Genetic factors

Schizophrenia is a psychotic disorder of complex inheritance. The risk of developing the disorder is 1% in the general population but rises to 50% for monozygotic twins of an affected proband and approximately 10% for a sibling of a parent.

Schizophrenia does not fit into a pattern of inheritance seen for a single dominant gene but does fit the pattern of oligogenic inheritance. One of the main problems that arises in trying to summarize the evidence in favour of a specific genetic loci has been the difficulty in replicating the evidence. Thus conflicting results for the link between loci on chromosomes 5, 8, 11 and 22 and schizophrenia are apparent. Perhaps the most robust finding, and even this has not been universally replicated, has been the identification of a gene on the short arm of chromosome 6 which involves several markers in the region 6p21-24.

Because of the hypothesized abnormality in the dopaminergic system and schizophrenia, genes for the five types of dopamine receptor genes were the first to be studied in detail. Neither the D1 or D5 receptor gene would appear to be linked or to have polymorphisms associated with the disorder. Despite the apparent link between the D2 receptor and the action of antipsychotic drugs, no evidence of a genetic link has been found. Similarly, the observation that the D4 receptor was located primarily in the mesocortical limbic region of the brain, and for which many atypical antipsychotics had an affinity, led to a study of the polymorphic forms of the gene. Despite the initial success that showed a link between the D4 receptor and schizophrenia, the findings could not be replicated. No link with D3 or 5-HT2 receptor genes has been observed.

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