Reduced glucocorticoid receptors: consequence or cause of depression?
Trends in Endocrinology and MetabolismPublished 31 March 2006
Gretchen N. Neigh, Charles B. Nemeroff
Citations46
SJR quartileQ1
SJR score3.48
SNIP2.69
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
This model offers a novel system for the study of the pathophysiology that underlies depression-like behaviors and adds to the growing evidence that implicates glucocorticoid receptor dysfunction in depression.
Abstract
Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is common in patients with major depression. A recent study demonstrates that reduced expression of the glucocorticoid receptor in mice causes depression-like behaviors and HPA axis dysfunction following stressor exposure. This model offers a novel system for the study of the pathophysiology that underlies depression-like behaviors. It also adds to the growing evidence that implicates glucocorticoid receptor dysfunction in depression.
Keywords
MedicineNeuroscience
Archives of General PsychiatryA Molecular and Cellular Theory of Depression
2,108 Citations1997Ronald S. Duman
These findings constitute the framework for an updated molecular and cellular hypothesis of depression, which posits that stress-induced vulnerability and the therapeutic action of antidepressant treatments occur via intracellular mechanisms that decrease or increase, respectively, neurotrophic factors necessary for the survival and function of particular neurons.
Nature GeneticsDisruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
1,859 Citations1999François Tronche, Christoph Kellendonk +7 more
Conditional mutagenesis of Gr in the nervous system provides genetic evidence for the importance of Gr signalling in emotional behaviour because mutant animals show an impaired behavioural response to stress and display reduced anxiety.
ScienceElevated Concentrations of CSF Corticotropin-Releasing Factor-Like Immunoreactivity in Depressed Patients
1,487 Citations1984Charles B. Nemeroff, Erik Widerlöv +7 more
Findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.
Biological PsychiatryGlucocorticoid receptors in major depression: relevance to pathophysiology and treatment
1,140 Citations2001Carmine M. Pariante, Andrew H. Miller
The data support the hypothesis that the function of the GR is reduced in major depression in the absence of clear evidence of decreased GR expression and indicate that some antidepressants have direct effects on the GR, leading to enhanced GR function and increased GR expression.
Psychiatric Clinics of North AmericaPSYCHONEUROENDOCRINOLOGY OF DEPRESSION
662 Citations1998Paul M. Plotsky, Michael J. Owens +1 more
Functional assessment of the HPA axis is thought to provide a window into central nervous system operation that may be of diagnostic value in this and other affective disorders regardless of whether CRF and glucocorticoids are directly involved in the origin of major depression or merely exacerbate the consequences of other primary defects.
Archives of General PsychiatryThe Dexamethasone Suppression Test for Diagnosis and Prognosis in Psychiatry
531 Citations1985George W. Arana
A modified dexamethasone suppression test (DST) has had unprecedented evaluation among biologic tests proposed for clinical use in psychiatry, but it has not proved to reflect pathophysiologic changes at the level of the central nervous system or pituitary, and tissue availability of dexamETHasone itself may contribute to test outcome.
Journal of NeuroscienceMice with Genetically Altered Glucocorticoid Receptor Expression Show Altered Sensitivity for Stress-Induced Depressive Reactions
377 Citations2005Stephanie Ridder, Sabine Chourbaji +10 more
A downregulation of BDNF protein content in the hippocampus of GR+/- mice is identified, which is in agreement with the so-called neurotrophin hypothesis of depression, and can now be used to study biological changes underlying the pathogenesis of depressive disorders.
NeuroendocrinologyAltered Hypothalamic-Pituitary-Adrenocortical Regulation in Healthy Subjects at High Familial Risk for Affective Disorders
371 Citations2008Florian Holsboer, Christoph Lauer +2 more
This investigation investigated whether the HPA feedback disturbance observed among patients with depression is present in otherwise healthy individuals who are at high risk for psychiatric disorders because they have a first-degree relative with an affective illness.
Proceedings of the National Academy of SciencesAcquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior
365 Citations2004Maureen P. Boyle, Judson A. Brewer +5 more
It is suggested that imipramine's proposed activities on forebrain GR function are not essential for its antidepressant effects, and that alteration in GR expression may play a causative role in disease onset of major depressive disorder.
Proceedings of the National Academy of SciencesPoint mutation in the mouse glucocorticoid receptor preventing DNA binding impairs spatial memory
282 Citations2001Melly S. Oitzl, Holger M. Reichardt +2 more
Biological PsychiatryNew insights into the role of cortisol and the glucocorticoid receptor in severe depression
219 Citations2002Philip W. Gold, Wayne C. Drevets +2 more
The role of cortisol during the stress response and mechanisms by which cortisol can set into motion positive reverberatory feedback loops among brain regions regulating emotion and cognition relevant to mood disorders are discussed.
NeuropsychopharmacologyClinical and Biological Effects of Mifepristone Treatment for Psychotic Depression
204 Citations2005Benjamin Flores, Heather A. Kenna +3 more
The results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may re-regulate the HPA axis.
Journal of NeuroscienceIncreased Depression-Like Behaviors in Corticotropin-Releasing Factor Receptor-2-Deficient Mice: Sexually Dichotomous Responses
168 Citations2003Tracy L. Bale, Wylie Vale
The results may reveal an interaction of CRF pathways with other known antidepressant systems and may also support an involvement ofCRF receptors in the development of depression such that elevated CRFR1 activity, in the absence of CRFR2, increases depression-like behaviors.
American Journal of PsychiatryGlucocorticoid receptors in depression: relationship to the dexamethasone suppression test
133 Citations1985Glenn J. Gormley, M T Lowy +4 more
Changes in receptor concentration were positively correlated with postdexamethasone serum cortisol levels and with the inhibitory effect of dexameth asone on mitogen-induced lymphocyte proliferation.
Journal of NeuroscienceReduced Activity of Hypothalamic Corticotropin-Releasing Hormone Neurons in Transgenic Mice with Impaired Glucocorticoid Receptor Function
71 Citations1998Ivar Dijkstra, Fred J.H. Tilders +7 more
The data show that long-term GR dysfunction can be associated with reduced activity of CRH neurons in the PVN and decreased sensitivity of pituitary CRH-R1 mRNA to stimulus-induced downregulation, and suggest that impaired GR function, at least if present since early embryonic life, does not necessarily result in CRH hyperexpression characteristics of disorders such as major depression.
PubMedLymphocyte glucocorticoid receptor: predictor of sertraline response in adolescent major depressive disorder (MDD).
20 Citations1995Sallee Fr, Lisa Nesbitt +4 more
It is hypothesized that lymphocyte GCII is altered in adolescent MDD and could serve as a marker for response to SRIs.
The British Journal of PsychiatryDrug treatment for psychotic depression
2 Citations2006Joe John Vattakatuchery
I read the review article by Wijkstra et al with much interest as I found the results in the abstract quite striking, and raised a few points about the methodology and description of results.