Association study of dopamine receptor genes polymorphism with cognitive functions in bipolar I disorder patients.

OBJECTIVE: To determine the correlation among the polymorphisms of dopamine receptor genes, cognitive function of Bipolar disorder (BD) patients, and BD.

METHODS: Twenty-three Single Nucleotide Polymorphisms (SNPs) of dopamine receptor genes were genotyped using Illumina GoldenGate genotyping assay in 375 patients with bipolar I disorder (BD-I) (patients group) and 475 healthy controls (control group). Cognitive function tests were performed in 158 patients who were clinically stable and 307 healthy controls who were matched with the patients in age, sex, and education.

RESULTS: The allele frequencies of rs3758653 in the promoter region of the DRD4 gene were significantly different between patients group and control group (χ(2)=9.386, Corrected P=0.046). This significant difference was also observed between BD-I patients with psychotic symptoms and healthy controls (χ(2)=9.27, Corrected P=0.049). Patients with BD-I performed significantly worse than healthy controls in all cognitive domains (p<0.01) except TMTA errors and illegal time. Significant interactions between polymorphisms of rs5326 in DRD1 gene and phenotype (affected or unaffected with BD-I) were found in non-perseverative errors (β=3.20 and Corrected P=0.0034) on the Wisconsin Card Sorting Test (WCST). The allele of this SNP denoted the positive effect on the WCST non-perseverative errors in BD-I patients group (β=2.80 and Corrected P=0.017). The genotypic association analyses also supported the findings (F=4.24 and P=0.007), but this effect was not found in controls.

LIMITATIONS: The sample size was relatively small and the SNP coverage was limited, making it very important to be cautious when drawing a conclusion.

CONCLUSIONS: DRD4 gene may play an important role in psychotic symptomatology rather than in unique diagnosis, BD, for example. A genetic association exists between DRD1 gene and impaired cognition in BD.