The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia.
The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia.
复制标题
DOI：
10.1172/jci82636
复制
发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Lawrie SM
中科院分区：
文献类型：
--
作者：
Doyle OM;Bois C;Thomson P;Romaniuk L;Whitcher B;Williams SC;Turkheimer FE;Stefansson H;McIntosh AM;Mehta MA;Lawrie SM
背景精神分裂症1（DISC 1）基因位点的破坏最初是在一个苏格兰家系中发现的，该家系的精神疾病发病率高，与平衡t（1;11）（q42.1;q14.3）染色体易位有关。在这里，我们调查了这个家庭的成员携带t（1;11）（q42.1;q14.3）易位是否有一个共同的脑相关的表型，以及这种表型是否类似于精神分裂症（SCZ）中观察到的，使用多变量模式识别技术。方法.我们测量了健康对照（HC）（n = 24）、诊断为SCZ的患者（n = 24）、诊断为双相情感障碍（BP）的患者（n = 19）、以及DISC 1易位携带者（T+）或非携带者（T-）的原始苏格兰家族成员（n = 30）。开发了二元分类模型来评估各组之间的差异和相似性。结果基于皮质厚度，72%的T-组被分配到HC组，83%的T+组被分配到SCZ组，45%的BP组被分类为属于SCZ组，这表明该测量在预测脑相关表型方面具有高特异性。SCZ和T+个体之间共享的脑相关表型仅见于皮质厚度。最后，当直接比较T+和T-个体的皮质厚度的模式时，实现了73%的分类准确度。结论总之，这项研究的结果表明，DISC 1易位可能会增加精神疾病的风险，在这个家系中，通过影响神经结构表型，如皮质厚度。经费这项工作得到了苏格兰国家卫生服务研究所、苏格兰转化医学研究合作组织、创新药物倡议（IMI）、工程和物理科学研究理事会（EPSRC）、威康信托基金会、国家卫生研究所（NIHR）和辉瑞公司的支持。
BACKGROUND. The disrupted in schizophrenia 1 (DISC1) gene locus was originally identified in a Scottish pedigree with a high incidence of psychiatric disorders that is associated with a balanced t(1;11)(q42.1;q14.3) chromosomal translocation. Here, we investigated whether members of this family carrying the t(1;11)(q42.1;q14.3) translocation have a common brain-related phenotype and whether this phenotype is similar to that observed in schizophrenia (SCZ), using multivariate pattern recognition techniques. METHODS. We measured cortical thickness, cortical surface area, subcortical volumes, and regional cerebral blood flow (rCBF) in healthy controls (HC) (n = 24), patients diagnosed with SCZ (n = 24), patients diagnosed with bipolar disorder (BP) (n = 19), and members of the original Scottish family (n = 30) who were either carriers (T+) or noncarriers (T–) of the DISC1 translocation. Binary classification models were developed to assess the differences and similarities across groups. RESULTS. Based on cortical thickness, 72% of the T– group were assigned to the HC group, 83% of the T+ group were assigned to the SCZ group, and 45% of the BP group were classified as belonging to the SCZ group, suggesting high specificity of this measurement in predicting brain-related phenotypes. Shared brain-related phenotypes between SCZ and T+ individuals were found for cortical thickness only. Finally, a classification accuracy of 73% was achieved when directly comparing the pattern of cortical thickness of T+ and T– individuals. CONCLUSION. Together, the results of this study suggest that the DISC1 translocation may increase the risk of psychiatric disorders in this pedigree by affecting neurostructural phenotypes such as cortical thickness. FUNDING. This work was supported by the National Health Service Research Scotland, the Scottish Translational Medicine Research Collaboration, the Innovative Medicines Initiative (IMI), the Engineering and Physical Sciences Research Council (EPSRC), The Wellcome Trust, the National Institute of Health Research (NIHR), and Pfizer.