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-HT2A) 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-HT2A receptor expression must be considered unproved, and since both polymorphisms are silent, their functional significance remains obscure (4).
1. Turecki G, Briere R, Dewar K, Antonetti T, Lesage AD, Seguin M, Chawky N, Vanier C, Alda M, Joober R, Benkelfat C, Rouleau GA: Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry 1999; 156:1456–1458Google Scholar
2. Kouzmenko AP, Hayes WL, Pereira AM, Dean B, Burnet PW, Harrison PJ:5-HT2A receptor polymorphism and steady state receptor expression in schizophrenia (letter). Lancet 1997; 349:1815Google Scholar
3. Kouzmenko AP, Scaffidi A, Pereira AM, Hayes WL, Copolov DL, Dean B: No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter and the density of frontal cortical 5-HT2A receptors in schizophrenia. Hum Hered 1999; 49:103–105Crossref, Medline, Google Scholar
4. Harrison PJ, Burnet PW: The 5-HT2A (serotonin2A) receptor gene in the aetiology, pathophysiology and pharmacotherapy of schizophrenia. J Psychopharmacol 1997; 11:18–20Crossref, Medline, Google Scholar
