Revisiting the Dexamethasone Suppression Test in unipolar major depression: an exploratory study

Fountoulakis, Konstantinos Ν.; Gonda, Xénia; Rihmer, Zoltán; Fokas, Costas; Iacovides, Apostolos

doi:10.1186/1744-859x-7-22

Cited by 30 publications

(17 citation statements)

References 39 publications

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“…In fact, 3 (30%) out of 10 patients not suppressed at the dexamethasone suppression test; this percentage is consistent with most of the data reported in the literature. Vasavada and collaborators showed that non suppression occurred in 27% of patients with MDD and in 43% of bipolar patients during depression phase [13]; similar data have been reported by the group of Iacovides [12].…”

Section: Discussionsupporting

confidence: 68%

“…Patients with MDD have elevated cortisol levels in plasma as well as elevated cortisol response to combined test dexamethasone/CRH [11]. However, the activation of HPA axis in depressed patients appears to be dependent on several factors, including melancholic and atypical features, chronicity, cytokine involvement and genetic traits; therefore, depressed patients do not show an HPA axis hyperactivity in as much as 27–32% of the cases [12], [13].…”

Section: Introductionmentioning

confidence: 99%

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Monocytes from Depressed Patients Display an Altered Pattern of Response to Endotoxin Challenge

Lisi¹,

Camardese²,

Treglia³

et al. 2013

PLoS ONE

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It is now well established that major depression is accompanied and characterized by altered responses of the immune-inflammatory system. In this study we investigated the pro-inflammatory activation of monocytes isolated from depressed patients as a parameter not influenced by such confounds as the time of day, the nutritional and exercise status or the age and gender of patients. Monocytes from depressed patients and from healthy controls were isolated in vitro; after 24-h incubation under basal conditions, cells were exposed for 24-h to 100 ng/ml of endotoxin (bacterial lipopolysaccharide, LPS). We found that monocytes from drug-free depressed patients and controls release the same amounts of prostaglandin E2 (PGE2) under basal conditions, whereas monocytes from patients are dramatically less reactive to LPS (8.62-fold increase vs previous 24 hrs) compared to healthy controls (123.3-fold increase vs previous 24 hrs). Such blunted prostanoid production was paralleled by a reduction in COX-2 gene expression, whereas other pro-inflammatory mediators, namely interleukin-1β (IL-1 β) and -6 (IL-6) showed a trend to increased gene expression. The above changes were not associated to increased levels of circulating glucocorticoids. After 8 months of antidepressive drug treatment, the increase in PGE2 production after the endotoxin challenge was partially restored, whereas the increase in IL-1 β and -6 levels observed at baseline was completely abolished. In conclusion, our findings show that the reactivity of monocytes from depressed patients might be considered as a marker of the immune-inflammatory disorders associated to depression, although the lack of paired healthy controls at follow-up does not allow to conclude that monocyte reactivity to endotoxin is also a marker of treatment outcome.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Monocytes from Depressed Patients Display an Altered Pattern of Response to Endotoxin Challenge

Lisi¹,

Camardese²,

Treglia³

et al. 2013

PLoS ONE

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show abstract

“…This is partly supported by a study on unipolar depression showing that patients exhibiting hypercortisolism had higher GAF scores than the rest, which consisted of unknown fractions of patients exhibiting eucortisolism and hypocortisolism [39]. There are no other comparable studies that can shed light on this association and the results are in need of replication and a more detailed investigation.…”

Section: Discussionmentioning

confidence: 93%

Relative Hypo- and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder: A Cross-Sectional Study

et al. 2014

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BackgroundDepression in unipolar and bipolar disorders is associated with hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity. Also, unipolar disorder has recently been shown to exhibit HPA-axis hypoactivity. We studied for the first time how HPA-axis hypo- and hyperactivity relate to depression and disease burden in bipolar disorder. We were interested in studying hypocortisolism; characterized by increased HPA-axis negative feedback sensitivity and lower basal cortisol levels together with the opposite HPA-axis regulatory pattern of hypercortisolism.MethodsThis cross-sectional study includes 145 type 1 and 2 bipolar outpatients and 145 matched controls. A dexamethasone-suppression-test (DST) measures the negative feedback sensitivity and a weight-adjusted very-low-dose DST was employed, which is sensitive in identifying hypocortisolism and hypercortisolism. The 25th and 75th percentiles of control post-DST values were used as cut-offs identifying patients exhibiting relative hypo-, and hypercortisolism. Self-report questionnaires were employed: Beck-Depression-Inventory (BDI), Montgomery-Åsberg-Depression-Rating-Scale (MADRS-S), World-Health-Organization-Quality-of-Life-Assessment–100 and Global-Assessment-of-Functioning.ResultsPatients exhibiting relative hypocortisolism expectedly exhibited lowered basal cortisol levels (p = 0.046). Patients exhibiting relative hypercortisolism expectedly exhibited elevated basal levels (p<0.001). Patients exhibiting relative hypocortisolism showed 1.9–2.0 (BDI, p = 0.017, MADRS-S, p = 0.37) and 6.0 (p<0.001) times increased frequencies of depression and low overall life quality compared with patients exhibiting mid post-DST values (eucortisolism). Adjusted Odds Ratios (OR:s) for depression ranged from 3.8–4.1 (BDI, p = 0.006, MADRS-S, p = 0.011) and was 23.4 (p<0.001) for life quality. Patients exhibiting relative hypercortisolism showed 1.9–2.4 (BDI, p = 0.017, MADRS-S, p = 0.003) and 4.7 (p<0.001) times higher frequencies of depression and low overall life quality compared with patients exhibiting eucortisolism. Adjusted OR:s for depression ranged from 2.2–2.7 (BDI, p = 0.068, MADRS-S, p = 0.045) and was 6.3 (p = 0.008) for life quality.LimitationsThe cross-sectional design and lack of pre-established reference values of the DST employed.ConclusionsRelative hypocortisolism and relative hypercortisolism were associated with depression and lower life quality, providing novel insights into the detrimental role of stress in bipolar disorder.

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“…The hyperactivity of the hypothalamic-pituitaryadrenal axis has an important role in the psychobiology of depression (11,12). But as a correlate of melancholia, the dexhametasone suppression test (DST), whether or not fail to suppress plasma cortisol, may be lacking sufficient sensitivity or specificity for an accurate diagnosis of melancholia.…”

Section: Discussionmentioning

confidence: 99%

Diagnosis and Classification Subtyping of Depressive Disorders: Comparison of Three Methods

Örsel

Karadağ

Türkçapar³

et al. 2010

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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Revisiting the Dexamethasone Suppression Test in unipolar major depression: an exploratory study

Abstract: Background: Important methodological questions still exist concerning the Dexamethasone Suppression Test (DST), including the possibility of a better way of interpreting it. The aim of the present study was to explore the feasibility of an alternative way of interpreting DST results.

Cited by 30 publications

References 39 publications

Monocytes from Depressed Patients Display an Altered Pattern of Response to Endotoxin Challenge

Monocytes from Depressed Patients Display an Altered Pattern of Response to Endotoxin Challenge

Relative Hypo- and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder: A Cross-Sectional Study

Diagnosis and Classification Subtyping of Depressive Disorders: Comparison of Three Methods

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