Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, Catanzaro, Italy.
Neuroimage. 2011 Mar 15;55(2):508-13. doi: 10.1016/j.neuroimage.2010.12.042. Epub 2010 Dec 22.
The dysbindin (dystrobrevin-binding protein 1) gene has been indicated as one of the most important schizophrenia susceptibility genes. Several genetic variations of this gene have been investigated by using an "intermediate phenotype" approach showing a particular detrimental effect on the prefrontal function in schizophrenic patients. However, the nature of dysbindin function within the brains of healthy individuals is poorly understood, in particular as concerns brain anatomy. We examine relationships between a previously implicated three marker C-A-T dysbindin haplotype and regional cortical thickness in a wide population genotyped for risk carriers (n=14) and non-risk carriers (n=93). Surface-based analysis of the cortical mantle showed that the dysbindin haplotype was associated with structural differences in the medial orbitofrontal cortex, where the risk carriers showed the highest cortical thickness values and the non-risk carriers the lowest. Our study extends previous evidence found on schizophrenic patients to the healthy population, demonstrating the influence of dysbindin risk variants on the neuronal architecture of a specific brain region relevant to the neuropathology of schizophrenia.
该 dysbindin（肌营养不良结合蛋白 1）基因已被指出是精神分裂症易感性最重要的基因之一。 该基因的几个遗传变异已通过使用“中间表型”方法进行了研究，该方法显示出对精神分裂症患者的前额叶功能有特殊的不利影响。 然而，在健康个体的大脑中，dysbindin 的功能性质尚不清楚，特别是在大脑解剖学方面。 我们检查了先前涉及的三个标记 C-A-T dysbindin 单倍型与广泛人群中风险携带者（n=14）和非风险携带者（n=93）的区域皮质厚度之间的关系。 皮质帽的基于表面的分析表明，dysbindin 单倍型与内侧眶额皮质的结构差异有关，其中风险携带者表现出最高的皮质厚度值，而非风险携带者则表现出最低的皮质厚度值。 我们的研究将先前在精神分裂症患者中发现的证据扩展到健康人群，证明了 dysbindin 风险变异对与精神分裂症神经病理学相关的特定脑区的神经元结构的影响。
