Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment
| Autor: | S. R. Seaman, N. Kern, Bertram Müller-Myhsok, Tim M. Strom, Brigitta Bondy, Florian Holsboer, Thomas C. Baghai, Peter Zill, Manfred Uhr, Peter Lichtner, Thomas Meitinger, Tanja Brückl, Heike E. Künzel, Susanne Lucae, Daria Salyakina, Thomas Messer, Benno Pütz, Roselind Lieb, Sieglinde Modell, Andrea Pfennig, G. M. Wochnik, Oliver Köhnlein, Jakob C. Mueller, J. Brunner, Hildegard Pfister, Sergi Papiol, B. Fuchs, M. Majer, Theo Rein, N. Müller, Elin Lõhmussaar, Thomas Bettecken, Rainer Rupprecht, Elisabeth B. Binder, Thomas Nickel, Martin A. Kohli, Heike Dabitz, Tobias Deiml, Marcus Ising |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
medicine.medical_specialty Hypothalamo-Hypophyseal System Genotype Corticotropin-Releasing Hormone Vasopressins Blotting Western Pituitary-Adrenal System Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Fluorescence Glucocorticoid receptor Receptors Glucocorticoid Gene Frequency Internal medicine Germany Genetics medicine Humans HSP90 Heat-Shock Proteins Lymphocytes Protein Precursors Allele frequency Neurophysins Analysis of Variance Depression Reverse Transcriptase Polymerase Chain Reaction Antidepressive Agents Endocrinology Mechanism of action Antidepressant Regression Analysis Analysis of variance FKBP5 medicine.symptom Glucocorticoid medicine.drug |
| Zdroj: | Nature genetics. 36(12) |
| ISSN: | 1061-4036 |
| Popis: | The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. 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. |
| Databáze: | OpenAIRE |
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