The overwhelming majority of these studies involve treatment with the SSRIs. SSRIs Three studies suggest that patients with a specific polymorphism (A218C) in the gene coding for the TPH enzyme may respond more poorly to SSRIs than those without such a polymorphism,82-84 although this was not confirmed in three other studies.85-88 Early on, the results of some88-98 but not all99,103 studies also suggested that depressed patients with a certain (insertion/deletion) #find more keyword# polymorphism located in the promoter region of the gene coding for the serotonin transporter (5 HTTPR) have a relatively poorer response to the SSRIs than those without. Several

pooled analyses and meta-analyses have subsequently confirmed a predictive role for 5HTTPR genotype with regards to SSRI response in MDD, more so for Caucasian than Asian patients.104-106 More recently, however, Kraft, et al107 and, subsequently, Hu et al108 did not find an association between response to the SSRI

citalopram and 5 HTTPR genotype among 1914 subjects who Inhibitors,research,lifescience,medical participated in the first level of the STAR*D trial. This report, provides the strongest, evidence to date against Inhibitors,research,lifescience,medical a role for variation at this gene as a factor predicting clinical response to the SSRIs. Similarly, there have been conflicting reports regarding the role of 5-HT2-receptor genotype as a predictor of SSRI response. Specifically, two studies have identified Inhibitors,research,lifescience,medical a specific single nucleotide polymorphism (SNP) in the promoter region of the 5-HT2 receptor (A1438G) that appears to predict response to the SSRIs in MDD.91,109 However, this finding was not confirmed in a third report.110 More recently, however, McMahon et al111 conducted an analysis of numerous candidate genes as potential predictors of response to Inhibitors,research,lifescience,medical open-label

citalopram in MDD utilizing the STAR*D level-1 dataset (n=1953). Of 68 candidate genes investigated, only genetic variation at the locus coding for the 5-HT7 receptor gene was found to consistently predict clinical outcome,111 with differences MTMR9 in genotype (comparison of two homozygous groups) accounting for an 18% difference in the absolute risk of having no response to treatment. Relatively fewer studies have focused on genes coding for proteins not directly related to the monoaminergic system. Using a STAR*D-based dataset, Pcrlis et al112 demonstrated a relationship between the presence of a variant (KCNK2) in a gene (TREK1) coding for a potassium channel and the likelihood of experiencing symptom improvement, following treatment of MDD with the SSRI citalopram. In a separate study, Paddock et al113 reported that genetic variation in a kainic acid-type glutamate receptor was associated with response to the antidepressant citalopram (marker (rsl954787) in the GRIK4 gene, which codes for the kainic acid-type glutamate receptor KA1).