| 1 | 摩尔。Psychiatry 2012 Sep 17: 906-17 |
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| PMID | 21747397 |
| Title | Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe. |
| Abstract | Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture ofschizophrenia(SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through the recruitment of very large samples of patients and controls (that is tens of thousands), or large, potentially more homogeneous samples that have been recruited from confined geographical areas using identical diagnostic criteria. Applying the latter strategy, we performed a genome-wide association study (GWAS) of 1169 clinically well characterized and ethnically homogeneous SCZ patients from a confined area of Western Europe (464 from Germany, 705 from The Netherlands) and 3714 ethnically matched controls (1272 and 2442, respectively). In a subsequent follow-up study of our top GWAS results, we included an additional 2569 SCZ patients and 4088 controls (from Germany, The Netherlands and Denmark). Genetic variation in a region on chromosome 11 that contains the candidate genes AMBRA1, DGKZ,CHRM4在组合样品中，MDK与SCZ显着相关（n = 11？540； p = 3.89�10（-9），优势比（OR）= 1.25）。在23？206欧洲血统的独立样本中复制了这一发现（p = 0.0029，OR = 1.11）。在随后的成像遗传学研究中，风险等位基因的健康载体在认知控制任务期间表现出扣带回皮层的激活改变。感兴趣的领域是情绪调节和认知之间的关键接口，在SCZ和双相情感障碍中在结构和功能上异常。 |
| SCZ关键字 | schizophrenia |
| 2 | Schizophr. Res. 2013 May 146: 279-84 |
| PMID | 23490763 |
| Title | 胆碱能毒蕈碱M4受体基因多态性：精神分裂症的潜在危险因素和药物基因组标记。 |
| Abstract | 虽然schizophreniais a widespread disorder of unknown aetiology, we have previously shown that muscarinic M4 receptor (CHRM4) expression is decreased in the hippocampus and caudate-putamen from subjects with the disorder, implicating the receptor in its pathophysiology. These findings led us to determine whether variation in theCHRM4gene sequence was associated with an altered risk ofschizophrenia通过测序CHRM4来自76人患有这种疾病的人的大脑，没有精神病史的74人。另外，因为CHRM4is a potential target for antipsychotic drug development, we investigated whether variations inCHRM4sequence were associated with final recorded doses of, and life-time exposure to, antipsychotic drugs. Gene sequencing identified two single nucleotide polymorphisms (SNPs; rs2067482 and rs72910092) in theCHRM4基因。对于RS2067482，我们的数据表明，基因型（1341C/C; P = 0.05）和等位基因（C; P = 0.03）都与增加的风险增加有关schizophrenia. In addition, there was a strong trend (p = 0.08) towards an association betweenCHRM4sequence and increased lifetime exposure to antipsychotic drugs. Furthermore, there was a trend for people with the C allele to be prescribed benzodiazepines more frequently (p = 0.06) than those with the T allele. These data, albeit on small cohorts, are consistent with genetic variance at rs2067482 contributing to an altered risk of developingschizophreniawhich requires more forceful pharmacotherapy to achieve a clinical response. |
| SCZ关键字 | schizophrenia |
| 3 | Curr。摩尔。医学2015 -1 15：253-64 |
| PMID | 25817858 |
| Title | 毒蕈碱受体可能参与精神疾病：精神分裂症和情绪障碍的重点。 |
| Abstract | A considerable body of data supports a role for the central cholinergic system in the aetiologies ofschizophreniaand mood disorders. There have been breakthroughs in gaining structural data on muscarinic receptors (CHRMs), understanding their role in CNS functioning and in synthesising drugs that can specifically target each of the 5 CHRMs. This means it is opportune to consider the role of specific CHRMs in the pathophysiologies ofschizophreniaand mood disorders. This review will focus on data suggesting changes in levels of CHRM1 andCHRM4implicate these receptors in the pathophysiology ofschizophreniawhereas data suggest a role for CHRM2 in mood disorders. There will be a selected reference to recent developments in understanding the roles of CHRM1, 2 and 4 in CNS function and how these predict mechanisms by which these receptors could induce the symptoms prevalent inschizophreniaand mood disorders. Finally, there will be comments on the potential advantages and problems in targeting CHRM1 andCHRM4to treat the symptoms ofschizophreniaand CHRM2 to treat the symptom of depression. |
| SCZ关键字 | schizophrenia |
| 4 | Curr。Pharm。des。2016 -1 22：2124-33 |
| PMID | 26818859 |
| Title | The Cholinergic System: An Emerging Drug Target for Schizophrenia. |
| Abstract | 认知缺陷是社会上最衰弱，最有效治疗的症状之一schizophrenia. The cholinergic system is a promising target for the design of novel drugs that can more effectively treat these symptoms. We review the literature supporting the dysfunction of the cholinergic system inschizophrenia, discuss the preclinical and clinical data showing that modulating the cholinergic system could improve the symptoms ofschizophreniaand review the main pharmacological strategies being investigated to treat cholinergic dysfunction inschizophrenia. 验尸后和神经影像学研究表明，皮质以及皮层下区域（例如海马和纹状体）在患有皮质和皮质下区域的胆碱能受体信号传导广泛减少。schizophrenia. Potential cholinergic drug targets are being pursued to increase receptor function. These include inhibiting the activity of the enzyme acetylcholinesterase to increase synaptic acetylcholine levels, and increasing the nicotinic receptor and muscarinic receptor activity with agonists or positive allosteric modulators. Amongst the most promising drug targets for treatingschizophreniaare the ?7 nicotinic receptor and the CHRM1 andCHRM4muscarinic receptors. The recent development of allosteric modulators that selectively target these receptors offers the potential to more effectively treat the symptoms ofschizophrenia. |
| SCZ关键字 | schizophrenia |