Serotonin 2A Receptor Polymorphisms and [³H]Ketanserin Binding

To the Editor: The report by Gustavo Turecki, M.D., Ph.D., and colleagues (1), showing higher than normal [³H]ketanserin binding in the prefrontal cortex of suicide victims, extends the evidence for an involvement of the serotonin 2A (5-HT_2A) receptor in suicide and mood disorders. However, the finding of an association between the level of [³H]ketanserin binding and genetic variation of the receptor in the 22 brains studied conflicts with existing data. In two larger studies no relationship existed between prefrontal cortex [³H]ketanserin binding and either the T102C polymorphism (2) or the linked A-1438G polymorphism (3) (N=125 and N=122, respectively). As such, any effect of these genotypes on 5-HT_2A receptor expression must be considered unproved, and since both polymorphisms are silent, their functional significance remains obscure (4).