Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia
Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia
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DOI：
10.1038/mp.2008.28
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发表时间：
2009-11-01
影响因子：
11
通讯作者：
Dean, B.
中科院分区：
文献类型：
--
作者：
Scarr, E.;Cowie, T. F.;Dean, B.
精神分裂症被广泛认为是一种综合征，由可能具有不同病理的不确定数量的疾病组成。虽然研究一个综合征使识别潜在的病理学更加困难;神经影像学，神经精神药理学和死后大脑研究都涉及毒蕈碱乙酰胆碱受体（CHRM）在疾病的病理学。我们已经确定，CHRM 1是选择性地减少在背外侧前额叶皮层的精神分裂症患者。为了扩展这一发现，我们想确定皮质CHRM减少是否可能（1）定义精神分裂症的一个亚组和/或（2）与CHRM 1基因型有关。我们评估了80名精神分裂症患者和74名年龄性别匹配的对照组的皮质[H-3]哌仑西平结合和CHRM 1测序。核密度估计表明，[H-3]哌仑西平结合BA 9分为精神分裂症，但不控制，队列成两个不同的人群。其中一个精神分裂症队列（占所有精神分裂症受试者的26%）与对照组相比，平均皮质[H-3]哌仑西平结合减少了74%。我们认为，这些人构成了“毒蕈碱受体缺陷型精神分裂症”（MRDS）。MRDS不能通过CHRM 1序列、性别、年龄、自杀、疾病持续时间或任何特定药物治疗与其他精神分裂症受试者分开。能够使用中心生物学参数定义精神分裂症中的亚组是理解至少一种形式的疾病的生物化学的关键一步，并且可能代表可用于神经成像的生物标志物。分子精神病学（2009）14，1017-1023; doi：10.1038/mp.2008.28;在线发表2008年3月4日
Schizophrenia is widely acknowledged as being a syndrome, consisting of an undefined number of diseases probably with differing pathologies. Although studying a syndrome makes the identification of an underlying pathology more difficult; neuroimaging, neuropsychopharmacological and post-mortem brain studies all implicate muscarinic acetylcholine receptors (CHRM) in the pathology of the disorder. We have established that the CHRM1 is selectively decreased in the dorsolateral prefrontal cortex of subjects with schizophrenia. To expand this finding, we wanted to ascertain whether decreased cortical CHRMs might (1) define a subgroup of schizophrenia and/or (2) be related to CHRM1 genotype. We assessed cortical [H-3] pirenzepine binding and sequenced the CHRM1 in 80 subjects with schizophrenia and 74 age sex-matched control subjects. Kernel density estimation showed that [H-3] pirenzepine binding in BA9 divided the schizophrenia, but not control, cohort into two distinct populations. One of the schizophrenia cohorts, comprising 26% of all subjects with the disorder, had a 74% reduction in mean cortical [H-3] pirenzepine binding compared to controls. We suggest that these individuals make up 'muscarinic receptor-deficit schizophrenia' (MRDS). The MRDS could not be separated from other subjects with schizophrenia by CHRM1 sequence, gender, age, suicide, duration of illness or any particular drug treatment. Being able to define a subgroup within schizophrenia using a central biological parameter is a pivotal step towards understanding the biochemistry underlying at least one form of the disorder and may represent a biomarker that can be used in neuroimaging. Molecular Psychiatry (2009) 14, 1017-1023; doi:10.1038/mp.2008.28; published online 4 March 2008