Association between different psychotic disorders and the DRD4 polymorphism, but no differences in the main ligand binding region of the DRD4 receptor protein compared to controls.

The dopamine D4 receptor gene (DRD4 gene) is one of the important candidate genes for schizophrenia and other psychoses. In humans, several alleles with variable repeat numbers of a 48-base-pair element within the third exon are known. The corresponding receptor proteins differ in their pharmacological properties. It might be possible that specific alleles or genotypes predispose for schizophrenia and other psychoses. The aim of the present study was to investigate and compare the frequency of the DRD4 alleles and genotypes in healthy controls and patients suffering from schizophrenia, schizoaffective or affective disorders. The DRD4 subtypes of 92 controls, 91 patients with schizophrenia, 90 patients with affective and 20 with schizoaffective disorders were identified by a combination of Southern blot technique and PCR. Statistical analysis revealed several significant differences between controls and patients, e.g. an increased frequency of the D4.7 allele among patients with schizophrenia, schizoaffective or unipolar affective disorder. The results indicate a possible role of the DRD4 gene polymorphism in the pathophysiology of psychotic diseases. When a part of the DRD4 gene sequence containing the codons for the most important amino acids for dopamine binding in 9 controls, 9 patients with schizophrenia and 10 with affective disorders were compared, no differences could be found.