A Genomewide Association Study of Citalopram Response in Major Depressive Disorder

Abstract

Background-Antidepressant response is likely influenced by genetic constitution, but the actual genes involved have yet to be determined. We have carried out a genome-wide association study to determine if common DNA variation influences antidepressant response.

Further evidence of an association between a genetic variant in BMP7 and treatment response to SSRIs in major depressive disorder

“…The main outcome of the mega-analysis 5 was remission after treatment with several antidepressants (for example, SSRIs, nortriptyline and others), which was defined as a HAM-D score o7 points. In our data set (number of patients in remission ¼ 84 (37.5%), which was less than those examined in the mega-analysis (41%) 5 and the STAR*D only (55%) 3 ), we failed to detect a significant association even with the BMP7 SNP (P ¼ 0.19, OR ¼ 0.77 (95% confidence interval 0.51-1.14)); thus, the uncontrolled bias in our study may have affected the results. In general, although there is a correlation between the categorical variables of 'responder' and 'remission,' several clinical or environmental factors are also likely to influence 'remission' more than 'responder' , as 'remission' requires a more stringent level.…”

“…To address this issue, in the current study, we performed a validation study on genetic associations using the Japanese population and a meta-analysis of single nucleotide polymorphisms (SNPs) detected in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 3 which was performed to determine the treatment efficacy of selective serotonin reuptake inhibitors (SSRIs) in MDD.…”

“…Detailed information on the clinical phenotypes is described elsewhere. 4 In the current study, however, we included only patients with a minimum depression severity score of 14 out of 17 items on the Hamilton Depressive Rating scale (HAM-D) and an age range from 18 to 75 years according to the inclusion criteria of STAR*D. 3 Of these patients, 104, 63 and 57 were treated with fluvoxamine, sertraline and paroxetine, respectively, for 8 weeks (monotherapy). The HAM-D scores were assessed in each patient at baseline (0 weeks: mean±s.d.…”

“…A responder was defined as a patient who showed a X50%reduction in HAM-D scores (number of responders ¼ 129, number of nonresponders ¼ 95), in accordance with previous studies. 3 SNPs were selected from the STAR*D study, in which the authors examined the association of genome-wide SNPs with citalopram (an SSRI) efficacy. In that study, no SNPs showed evidence at the genome-wide significance level, but the top three SNPs in responders (rs6966038, and rs6127921 and rs809736) 3 showing a suggestive association with a P-value o1 Â 10 À5 were analyzed in our current study (genotyped by TaqMan SNP genotyping (Life Technologies, Carlsbad, CA, USA) for rs6966038, and PCR-RFLP for rs6127921 and rs809736.…”

Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

“…The characteristics of this subsample and how they differed from the full sample have been detailed in earlier reports (McMahon et al, 2006;Laje et al, 2007;Perlis, 2007;Laje et al, 2009;Garriock et al, 2010). The genotyping and quality-control methods are extensively described elsewhere (Garriock et al, 2010;Cultler et al, 2012). Briefly, lymphocyte-or lymphoblastoid-derived DNA was genotyped on Affymetrix 500 K or 5.0 human SNP arrays (X99% concordance was observed in the 12 samples genotyped on both platforms).…”