Variability in antidepressant response is due to genetic and environmental factors. Among genetic factors, the ones controlling for availability of the drug at the target site are interesting candidates. Rs6295C/G SNP for 5-HT1A gene (HTR1A) has been found to effect the expression and function of HTR1A In fact rs6295C/G was in strong linkage disequilibrium with other polymorphisms of HTR1A suggesting that those functional effects could be associated with polymorphisms other than the synonymous rs6295C/G. In the present study we examine the possible association of a panel of markers in strong linkage disequilibrium of the HTR1A with SSRI/SNRI response in 137 Japanese major depression sample followed for 6 weeks. We observed the significant association of better response to antidepressant with rs10042486C/C (p<0.0001), rs6295G/G (p<0.0001) and rs1364043T/T (p=0.018) genotype carriers, that is mutant allele homozygote, independently from clinical variables. Furthermore mutant allele homozygote carriers in all these 3 SNPs was associated more solidly with treatment response by various assessment such as HAM-D score change over time (p=0.001), week 2 (p<0.0001), 4(p=0.007), and 6(p=0.048) as well as response rate (p=0.0005) and remission rate (p=0.004).

In conclusion, this is the first study that reports the significant association of antidepressant response with rs10042486C/T and rs1364043G/T variants of HTR1A and also with rs10042486-rs6295-rs1364043 combination. This finding adds an important piece of information for the pathway of detecting the genetics of antidepressant response even if results must be verified on larger samples.