Glucocorticoid resistance in depression: the dexamethasone suppression test and lymphocyte sensitivity to dexamethasone

Mt, Lowy; At, Reder; Antel, Jack P.; Hy, Meltzer

doi:10.1176/ajp.141.11.1365

Cited by 96 publications

(4 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antidepressants appear to potentiate the effects of corticosteroids (46). A subset of depressed patients (47) and asthma patients (48) demonstrate resistance to glucocorticoids. Although highly speculative, antidepressants may decrease resistance to the effects of this type of medication.…”

Section: Discussionmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled Trial of Escitalopram in Patients with Asthma and Major Depressive Disorder

Brown

Sayed

Enkevort

et al. 2018

The Journal of Allergy and Clinical Immunology: In Practice

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled Trial of Escitalopram in Patients with Asthma and Major Depressive Disorder

Brown

Sayed

Enkevort

et al. 2018

The Journal of Allergy and Clinical Immunology: In Practice

View full text Add to dashboard Cite

show abstract

“…Changes in GR expression, nuclear translocation, co-factor binding and GR-mediated gene transcription may play a fundamental role in altered HPA axis responsiveness to glucocorticoids in the HPA axis tissues, which may contribute to HPA axis hyperactivity. Indeed, studies on immune cells from peripheral blood have shown that the capacity of glucocorticoids to inhibit proliferation of PBMCs in response to polyclonal mitogens is impaired in depressed patients (Lowy et al, 1984; Wodarz et al, 1991; Pariante and Miller, 2001). These findings correlate with the findings in the DST discussed above, in that patients who are non-suppressors of the DST, and thus glucocorticoid resistant, also show reduced dexamethasone-induced inhibition of the lymphocyte proliferative response, and thus impaired GR function (Wodarz et al, 1991).…”

Section: The Gr In Depressionmentioning

confidence: 99%

The glucocorticoid receptor: Pivot of depression and of antidepressant treatment?

Anacker

Zunszain

Carvalho

et al. 2011

Psychoneuroendocrinology

522

342

View full text Add to dashboard Cite

Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and increased levels of glucocorticoid hormones in patients with depression have mostly been ascribed to impaired feedback regulation of the HPA axis, possibly caused by altered function of the receptor for glucocorticoid hormones, the glucocorticoid receptor (GR). Antidepressants, in turn, ameliorate many of the neurobiological disturbances in depression, including HPA axis hyperactivity, and thereby alleviate depressive symptoms. There is strong evidence for the notion that antidepressants exert these effects by modulating the GR. Such modulations, however, can be manifold and range from regulation of receptor expression to post-translational modifications, which may result in differences in GR nuclear translocation and GR-dependent gene transcription. The idea that the therapeutic action of antidepressants is mediated, at least in part, by restoring GR function, is consistent with studies showing that decreased GR function contributes to HPA axis hyperactivity and to the development of depressive symptoms. Conversely, excessive glucocorticoid signalling, which requires an active GR, is associated with functional impairments in the depressed brain, especially in the hippocampus, where it results in reduced neurogenesis and impaired neuroplasticity. In this review, we will focus on the GR as a key player in the precipitation, development and resolution of depression. We will discuss potential explanations for the apparent controversy between glucocorticoid resistance and the detrimental effects of excessive glucocorticoid signalling. We will review some of the evidence for modulation of the GR by antidepressants and we will provide further insight into how antidepressants may regulate the GR to overcome depressive symptoms.

show abstract

“…Importantly, our results demonstrated that 4-PSQ treatment was able to attenuate the activation of the HPA axis by reducing the plasma corticosterone levels, with an effect similar and superior to positive controls used in this study (paroxetine and donepezil, respectively). It is known that deregulation of the HPA axis causes the binding of cortisol to its glucocorticoid receptors and mineralocorticoid receptors in the limbic system, mainly in the hippocampus and prefrontal cortex that have a high density of these receptors (Lowy et al 1984 ). Consequently, neuronal atrophy occurs in these regions, resulting in emotional changes and memory dysfunction, symptoms that are found in patients with depression and AD (Lupien et al 2009 ; Colciago et al 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Prospecting for a quinoline containing selenium for comorbidities depression and memory impairment induced by restriction stress in mice

et al. 2022

View full text Add to dashboard Cite

Rationale Depression is often associated with memory impairment, a clinical feature of Alzheimer’s disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system. Objectives The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated. Methods ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1β, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus. Results 4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation. Conclusions These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities.

show abstract

Glucocorticoid resistance in depression: the dexamethasone suppression test and lymphocyte sensitivity to dexamethasone

Cited by 96 publications

References 18 publications

A Randomized, Double-Blind, Placebo-Controlled Trial of Escitalopram in Patients with Asthma and Major Depressive Disorder

A Randomized, Double-Blind, Placebo-Controlled Trial of Escitalopram in Patients with Asthma and Major Depressive Disorder

The glucocorticoid receptor: Pivot of depression and of antidepressant treatment?

Prospecting for a quinoline containing selenium for comorbidities depression and memory impairment induced by restriction stress in mice

Contact Info

Product

Resources

About