Shihabuddin L, Silverman J M, Buchsbaum M S, Seiver L J, Luu C, Germans M K, Metzger M, Mohs R C, Smith C J, Spiegel-Cohen J, Davis K L
Department of Psychiatry Service, Bronx VA Medical Center, NY 10468, USA.
Mol Psychiatry. 1996 Jul;1(3):215-22.
We previously obtained evidence indicating a genetic linkage marker for schizophrenia and related disorders (two-point lod score = 3.72, P = 0.01) on the short arm of chromosome 5(5p14.1-13.1) in one large pedigree. Automated computer algorithms were used to edge the brain and measure the volume of the ventricles, regional sulcal atrophy, and skull size and shape in the original nuclear family members. Of the 11 subjects who underwent computed tomography, six (three schizophrenic, two with schizotypal personality disorder, and one unaffected) carried the marker allele that co-segregated with schizophrenia-related disorders, while five (all unaffected) did not. The family members with the marker allele linked to schizophrenia-related disorders (n = 6) had significantly (P < 0.05) larger ventricle-brain ratios (VBRs) and more fronto-parietal atrophy (controlling for age) than the family members lacking the schizophrenia-related marker allele (n = 5). The three individuals with the largest VBRs all carried the marker, although they received diagnoses of no schizophrenia-related disorder, schizotypal personality disorder, and schizophrenia. Regional cortical values indicative of cerebrospinal fluid content were higher in the frontal and parietal regions of family members carrying the marker. The hypothesis that genetic linkage is associated with structural brain pathology is difficult to test because of all the potential compounding factors. Our findings suggest the possibility that, in this family, relatively enlarged VBR and fronto-parietal atrophy, as determined by computed tomograph, may be associated with a schizophrenia-related gene and present susceptibility to schizophrenia-related disorders. In addition to a replication of these findings in other similarly linked families yet to be identified, further studies using higher resolution structural and functional neuroimaging techniques will be required.
我们之前获得的证据表明，在一个大型家系中，5号染色体短臂（5p14.1 - 13.1）上存在精神分裂症及相关障碍的遗传连锁标记（两点连锁对数得分 = 3.72，P = 0.01）。使用自动化计算机算法勾勒大脑边缘，并测量原始核心家庭成员的脑室体积、局部脑沟萎缩以及颅骨大小和形状。在接受计算机断层扫描的11名受试者中，6名（3名精神分裂症患者、2名分裂型人格障碍患者和1名未患病者）携带与精神分裂症相关障碍共分离的标记等位基因，而5名（均未患病）则没有。与缺乏精神分裂症相关标记等位基因的家庭成员（n = 5）相比，携带与精神分裂症相关障碍连锁的标记等位基因的家庭成员（n = 6）具有显著更高（P < 0.05）的脑室 - 脑比率（VBR）和更多的额顶叶萎缩（校正年龄后）。VBR最大的三名个体均携带该标记，尽管他们被诊断为无精神分裂症相关障碍、分裂型人格障碍和精神分裂症。携带该标记的家庭成员额叶和顶叶区域中指示脑脊液含量的区域皮质值更高。由于所有潜在的混杂因素，很难检验遗传连锁与脑结构病理相关这一假设。我们的研究结果表明，在这个家系中，计算机断层扫描所确定的相对增大的VBR和额顶叶萎缩可能与一个精神分裂症相关基因有关，并呈现出对精神分裂症相关障碍的易感性。除了在其他尚未确定的类似连锁家系中重复这些发现外，还需要使用更高分辨率的结构和功能神经成像技术进行进一步研究。
