Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Department of Psychiatry, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA, USA.
Schizophr Bull. 2022 Oct 19;48(Suppl 1):S45-S55. doi: 10.1093/schbul/sbac111.
In his 1933 article, Bruno Schulz reported a follow-up and reanalysis of the schizophrenic probands and their relatives first studied by Rüdin 20 years earlier that sought to clarify whether schizophrenia was a valid "unit-character" for Mendelian genetic analysis. He proposed a range of subgroupings of probands, particularly traditional subtyping, presence or absence of identifiable causal influences, and outcome. He then compared those subgroupings in several ways, most commonly by the risk for schizophrenia in their siblings and by the level of resemblance among proband-sibling affected pairs. Of his many findings, those of greatest interest included (1) probands with possible and probable physical causes, particularly those with head trauma, had substantially lower risk of illness in siblings, (2) probands with a hebephrenic subtype had a striking elevation of risk for schizophrenia in siblings, (3) probands with psychological causes had higher rates of good outcome, (4) proband-sibling pairs resembled one another for the classical schizophrenic subtypes, and (5) an absence of any cases of schizophrenia in siblings of a small group of schizophrenic probands with birth complications, convulsions, and skull deformities. Schulz used this sample in a fundamentally different way than Rüdin. Rather than seeking for Mendelian transmission patterns, Schulz used family data to evaluate hypothesis about clinical/etiological heterogeneity, thereby presaging many subsequent family studies of psychiatric disorders. While Schulz did not claim to have proved the etiologic heterogeneity of schizophrenia, he raised important questions, still unanswered, about whether schizophrenia is a legitimate "unit-character" appropriate for genetic analysis.
在他 1933 年的文章中,布鲁诺·舒尔茨(Bruno Schulz)报告了对 20 年前鲁丁(Rüdin)首次研究的精神分裂症先证者及其亲属的随访和重新分析,旨在阐明精神分裂症是否是孟德尔遗传分析的有效“单位特征”。他提出了一系列先证者的亚组分类,特别是传统的亚型分类、是否存在可识别的因果影响以及结果。然后,他以多种方式比较了这些亚组,最常见的是通过兄弟姐妹的精神分裂症风险以及先证者-兄弟姐妹受影响对的相似程度。在他的许多发现中,最引人关注的包括:(1)有潜在或可能的身体原因的先证者,特别是头部受伤的先证者,其兄弟姐妹的患病风险大大降低;(2)具有青春型亚型的先证者,其兄弟姐妹的精神分裂症风险显著升高;(3)有心理原因的先证者有更高的良好结局率;(4)先证者-兄弟姐妹对在经典精神分裂症亚型上彼此相似;(5)在一小部分有出生并发症、惊厥和颅骨畸形的精神分裂症先证者的兄弟姐妹中,没有任何精神分裂症病例。舒尔茨以与鲁丁根本不同的方式使用了这个样本。他没有像鲁丁那样寻求孟德尔遗传模式,而是利用家族数据来评估关于临床/病因异质性的假设,从而预示了许多随后对精神障碍的家族研究。虽然舒尔茨并没有声称已经证明精神分裂症的病因异质性,但他提出了一些重要的问题,这些问题仍然没有得到解答,即精神分裂症是否是一个合适的遗传分析的“单位特征”。