[Molecular genetic approach to schizophrenia: direct analysis of 5-HT receptor genes]

The influence of genetic factors in schizophrenia has been demonstrated by family, twin and adoption studies. The first-degree relatives of patients with schizophrenia have a risk of schizophrenia that is about 10 times greater than that of the general population. Concordance rate for schizophrenia is higher in monozygotic twins that in dizygotic twins. Biological relatives of individuals with schizophrenia have an increased risk of schizophrenia, although adoptive relatives have no increased risk. Many findings suggest the important role of serotonin (5-HT) in the pathophysiology of schizophrenia. Our direct analysis of 5-HT receptor genes in schizophrenia by single stranded conformational polymorphism revealed amino acid substitution in the 5-HT2A and 2C receptor genes. There is no association between the amino acid substitution in the 5-HT2A and 2C receptor genes and the antipsychotic response to clozapine, although both of the substitutions showed the functional influence of these receptors. So far linkage, affected sib pair and association studies have not been able to identify a susceptibility gene for schizophrenia. The molecular genetic approach to schizophrenia has been complicated by genetic heterogeneity, phenotypic heterogeneity and the small family size of this disorder.