INTRODUCTION: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a pathogenic mechanism of depression, and genetic polymorphisms in HPA axis genes have been described to influence response to antidepressant drugs. In particular, two polymorphisms in FKBP5, a co-chaperone of the glucocorticoid receptor, were strongly associated with response to therapy. We aimed to analyze whether these findings could be reproduced in a different sample of otherwise comparable inpatients with major depression. METHODS: Genotyping for the two variants within the FKBP5 gene was performed using PCR-restriction fragment length polymorphism and Taqman real-time PCR in a cohort of 179 inpatients who were monitored for the first 3 weeks of antidepressant drug treatment. The early response to antidepressant drugs was assessed as percentage of decline in Hamilton depression score after 3 weeks, responders versus nonresponders were distinguished by a 50% decrease. RESULTS: The FKBP5 variants rs3800373 and rs1360780 were highly linked, and carriers of the FKBP5 variants had a trend towards a higher chance to respond (p = 0.04; odds ratio: 1.8; 95% CI: 0.98-3.3). When analyzing drug-specific subgroups, the effect was seen mainly in the subgroups of patients treated with antidepressant drug combinations or with venlafaxine. CONCLUSION: In this study, an effect of FKBP5 variants on antidepressant drug response was confirmed in an independent cohort of depressed patients; however, with an odds ratio of 1.8 the effect size was smaller than that described earlier.
INTRODUCTION: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a pathogenic mechanism of depression, and genetic polymorphisms in HPA axis genes have been described to influence response to antidepressant drugs. In particular, two polymorphisms in FKBP5, a co-chaperone of the glucocorticoid receptor, were strongly associated with response to therapy. We aimed to analyze whether these findings could be reproduced in a different sample of otherwise comparable inpatients with major depression. METHODS: Genotyping for the two variants within the FKBP5 gene was performed using PCR-restriction fragment length polymorphism and Taqman real-time PCR in a cohort of 179 inpatients who were monitored for the first 3 weeks of antidepressant drug treatment. The early response to antidepressant drugs was assessed as percentage of decline in Hamilton depression score after 3 weeks, responders versus nonresponders were distinguished by a 50% decrease. RESULTS: The FKBP5 variants rs3800373 and rs1360780 were highly linked, and carriers of the FKBP5 variants had a trend towards a higher chance to respond (p = 0.04; odds ratio: 1.8; 95% CI: 0.98-3.3). When analyzing drug-specific subgroups, the effect was seen mainly in the subgroups of patients treated with antidepressant drug combinations or with venlafaxine. CONCLUSION: In this study, an effect of FKBP5 variants on antidepressant drug response was confirmed in an independent cohort of depressedpatients; however, with an odds ratio of 1.8 the effect size was smaller than that described earlier.
Authors: Erick T Tatro; Timothy B Nguyen; Chad A Bousman; Eliezer Masliah; Igor Grant; J Hampton Atkinson; Ian P Everall Journal: J Neurovirol Date: 2010-10 Impact factor: 2.643
Authors: Katrin Sangkuhl; Julia C Stingl; Miia Turpeinen; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2014-01 Impact factor: 2.089
Authors: Cheryl L Storer; Chad A Dickey; Mario D Galigniana; Theo Rein; Marc B Cox Journal: Trends Endocrinol Metab Date: 2011-08-31 Impact factor: 12.015
Authors: Katarzyna A Ellsworth; Irene Moon; Bruce W Eckloff; Brooke L Fridley; Gregory D Jenkins; Anthony Batzler; Joanna M Biernacka; Ryan Abo; Abra Brisbin; Yuan Ji; Scott Hebbring; Eric D Wieben; David A Mrazek; Richard M Weinshilboum; Liewei Wang Journal: Pharmacogenet Genomics Date: 2013-03 Impact factor: 2.089