DRD4 exon 3 variants associated with delusional symptomatology in major psychoses: a study on 2,011 affected subjects.

We previously reported an association of DRD4 exon3 long allele variants with delusional symptomatology independently from diagnoses. The aim of this investigation was to study DRD4 in major psychoses and to test the association in a larger sample. We studied 2,011 inpatients affected by bipolar disorder (n = 811), major depressive disorder (n = 635), schizophrenia (n = 419), delusional disorder (n = 104), psychotic disorder not otherwise specified (n = 42), and 601 healthy controls. A subsample of 1,264 patients were evaluated using the OPCRIT checklist and differences of symptomatology factor scores among genetic variants were assessed using one-way analysis of variance (ANOVA). DRD4 allele and genotype frequencies in bipolars, schizophrenics, delusionals, and psychotic NOS were not significantly different from controls; major depressives showed a trend toward an excess of DRD4*Short and DRD4*Short/Short variants versus controls. The ANOVA on factor scores in the whole subsample of 1,264 subjects showed a significant difference on delusion factor in allele analysis (P = 0.007), and in genotype one (P = 0.018), with DRD4*Long containing variants associated with severe symptomatology. The analysis in the replication subjects only (n = 803) showed a trend in the same direction, though not reaching the significance level. This analysis in an enlarged sample suggests that DRD4*Long alleles exert a small but significant influence on the delusional symptomatology in subjects affected by major psychoses.