Rüdin's 1916 Monograph: On the Inheritance and Primary Origin of Dementia Praecox

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.