Common genes associated with antidepressant response in mouse and man identify key role of glucocorticoid receptor sensitivity
PLoS biology. Bd. 15. H. 12. Lawrence, KS: PLoS 2017 e2002690
Erscheinungsjahr: 2017
ISBN/ISSN: 1545-7885 ; 1544-9173
Publikationstyp: Zeitschriftenaufsatz
Sprache: Englisch
| Geprüft: | Bibliothek |
Inhaltszusammenfassung
Major depression is the second leading cause of disability worldwide. However, only one-third of patients with depression benefit from the first antidepressant compound they are prescribed. It is a fundamental problem that the outcomes of individual antidepressant treatments are still highly unpredictable. In clinical studies, discovery of biomarkers for antidepressant response is hampered by confounding factors such as the heterogeneity of the disease phenotype and additional environmental f...Major depression is the second leading cause of disability worldwide. However, only one-third of patients with depression benefit from the first antidepressant compound they are prescribed. It is a fundamental problem that the outcomes of individual antidepressant treatments are still highly unpredictable. In clinical studies, discovery of biomarkers for antidepressant response is hampered by confounding factors such as the heterogeneity of the disease phenotype and additional environmental factors, e.g., previous life events and different schedules of psychopharmacological treatment, which reduce the power to detect true response biomarkers. To overcome some of these limitations, we have established a conceptually novel approach that allows the selection of extreme phenotypes in an antidepressant-responsive mouse strain. In the first step, we identify signatures in the transcriptome of peripheral blood associated with responses following stratification into good and poor treatment responders. As proof of concept, we translate the murine data to a population of depressed patients. We show that differences in expression profiles from baseline to week 12 of the human orthologues predict response status in patients. We finally provide evidence that sensitivity of the glucocorticoid receptor could be a potential key mechanism shaping response to antidepressant treatment.» weiterlesen» einklappen
Autoren
Klassifikation
DDC Sachgruppe:
Medizin
