Kendler K S, Myers J M, O'Neill F A, Martin R, Murphy B, MacLean C J, Walsh D, Straub R E
Department of Psychiatry, Medical College of Virginia of Virginia Commonwealth University, Richmond, VA 23298-0710, USA.
Am J Psychiatry. 2000 Mar;157(3):402-8. doi: 10.1176/appi.ajp.157.3.402.
Schizophrenia is clinically heterogeneous. Recent linkage studies suggest that multiple genes are important in the etiology of schizophrenia. The authors examined the hypothesis of whether the clinical variability in schizophrenia is due to genetic heterogeneity.
Using data from the Irish Study of High-Density Schizophrenia Families (N=265 pedigrees; N=1,408 individuals), the authors attempted to predict, from major symptoms and signs of psychosis, evidence for linkage within families for schizophrenia-related disorders to chromosomal regions 5q21-5q31, 6p24-6p22, 8p22-8p21, and 10p15-10p11.
No substantial evidence was found for associations between clinical features of schizophrenia and linkage to chromosomes 5q, 6p, or 10p. However, affected individuals from families with evidence for linkage to 8p had significantly more affective deterioration, poorer outcome, more thought disorder, and fewer depressive symptoms than affected individuals from the other families in the study.
These results raise the possibility that the putative susceptibility gene for schizophrenia localized in the 8p22-8p21 region may predispose individuals to the core dementia-praecox syndrome described by Kraepelin more than 100 years ago.
精神分裂症在临床上具有异质性。近期的连锁研究表明，多个基因在精神分裂症的病因学中起重要作用。作者检验了精神分裂症临床变异性是否归因于基因异质性这一假说。
利用来自爱尔兰高密度精神分裂症家族研究的数据（N = 265个家系；N = 1408人），作者试图根据精神病的主要症状和体征，预测精神分裂症相关障碍在家族内与5q21 - 5q31、6p24 - 6p22、8p22 - 8p21和10p15 - 10p11染色体区域的连锁证据。
未发现精神分裂症临床特征与5q、6p或10p染色体连锁之间存在实质性关联证据。然而，与研究中的其他家族相比，来自与8p连锁的家族的患病个体有更明显的情感恶化、预后更差、思维障碍更多且抑郁症状更少。
这些结果增加了一种可能性，即定位于8p22 - 8p21区域的假定精神分裂症易感基因可能使个体更易患100多年前克雷佩林所描述的核心早发性痴呆综合征。
