Steel R M, Whalley H C, Miller P, Best J J K, Johnstone E C, Lawrie S M
University of Edinburgh, Department of Psychiatry, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK.
J Neurol Neurosurg Psychiatry. 2002 Apr;72(4):455-8. doi: 10.1136/jnnp.72.4.455.
Schizophrenia is a highly heritable disorder associated with structural brain abnormalities. The aim of this study was to establish if the gene(s) for schizophrenia are associated with specific abnormalities of brain structure.
Six sibships from multiple affected families were recruited. Each sibship consisted of one patient with schizophrenia, one "obligate carrier" without the disorder but with an affected child, and one "non-affected non-carrier". Such sibships are very rare, but present a powerful opportunity to separate the associations of genotype and phenotype. Obligates presumably have the gene(s) but not the disorder, affected siblings have both, whereas non-affected non-carrier siblings have neither.
Brain MRI was conducted with a semiautomated region of interest analysis. The risk of false positive findings was reduced by collapsing brain regions and sides into five regions and comparing groups by repeated measures analysis of variance.
In terms of whole brain volumes and volumes of cortical structures, obligates resembled their non-affected non-carrier siblings, both groups having significantly greater volumes than their schizophrenic siblings (p=0.01 and p=0.04). Obligates also had significantly smaller ventricles than their schizophrenic siblings (p=0.03). However, with respect to the amygdalohippocampal complex, the obligates' brains resembled those of their schizophrenic siblings, both groups showing a significant reduction in volume when compared with their non-affected non-carrier siblings (p=0.001).
In the families studied, reductions in volumes of cortical structures and reductions in whole brain volume seem to be associated with the phenotype of schizophrenia. By contrast, reduced volume of the amygdalohippocampal complex seems to be associated with genetic risk for the disorder even in the absence of disease.
精神分裂症是一种与大脑结构异常相关的高度遗传性疾病。本研究的目的是确定精神分裂症相关基因是否与特定的脑结构异常有关。
招募了来自多个患病家庭的6个同胞组。每个同胞组由一名精神分裂症患者、一名未患该病但有患病子女的“必然携带者”和一名“未患病非携带者”组成。这种同胞组非常罕见，但提供了一个区分基因型和表型关联的有力机会。必然携带者大概携带相关基因但未患该病，患病同胞两者皆有，而未患病非携带者同胞两者皆无。
采用半自动感兴趣区域分析进行脑部磁共振成像（MRI）。通过将脑区和脑侧合并为五个区域，并采用重复测量方差分析比较各组，降低了假阳性结果的风险。
就全脑体积和皮质结构体积而言，必然携带者与其未患病非携带者同胞相似，两组的体积均显著大于其精神分裂症同胞（p = 0.01和p = 0.04）。必然携带者的脑室也明显小于其精神分裂症同胞（p = 0.03）。然而，就杏仁核 - 海马复合体而言，必然携带者的大脑与其精神分裂症同胞的大脑相似，与未患病非携带者同胞相比，两组的体积均显著减小（p = 0.001）。
在所研究的家庭中，皮质结构体积减小和全脑体积减小似乎与精神分裂症的表型有关。相比之下，即使在没有疾病的情况下，杏仁核 - 海马复合体体积减小似乎也与该疾病的遗传风险有关。
