Elsevier

Biological Psychiatry

Volume 63, Issue 12, 15 June 2008, Pages 1103-1110
Biological Psychiatry

Archival Report
The FKBP5-Gene in Depression and Treatment Response—an Association Study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort

https://doi.org/10.1016/j.biopsych.2007.10.026Get rights and content

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.

Section snippets

Patients and Study Design

This study presents data obtained from level 1 of the STAR*D study, whose overall study design has been described elsewhere (17, 18, 19). Diagnoses were established according to DSM-IV criteria, and only non-psychotic MDD was included. A diagnosis of bipolar disorder led to exclusion from the study.

The treatment regime at level 1 aimed to evaluate outcome of treatment with the antidepressant drug citalopram (18, 20). To reduce the risk of inadequate dosing and to ensure that patients who

Case-Control Study

In the comparison of cases and control subjects, nominally significant associations of markers rs1360780 and rs4713916 with disease were identified in the White non-Hispanic population in a genotype-wise test (Table 1). However, only the finding in rs1360780 remained significant after correction for multiple testing (p = .046). The CC-genotype was more frequent in control subjects than in cases (50% vs. 44%), whereas the TC-heterozygote genotype was over-represented in cases (46% vs. 38%). No

Case-Control Study

Sufficient power to detect association of genotype to phenotype can only be obtained with large sample sizes (29), especially when genes that only partially contribute to the disease susceptibility shall be identified. Furthermore, association signals must be strong enough to survive correction for multiple testing, as carried out in this study as well as in the original FKBP5-study.

The present case-control analysis was carried out including 1256 White non-Hispanic individuals matched with 634

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