ABSTRACT Schizophrenia is a common mental illness with a high prevalence of smoking. More than 80% of schizophrenics smoke compared to 25% of the general population. Both schizophrenia and tobacco use have strong genetic components, which may overlap. It has been suggested that smoking in schizophrenia may be a form of self-medication in an attempt to treat an underlying biological pathology. Smoking normalizes auditory evoked potential and eye tracking deficits in schizophrenia, as well as improving cognitive function. Nicotine acts through a family of nicotinic receptors with either high or low affinity for nicotine. The loci for several of these receptors have been genetically linked to both smoking and to schizophrenia. Smoking changes gene expression for more than 200 genes in human hippocampus, and differentially normalizes aberrant gene expression in schizophrenia. The α7* nicotinic receptor, linked to schizophrenia and smoking, has been implicated in sensory processing deficits and is important for cognition and protection from neurotoxicity. Nicotine, however, has multiple health risks and desensitizes the receptor. A Phase I trial of DMXB-A, an α7* agonist, shows improvement in both P50 gating and in cognition, suggesting that further development of nicotinic cholinergic drugs is a promising direction in schizophrenia research.

中文翻译：

---

吸烟与精神分裂症的遗传学


摘要：精神分裂症是一种常见的精神疾病，吸烟患病率很高。超过 80% 的精神分裂症患者吸烟，而普通人群的这一比例为 25%。精神分裂症和吸烟都有很强的遗传成分，而且可能有重叠。有人认为，精神分裂症患者吸烟可能是一种自我治疗的形式，试图治疗潜在的生物病理学。吸烟可以使精神分裂症的听觉诱发电位和眼动追踪缺陷正常化，并改善认知功能。尼古丁通过对尼古丁具有高或低亲和力的烟碱受体家族起作用。其中一些受体的位点与吸烟和精神分裂症有遗传相关。吸烟会改变人类海马体中 200 多个基因的基因表达，并使精神分裂症中的异常基因表达差异正常化。 α7* 烟碱受体与精神分裂症和吸烟有关，与感觉处理缺陷有关，对于认知和防止神经毒性很重要。然而，尼古丁具有多种健康风险，并使受体变得不敏感。 DMXB-A（一种 α7* 激动剂）的 I 期试验显示 P50 门控和认知均有所改善，表明烟碱胆碱能药物的进一步开发是精神分裂症研究的一个有前途的方向。