Stimulated Gene Expression Profiles as a Blood Marker of Major Depressive Disorder

Spijker, Sabine; Zanten, Jeroen S. van; Jong, Simone de; Penninx, Brenda W. J. H.; Dyck, Richard van; Zitman, Frans G.; Smit, Jan; Ylstra, Bauke; Smit, August B.; Hoogendijk, Witte J.G.

doi:10.1016/j.biopsych.2010.03.017

Cited by 103 publications

(77 citation statements)

References 56 publications

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“…The stimulated gene expression profiles outperformed baseline gene expression patterns, which only correctly classified 41.7% of individuals in the test cohort, even though a larger number of predictors was used in the analysis. This supports the previously described superiority of stimulated over baseline gene expression differences as biomarkers for depression (Spijker et al, 2010). Spijker et al (2010) investigated gene expression changes in peripheral blood monocytes following an ex vivo challenge with LPS, a strong immunogenic stimulus, which is less influenced by confounding variables than the here presented in vivo challenge test.…”

Section: Discussionsupporting

confidence: 87%

“…This supports the previously described superiority of stimulated over baseline gene expression differences as biomarkers for depression (Spijker et al, 2010). Spijker et al (2010) investigated gene expression changes in peripheral blood monocytes following an ex vivo challenge with LPS, a strong immunogenic stimulus, which is less influenced by confounding variables than the here presented in vivo challenge test. However, the reported sensitivity of 77% and specificity of 72% is in the range of the one reported in our study.…”

Section: Discussionsupporting

confidence: 87%

“…We therefore hypothesized that GR-stimulated gene expression would be different in in-patients with moderate to severe depressive symptoms as compared with healthy controls. A recent study by Spijker et al (2010) showing gene expression differences between cases and controls using an ex vivo lipopolysaccharide (LPS) challenge test supports the notion that stimulated gene expression measures are better at discriminating between patients and controls than baseline measures.…”

Section: Introductionmentioning

confidence: 95%

“…Additionally, glucocorticoids have effects on peripheral blood cells and the hypothalamus-pituitary adrenal (HPA) axis, which is perturbed during depressive episodes of many patients (Gladkevich et al, 2004). Transcriptional profiling in whole blood has been used in the search for biomarkers for patients with neurological and other psychiatric disorders including patients with Parkinson's (Scherzer et al, 2007) and Huntington's disease (Borovecki et al, 2005), post-traumatic stress disorder Segman et al, 2005;Yehuda et al, 2009), schizophrenia (Kurian et al, 2011), bipolar disorder (Le-Niculescu et al, 2009;Padmos et al, 2008) and major depression (Segman et al, 2010;Spijker et al, 2010). Most of these studies have analyzed baseline gene expression profiles.…”

Section: Introductionmentioning

confidence: 99%

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Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Menke

Arloth

Pütz

et al. 2012

Neuropsychopharmacol

146

126

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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 ¼ 18 cases/18 controls) and a test cohort (N ¼ 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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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Menke

Arloth

Pütz

et al. 2012

Neuropsychopharmacol

146

126

View full text Add to dashboard Cite

show abstract

“…Using LPS-stimulated blood samples, Spijker et al compared gene expression profiles between healthy and unmedicated patients with MDD. A significant difference in gene expression pattern was observed in a subset of genes, all of which have not been previously associated with depression (Spijker et al, 2010). Transcriptome changes in the leukocyte mRNA is correlated with response to antidepressant agents or lithium therapy (Iga et al, 2008).…”

Section: Gene Expression Signaturesmentioning

confidence: 92%

Biological Alterations in Depression

Benton¹,

Wiltshire²

2011

Psychiatric Disorders - Trends and Developments

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SUMO regulation of FKBP51 activity and the stress response

Gobbini

Velardo

Sokn

et al. 2023

J of Cellular Biochemistry

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Glucocorticoids (GCs) actions are mostly mediated by the GC receptor (GR), a member of the nuclear receptor superfamily. Alterations of the GR activity have been associated to different diseases including mood disorders. FKBP51 is a GR chaperone that has gained much attention because it is a strong inhibitor of GR activity. FKBP51 exerts effects on many stress‐related pathways and may be an important mediator of emotional behavior. Key proteins involved in the regulation of the stress response and antidepressant action are regulated by SUMOylation, a post‐translational modification that has an important role in the regulation of neuronal physiology and disease. In this review, we focus on the role of SUMO‐conjugation as a regulator of this pathway.

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Stimulated Gene Expression Profiles as a Blood Marker of Major Depressive Disorder

Cited by 103 publications

References 56 publications

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

Biological Alterations in Depression

SUMO regulation of FKBP51 activity and the stress response

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