Serotonin-2A-receptor and -transporter polymorphisms: lack of association in patients with major depression

Disturbances in serotonergic neurotransmission system have been implicated in the etiology of mood disorders. As the importance of genetic factors is well established, genes encoding for proteins of the serotonergic pathway a re important candidates to unravel the underlying genetic contribution. We examined two polymorphisms in the serotonin-2A-receptor gene (5-HT2A; T102C and His452Tyr) and the insertion/deletion polymorphism in the promoter reg ion of the serotonin transporter (5-HTTLPR) in a sample of 173 patients wit h major depression and 121 healthy controls. No statistical significant dif ferences between patients and controls were found for any of the three inve stigated polymorphisms, neither in the distribution of the genotypes nor in allele frequencies. However, concerning the 5-HTTLPR polymorphism, the fre quency of S/S (short allele) homozygotes was higher (23.1%) than in the con trol group (14.0%), but this failed to reach significance. Moreover we obse rved a different treatment response in patients with one or two C-alleles o f the T102C polymorphism, with a significantly higher decrease in HAMD-17 ( ANOVA: d.f. = 1, F = 5, 288, P = 0.023) after 4 weeks of antidepressant tre atment. Overall our results suggest that the investigated 5-HT2A a nd 5-HTT LPR polymorphisms are not major susceptibility factors in the etiology of m ajor depression. However, subtypes might be identified at least on a basis of differential treatment response. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.