Association of 5-HT2A receptor gene polymorphism with major affective disorders: the case of a subgroup of bipolar disorder with low suicide risk

Background: The implication of serotonin in suicide and affective disease explains why the 5-HT2A receptor gene has been proposed as a candidate gene in these disorders, although with conflicting results. Methods: We analysed the distribution of the 5-HT2A–1438A/G genetic polymorphism in 192 patients with major affective disorder (127 bipolar disorders and 65 unipolar disorders) compared to 142 healthy control subjects. Results: We found a higher frequency of the A allele in affected patients than in control subjects (p = .034), this difference being particularly striking for the subgroup of patients with type I bipolar disorder (p = .015). Patients with no personal and/or familial history of suicide attempts mainly accounted for the excess of the A allele in affected patients. Conclusions: The association detected in this study suggests that the 5-HT2A receptor gene may play a role in the genetic susceptibility to bipolar disorder, through a specific subgroup of bipolar type I patients with lower risk of suicidal behavior.