ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
Dexamethasone stimulated gene expression in peripheral blood is a sensitive marker for glucocorticoid receptor resistance in depressed patients.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 96 papers, 1 of them a synthesis that pooled it.
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.
- Evaluation of gene expression classification studies: factors associated with classification performance.PloS one · 2014Pooled it
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- In vivo effects of dexamethasone on blood gene expression in ataxia telangiectasia.Molecular and cellular biochemistry · 2018Trial
- Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline 'predictors' and longitudinal 'targets'.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Trial
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- SKA2 enhances stress-related glucocorticoid receptor signaling through FKBP4-FKBP5 interactions in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Response strategies to acute and chronic environmental stress in the arctic breeding Lapland longspur (Calcarius lapponicus).Communications biology · 2024Article
- Comparative Analysis of the Effects of Maternal Hypoxia and Placental Ischemia on HIF1-Dependent Metabolism and the Glucocorticoid System in the Embryonic and Newborn Rat Brain.International journal of molecular sciences · 2024Article
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- HPA flexibility andPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Development of novel liver-targeting glucocorticoid prodrugs.Medicine in drug discovery · 2024Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although gene expression profiles in peripheral blood in major depression are not likely to identify genes directly involved in the pathomechanism of affective disorders, they may serve as biomarkers for this disorder. As previous studies using baseline gene expression profiles have provided mixed results, our approach was to use an in vivo dexamethasone challenge test and to compare glucocorticoid receptor (GR)-mediated changes in gene expression between depressed patients and healthy controls. Whole genome gene expression data (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) from two independent cohorts were analyzed to identify gene expression pattern that would predict case and control status using a training (N=18 cases/18 controls) and a test cohort (N=11/13). Dexamethasone led to reproducible regulation of 2670 genes in controls and 1151 transcripts in cases. Several genes, including FKBP5 and DUSP1, previously associated with the pathophysiology of major depression, were found to be reliable markers of GR-activation. Using random forest analyses for classification, GR-stimulated gene expression outperformed baseline gene expression as a classifier for case and control status with a correct classification of 79.1 vs 41.6% in the test cohort. GR-stimulated gene expression performed best in dexamethasone non-suppressor patients (88.7% correctly classified with 100% sensitivity), but also correctly classified 77.3% of the suppressor patients (76.7% sensitivity), when using a refined set of 19 genes. Our study suggests that in vivo stimulated gene expression in peripheral blood cells could be a promising molecular marker of altered GR-functioning, an important component of the underlying pathology, in patients suffering from depressive episodes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.