[Genetic factors in the onset of schizophrenia]

Abstract

The importance of inheritance in the development of schizophrenia was recorded in classic papers by Kraepelin and Bleuler. These observations have been confirmed by the contemporary research. In this paper, we summarize the results of genetic-epidemiological studies that include family, twin and adoption studies, as well as the results of segregation analysis and molecular-genetic research. Family studies indicate increased morbidity risk in the relatives of patients with schizophrenia, that augments with the degree of relation. Twin studies also suggest the importance of genetic factors demonstrating higher rates of concordance for the disorder in monozygotic (MZ) than in dizygotic (DZ) twins and consistent MZ/DZ ratios across the studies. Adoption studies provide further evidence for genetic vulnerability, showing an association between biological relatives separated at birth. The concept of "schizophrenia spectrum" is based on the observation of the familial aggregation of several hierarchically defined disorders in relatives of schizophrenic probands. Schizophrenia, schizoaffective disorder, schizotypal and paranoid personality disorder, other nonaffective psychoses and psychotic affective disease, according to this concept, represent manifestations of varying severity, of the same underlying vulnerability, which is transmitted within families. The results of segregation analyses support rather polygenic than monogenic inheritance, if schizophrenia is genetically homogeneous. However, the possibility of genetic heterogeneity augments the interest for searching for vulnerability genes with linkage. The results of linkage studies, indicating association between schizophrenia and markers on chromosomes 5, 6, 8 and 22, have not yet been replicated on independent samples of probands. Recent findings indicate that schizophrenia may be caused by unstable DNA (the expansion of trinucleotide repeated sequences at the disease locus). This could explain the departure from Mendelian inheritance, highly variable phenotype and wide ranging age of onset in schizophrenia. Further research in this field could not only clarify the mode of the transmission of the liability for schizophrenia and the relationship of genetic and environmental factors in the development of the disorder, but also determine which characteristics, behavior and physiological variables schizophrenia genes code for. This would, in addition, contribute to our understanding of the biological basis of schizophrenia.