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A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Luxenburger's 1939 Essay on "Schizophrenia and its Hereditary Circle"
Kenneth S Kendler1, Astrid Klee2
1Virginia Institute of Psychiatric and Behavioral Genetics, and Department of Psychiatry, Medical College of Virginia/Virginia Commonwealth University, Richmond, Virginia, USA.
Abstract:
In 1939, Hans Luxenburger published a detailed overview of the current status of schizophrenia genetics research, reaching six major conclusions. First, schizophrenia is clearly a hereditary disease. Second, however, schizophrenia is not the hereditary trait itself but rather the consequences of a slowly developing biological progress, the nature of which remains entirely unknown. Third, the full manifestation of the disorder requires certain environmental influences that must come into play. In around 30% of cases, the environment can inhibit hereditary factors so that the predisposition does not manifest in schizophrenia. Fourth, the mode of inheritance of schizophrenia remains unknown, although recessivity is more likely than dominance and monomerism is more likely than polymerism. Fifth, current evidence suggests that schizophrenia is likely etiologically homogenous. Sixth, schizophrenia is part of a hereditary circle that includes "normal" variants of the human personality (schizothymia), a pathological version of this dimension (schizoidia), and other schizophrenia-like delusional syndromes. Luxenburger is skeptical of efforts to clarify further Mendelian transmission models in the absence of pathophysiological markers because schizophrenia cannot serve as a typical phenotype for genetic analysis. By contrast, he strongly supports empirical work on hereditary prognosis, which does not depend on assumptions about any particular phenotype-genotype relationship.
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