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Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment

Binder, E. B. and Salyakina, D. and Lichtner, P. and Wochnik, G. M. and Ising, M. and Pütz, B. and Papiol, S. and Seaman, S. and Lucae, S. and Kohli, M. A. and Nickel, T. and Künzel, H. E. and Fuchs, B. and Majer, M. and Pfennig, A. and Kern, N. and Brunner, J. and Modell, S. and Baghai, T. and Deiml, T. and Zill, P. and Bondy, B. and Rupprecht, R. and Messer, T. and Köhnlein, O. and Dabitz, H. and Brückl, T. and Müller, N. and Pfister, H. and Lieb, R. and Mueller, J. C. and Lohmussar, E. and Strom, T. and Bettecken, T. and Meitinger, T. and Uhr, M. and Rein, T. and Holsboer, F. and Müller-Myhsok, B.. (2004) Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nature genetics, Vol. 36, H. 12. pp. 1319-1325.

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Official URL: http://edoc.unibas.ch/dok/A5253407

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Abstract

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality1 as well as the treatment of depression(2). To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.
Faculties and Departments:07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Klinische Psychologie und Epidemiologie (Lieb)
UniBasel Contributors:Lieb, Roselind
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publ.
ISSN:1061-4036
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:25
Deposited On:22 Mar 2012 13:43

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