New genetic hypothesis of schizophrenia

• Published in: Medical hypotheses Vol. 52; no. 1; pp. 69 - 75
• Main Authors: Guidry, J., Kent, T.A.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.01.1999; Elsevier
• Subjects: Adult and adolescent clinical studies; Biological and medical sciences; Brain - abnormalities; Brain - growth & development; Diseases in Twins - genetics; Genes, Recessive; Genes, Tumor Suppressor; Humans; Medical sciences; Models, Biological; Models, Genetic; Mutation; Proto-Oncogenes; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - genetics; Twins, Monozygotic; Human; Pathogenesis; Schizophrenia; Genetics; Anomaly; Mutation; Onc gene; Structure; Protooncogene; Tumor suppressor gene
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1054/mehy.1997.0618

Lack of complete concordance for schizophrenia in monozygotic twins has been interpreted as indicative of non-genetic cofactors in transmission of the illness. We present an alternative hypothesis that can parsimoniously explain, using known genetic mechanisms, the heredity pattern, the phenotypic spectrum and the biological abnormalities found in schizophrenia. The inheritance of a single recessive mutated allele of a gene crucial in brain development if followed by a somatic mutation in the normal allele during critical periods of brain development could result in developmental abnormalities that are expressed behaviorally as schizophrenic illness. Acquisition of this somatic mutation is likely enhanced during periods of intense cell division; therefore, the window of opportunity would be restricted to key periods in neurodevelopment. The somatic mutation may not always occur, thus explaining the variability of expression seen in the clinical population. Because the single allele mutation is still transmissible, the equal incidence of schizophrenia in the offspring of monozygotic twins discordant for the disease could also be explained. This possibility has implications for the development of genetic models and the source of genetic material for studies isolating the gene(s) of schizophrenia.