A multisite trial of mifepristone for the treatment of psychotic depression: A site-by-treatment interaction

Blasey, Christine; DeBattista, Charles; Roe, Robert L.; Block, Thaddeus; Belanoff, Joseph K.

doi:10.1016/j.cct.2009.03.001

Cited by 53 publications

(28 citation statements)

References 15 publications

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“…In modern literature, black bile has been replaced by cortisol of which the brain effects are studied by a myriad of researchers throughout the world. However, the therapeutic efficacy of inhibitors of cortisol synthesis or antagonists of glucocorticoid receptor activity has not yet fulfilled its premises in psychiatry (Blasey et al 2009; Kling et al 2009) and the pathogenesis of depression still remains elusive.…”

Section: Inflammation-associated Depression – Human Studiesmentioning

confidence: 99%

Inflammation-associated depression: From serotonin to kynurenine

Dantzer

O’Connor

Lawson

et al. 2011

Psychoneuroendocrinology

646

481

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In the field of depression, inflammation-associated depression stands up as an exception since its causal factors are obvious and it is easy to mimic in an animal model. In addition, quasiexperimental studies can be carried out in patients who are treated chronically with recombinant cytokines for a medical condition since these patients can be studied longitudinally before, during and after stimulation of the immune system. These clinical studies have revealed that depression is a late phenomenon that develops over a background of early appearing sickness. Incorporation of this feature in animal models of inflammation-associated depression has allowed the demonstration that alterations of brain serotoninergic neurotransmission do not play a major role in the pathogenesis. This is in contrast to the activation of the tryptotphan degrading enzyme indoleamine 2,3 dioxygenase that generates potentially neurotoxic kynurenine metabolites such as 3-hydroxy kynurenine and quinolinic acid. Although the relative importance of peripherally versus centrally produced kynurenine and the cellular source of production of this compound remain to be determined, these findings provide new targets for the treatment of inflammation-associated depression that could be extended to other psychiatric conditions mediated by activation of neuroimmune mechanisms.

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Section: Inflammation-associated Depression – Human Studiesmentioning

confidence: 99%

Inflammation-associated depression: From serotonin to kynurenine

Dantzer

O’Connor

Lawson

et al. 2011

Psychoneuroendocrinology

646

481

View full text Add to dashboard Cite

show abstract

“…Also, many individuals with depression have elevated 24-h corticosteroid levels and escape dexamethasone-induced suppression of the HPA axis; normalization of these parameters generally precedes the relief of depressive symptoms, and the degree of HPA-axis normalization in turn predicts the relapse probability. Finally, anti-glucocorticoids given (as adjunct to antidepressants) to patients with psychotic depression accelerate and increase chances on successful treatment (DeBattista and Belanoff, 2006), provided that the anti-glucocorticoids levels are very high (Blasey et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Chronic stress effects on hippocampal structure and synaptic function: relevance for depression and normalization by anti-glucocorticoid treatment

Krugers

Lucassen

Karst

et al. 2010

Front.Syna.Neurosci.

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Exposure of an organism to environmental challenges activates two hormonal systems that help the organism to adapt. As part of this adaptational process, brain processes are changed such that appropriate behavioral strategies are selected that allow optimal performance at the short term, while relevant information is stored for the future. Over the past years it has become evident that chronic uncontrollable and unpredictable stress also exerts profound effects on structure and function of limbic neurons, but the impact of chronic stress is not a mere accumulation of repeated episodes of acute stress exposure. Dendritic trees are reduced in some regions but expanded in others, and cells are generally exposed to a higher calcium load upon depolarization. Synaptic strengthening is largely impaired. Neurotransmitter responses are also changed, e.g., responses to serotonin. We here discuss: (a) the main cellular effects after chronic stress with emphasis on the hippocampus, (b) how such effects could contribute to the development of psychopathology in genetically vulnerable individuals, and (c) their normalization by brief treatment with anti-glucocorticoids.

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“…Psychotic major depression was not significantly affected by antiglucocorticoid treatment. Although a study with mifepristone using plasma concentrations to assess drug exposure have been positive (Blasey et al, 2009), several studies with CRH R1 receptor antagonists as monotherapy have failed (Holtzheimer and Nemeroff, 2008).…”

Section: Monotherapy Targets Of the Hypothalamic Pituitary Axismentioning

confidence: 99%