Department of Psychiatry, Virginia Institute of Psychiatric and Behavioral Genetics, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA, USA.
Department of Germanic Languages and Literatures, University of Toronto, Canada.
Schizophr Bull. 2022 Oct 19;48(Suppl 1):S8-S19. doi: 10.1093/schbul/sbac107.
In 1916, Ernst Rüdin published the first modern family study in the history of psychiatric genetics, the major goal of which was to test whether the pattern of risk in the siblings of dementia praecox (DP) probands followed Mendelian expectations. He utilized systematic ascertainment of probands and multisourced diagnostic assessments of probands and relatives, applying the narrow Kraepelinian concept of DP. In a novel step, he collaborated closely with a statistical geneticist-Wilhelm Weinberg-and applied his sibling, proband, and age correction methods. In his key sample-701 sibships when neither parent had DP-the morbid risk for DP in siblings was 4.48%, much lower than 25% expected for a recessive disorder. Risk for DP was increased by alcoholism or other mental disorders in parents. Other non-DP psychoses were common in both siblings and parents of DP probands. Rüdin discussed several alternative genetic models for DP including a 2-locus recessive, incomplete penetrance, and an oligogenic model. The high rates of other psychoses and psychopathic personalities in relatives might arise, he suggested, because these disorders shared genetic risks with DP. Rüdin established that DP, when carefully studied, ran in families, did not have a simple Mendelian genetic transmission pattern, and appeared likely to be genetically related to other non-DP psychotic disorders and perhaps some kinds of psychopathic personalities. This study, the most important in Rüdin's career, should be viewed in the context of his later extensive support of and collaboration with Nazi eugenic policies.
1916 年,Ernst Rüdin 发表了精神病遗传学史上第一份现代家族研究报告,主要目的是检验早发性痴呆(DP)先证者的兄弟姐妹的风险模式是否符合孟德尔的预期。他采用了系统性的先证者确定方法和多来源的先证者和亲属诊断评估,应用了狭义的克氏 DP 概念。在一个新颖的步骤中,他与一位统计遗传学家 Wilhelm Weinberg 密切合作,并应用了他的同胞、先证者和年龄校正方法。在他的关键样本——701 个同胞群体中,当父母双方都没有 DP 时——DP 同胞的病态风险为 4.48%,远低于隐性疾病的 25%预期。父母有酗酒或其他精神障碍会增加 DP 的风险。其他非 DP 精神病在 DP 先证者的兄弟姐妹和父母中都很常见。Rüdin 讨论了 DP 的几种替代遗传模型,包括双基因隐性、不完全外显率和寡基因模型。他认为,由于这些疾病与 DP 共享遗传风险,因此亲属中其他精神病和精神变态人格的发生率较高。Rüdin 确定 DP 在经过仔细研究后,在家庭中出现,没有简单的孟德尔遗传传递模式,并且很可能与其他非 DP 精神病和某些类型的精神变态人格有关。这项研究是 Rüdin 职业生涯中最重要的研究,应该结合他后来对纳粹优生政策的广泛支持和合作来进行观察。