Epidemiological and genetic findings suggest comorbid anxiety disorders may help to define more genetically homogeneous forms of bipolar disorder (BD). Recent family-genetic studies suggest that BD with comorbid anxiety disorder constitutes a distinct clinical entity.We have previously shown that social phobia (SP) was linked to a more severe phenotype ofBDwith a higher rate of suicide attempts. SP could therefore be a component of this particular genetic subtype of BD and increase the association strength between BD and genes that have already been suspected in that disorder. The serotonin system has been implicated in the etiology of BD. In this study, polymorphisms of tryptophan hydroxylase (TPH) genes 1 and 2 were compared in BD patients with or without SP.
Method: Genotype and allele frequencies of TPH1 polymorphisms (rs7310929, rs211104, rs1800532 and a 50UTR microsatellite) and TPH2 polymorphisms (rs11178997, rs11179000, rs11179001, rs1386496, rs7305115, and rs1487279) were compared in all BD subjects (N¼453), BD subjects with SP (N¼58), without SP (N¼395) and controls (N¼478) using a chi-square test.
Results: TPH1 rs1800532 and 50UTR microsatellite were significantly associated with BD. However, this association was not strengthened by comorbid SP. Haplotype constructions showed that the more common TPH1 haplotpype was significantly associated with BD. However, this association was not influenced by comorbid SP.
Conclusion: Our results support previous findings suggesting association between TPH and BD. However, they did not show that SP could represent a BD genetic subtype preferentially associated with these genes.