Bipolar disorder (BP), especially bipolar II disorder (BP-II), is highly comorbid with anxiety disorder (AD). Monoaminergic dysfunction has been implicated in the pathogenesis of BP, it may be important to investigate genes such as the catechol-O-methyltransferase (COMT), involved in monoamine metabolism and brain-derived neurotrophic factor (BDNF) genes, modulating the monoamine system. We therefore examined the association of the COMT Val158Met and BDNF Val66Met polymorphisms with BP-II with and without comorbidity of AD, and possible interactions between these genes. Seven hundred and seventy-one participants were recruited: 314 with bipolar-II without AD, 117 with bipolar-II with AD, and 340 healthy controls. The genotypes of the COMT and BDNF polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant effect of the COMT and the BDNF polymorphisms, and a significant interaction effect for the Val/Val genotypes of the BDNF Val66Met polymorphism and the COMsT Val158Met Val/Met and Met/Met genotypes (P=0.007, 0.048) discriminated between BP-II without AD patients and controls. Our findings provide initial evidence that the COMT and BDNF genes interact in bipolar-II without AD. Our findings suggest the involvement of dopaminergic pathway in the pathogenesis of bipolar-II.
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