Genetic variants of the BDNF and DRD3 genes in bipolar disorder comorbid with anxiety disorder

Abstract

Background: The high comorbidity rate between bipolar disorder (BP) and anxiety disorder (AD) has been studied in depth. This comorbidity is not as high in Han Chinese in Taiwan. Therefore, we explored the genetic effects BP comorbid with AD.

Methods: We recruited 1316 participants: 286 with BP-I, 681 with BP-II, and 349 healthy Controls. Genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.

Results: The DRD3 Ser9Gly polymorphism was associated with BP-II comorbid with AD (BPII(+AD)), and the BDNF Val66Met polymorphism was associated with BP-I comorbid with AD (BPI(+AD)). An interaction between the Val/Val genotype of the BDNF Val66Met and Gly/Gly polymorphism of the DRD3 Ser9Gly was found in BPII(+AD), but not in BP-II not comorbid with AD (BPI(-AD)) compared with healthy Controls.

Limitation: The low comorbidity rate of AD in both BP subtypes, especially BP-I, limit generalizing our findings.

Conclusion: The involvement of the dopaminergic pathway in AD was confirmed, particularly with BP-II rather than BP-I. Because the Val/Val genotype of the BDNF Val66Met polymorphism, rather than the other two polymorphisms, has been associated with anxiety, it seems to affect BP-I comorbid with AD without the involvement of the DRD3 Seg9Gly polymorphism, but may modify the involvement of DRD3 Gly/Gly in BP-II comorbid with AD.

Keywords: Anxiety comorbidity; BDNF; Bipolar subtypes; DRD3; Gene–gene interaction.