The FKBP5-gene in depression and treatment response--an association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort

Abstract

Background: In a recent study of several antidepressant drugs in hospitalized, non-Hispanic White patients, Binder et al. reported association of markers located within the FKBP5 gene with treatment response after 2 and 5 weeks. Individuals homozygous for the TT-genotype at one of the markers (rs1360780) reported more depressive episodes and responded better to antidepressant treatment. There was no association between markers in FKBP5 and disease. The present study aimed at studying the associated FKBP5 markers in the ethnically diverse Sequenced Treatment Alternatives to Relieve Depression (STAR*D) sample of non-hospitalized patients treated with citalopram.

Methods: We used clinical data and DNA samples from 1809 outpatients with non-psychotic major depressive disorder (DSM-IV criteria), who received up to 14 weeks of citalopram. A subset of 1523 patients of White non-Hispanic or Black race was matched with 739 control subjects for a case-control analysis. The markers rs1360780 and rs4713916 were genotyped on the Illumina platform. TaqMan-assay was used for marker rs3800373.

Results: In the case-control analysis, marker rs1360780 was significantly associated with disease status in the White non-Hispanic sample after correction for multiple testing. A significant association was also found between rs4713916 and remission. Markers rs1360780 and rs4713916 were in strong linkage disequilibrium in the White non-Hispanic but not in the Black population. There was no significant difference in the number of previous episodes of depression between genotypes at any of the three markers.

Conclusions: These results indicate that FKBP5 is an important target for further studies of depression and treatment response.

Figure 1

QIDS-C₁₆ scores by genotype over time measured in the White non-Hispanic population. After correction for multiple testing no significant difference in outcome of treatment response were seen when analyzed with one-way ANOVA. A; marker rs1360780. B; marker rs4713916. C; marker rs3800373.

Figure 2

Number of previous episodes of depression in the past, genotype-wise. No significant difference in the number of episodes of depression between genotypes was seen in any of the markers. Between markers where columns differ in size, mean and S.E.M. values are presented. A: All ethnic groups (n=1534). Mean and S.E.M values for TT- and TC-genotypes in the marker rs1360780; 4.28, 0.38 and 4.98, 0.20. Mean and S.E.M.. values for AA- and AG-genotypes at the marker rs4713916; 3.91, 0.43 and 5.0, 0.21. B: White non-Hispanic population (n=1117). Mean and S.E.M values for TT- and TC-genotypes in the marker rs1360780; 4.04, 0.43 and 4.75, 0.23. Mean and S.E.M. values for AA- and AG-genotypes in the marker rs4713916; 3.70, 0.49 and 4.69, 0.23. C: Black population (n=189). Mean and S.E.M values for TT- and TC-genotypes in the marker rs1360780; 5.19, 1.27 and 6.12, 0.61. Mean and S.E.M. values for AA- and AG-genotypes in the marker rs4713916; 3.68, 1.02 and 6.25 and 0.72. Mean and S.E.M. values for AA- and AC-genotypes in the marker rs3800370; 5.14, 0.65 and 6.33, 0.68.