The role of BDNF genetic polymorphisms in bipolar disorder with psychiatric comorbidities

Abstract: Background: Bipolar disorder (BD) is a complex disorder where genetic factors play a major role in its etiology. Probably, no other axis I diagnosis has a co-morbidity prevalence as high as BD. Since BDNF is involved in different ways in various psychiatric disorders we hypothesized that its genetic polymorphisms could be associated with the co-morbidity phenomenon in BD. Methods: We studied 320 subjects (160 BD patients and 160 healthy controls). Genotyping was performed using made-to-order TaqMan genotyping assays (rs4923463, rs6265, rs2049045, and rs7103411). Statistical analyses were performed using UNPHASED version 3.0.12 and Haploview 4.1. Results: No genotypic, allelic or haplotype differences were found between bipolar patients and healthy controls. Concerning exclusively the rs4923463 (G/G) there was a significant association with alcoholism (p=0.009), smoking (p=0.006) and violent suicide attempt (p=0.03). We further found that the G-G haplotype (rs4923463–rs2049045) (adjusted p=0.029) and the G-T haplotype (rs4923463–rs7103411) (adjusted p=0.029) were significantly more frequent in the group with alcoholism co-morbidity when compared with the group without this co-morbidity. Limitations: Sample size and retrospective assessment of suicide behavior and psychiatric comorbidities. Conclusions: The results obtained in our study indicate that BDNF variants may confer susceptibility to additional psychiatric diagnosis in BD. [Copyright &y& Elsevier]