional deficits associated with schizophrenia. Standardized cognitive test batteries have failed to capture consistent improvements from drugs acting at nAChRs. However, more proximal measures of brain function, such as ERPs relevant to information processing impairments in schizophrenia, have shown some benefit. Further work is necessary to conclude that nAChRs based treatments are of clinical utility in the treatment of cognitive deficits of schizophrenia.
认知障碍是精神分裂症的核心缺陷。现有的精神分裂症治疗方法对认知障碍的疗效有限。该人群中尼古丁的普遍使用被认为反映了患者试图自我治疗与该疾病相关的某些症状。同时,有证据表明对尼古丁亲和力较低的烟碱受体在认知中更为重要。因此,一些针对烟碱型乙酰胆碱受体(nAChRs)的药物已经过测试或正在研发中。在本文中,我们总结了精神分裂症中nAChRs功能障碍的临床证据,并回顾了测试尼古丁或烟碱类药物治疗精神分裂症认知障碍的临床研究。一些证据表明基于nAChRs的治疗对与精神分裂症相关的注意力缺陷有有益作用。标准化认知测试组合未能捕捉到作用于nAChRs的药物带来的持续改善。然而,更直接的脑功能测量方法,如与精神分裂症信息处理障碍相关的事件相关电位(ERP),已显示出一些益处。要得出基于nAChRs的治疗对精神分裂症认知缺陷具有临床实用性的结论,还需要进一步的研究。