Prediction of level of serotonin 2A receptor binding by serotonin receptor2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide

Objective: Postmortem studies have indicated that suicide victims have grea ter serotonin receptor 2A (5-HTR2A) binding in prefrontal brain regions. Ho wever, there remains some controversy regarding the biological specificity of these findings. The authors hypothesized that the variance observed in b rain 5-HTR2A binding is genetically mediated, at least in part. Method: Pos tmortem data from 56 subjects who had committed suicide and 126 normal comp arison subjects were studied; brain tissue was available from 11 subjects w ho committed suicide and 11 comparison subjects. Homogenate binding assays were carried out with [H-3]ketanserin. Variation at the 5-HTR2A gene (HTR2A ) was investigated by means of two polymorphisms: T102C and A-1438G. Result s: 5-HTR2A binding was greater in the prefrontal cortex of the subjects who committed suicide. In addition, the findings suggest that HTR2A variation significantly affects 5-HTR2A binding. However, no interaction between suic idal behavior and this locus was observed. Conclusions: These results confi rm previous reports of greater 5-HTR2A binding in subjects who committed su icide; they also provide preliminary evidence suggesting that the number of 5-HTR2A receptors is genetically mediated.