Association between three functional polymorphisms of the dopamine D2 receptor gene and polydipsia in schizophrenia

The underlying pathophysiology of polydipsia in schizophrenia is poorly understood. However, several studies suggest there may be a genetic predisposition to polydipsia, including our previous study demonstrating familial concordance of polydipsia among first-degree relatives with schizophrenia. Antipsychotic medications may contribute to the development of polydipsia and studies show that dopamine D2 receptors are involved in drinking behaviour pathophysiology. Our hypothesis is that polymorphisms in the dopamine D2 receptor gene (DRD2) may confer susceptibility to polydipsia in schizophrenia. We tested for an association between polydipsia in schizophrenia and three functional polymorphisms of DRD2. The three polymorphisms, -141C Ins/Del, Ser311Cys, and TaqIA, were genotyped in patients with polydipsia (n = 64) and in those without polydipsia (n = 91). Of the three polymorphisms, TaqIA was significantly associated with polydipsia [genotype: chi2 = 6.59, df = 2, p = 0.037; allele: chi2 = 6.52, df = 1, p = 0.011, OR 1.81, 95% CI 1.15-2.86]. Haplotype analysis of the three markers found increased significance of the association (global, p = 0.00091). Although based on a relatively small portion of the sample, individual comparison of the common haplotypes showed that haplotype Ins-Cys-A1 was significantly less frequent in patients with polydipsia (p = 0.00082). The present data suggests polymorphisms in DRD2 may confer susceptibility to polydipsia in schizophrenia. To confirm our findings, further studies are warranted on larger samples using more extensive biological measures for diagnosing the polydipsia phenotype.