Response to citalopram is not associated with SLC6A4 genotype in African-Americans and Caucasians with major depression

Abstract

Aims: Ethnic differences in genotype frequency provide a natural condition for assessing the contribution of gene variations to the causes and treatments of disease. Accordingly, the purpose of this study was to determine whether ethnic variations in allele frequencies of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene were related to the response to the treatment of depression.

Main methods: African-Americans (n=101) and Caucasians (n=100) with major depressive disorder were treated with the antidepressant citalopram (20-60mg/day) for 8weeks. Genotyping for the long (L) and short (s) alleles (LL, Ls, and ss) of the SLC6A4 gene was performed and the association between genotype and treatment response was assessed.

Key findings: Subjects in both ethnic groups showed a significant reduction in depression scores over time (p<.0001). However, in spite of a significantly greater frequency of the L allele in African-Americans as compared to Caucasians, a comparable clinical response between the two groups was found with 5-HTTLPR polymorphism not significantly associated with clinical response in either ethnic group.

Significance: The results are consistent with a previous finding and in accord with most of the results obtained in Caucasian subjects that SLC6A4 genotype is not related, at least by itself, to a response to treatment in either ethnic group to any clinically significant degree.

Trial registration: ClinicalTrials.gov NCT00047671.

Figure 1

Effect of treatment with CIT (20–60 mg/day) for eight weeks on HAM-D scores in African-American (AA) (n = 127) and Caucasian (C) (n = 114) subjects with major depression stratified by SLC6A4 genotype (LL, Ls, ss); The graphs are for the ITT group (n=241). There were no significant ethnic by genotype differences in treatment response in either the combined group or in each ethnic group analyzed separately (all p values >1.0) (see results section for details). Top graph shows HAM-D scores in AA and C subjects combined separated by genotype; Middle graph shows HAM-D scores in AA subjects separated by genotype; Bottom graph shows HAM-D scores in C subjects by genotype.