This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothalamus-pituitary-adrenal (HPA) axis dysregulation has been observed in patients with mood disorders. Treatment with Mifepristone appears to reset HPA normal rhythm by blocking GR-II Cortisol receptors in the prefrontal cortex and other areas of the brain. Mifepristone has been studied at Stanford University since 1998 as a treatment for psychotic major depression (PMD). Analyses of cortisol and adrenal corticotropin hormone (ACTH) levels in patients receiving Mifepristone has shown that after Mifepristone treatment, the HPA axis appears to normalize. Neuropsyciatric tests of patients before and after receiving Mifepristone revealed that patients with psychotic depression had greater cognitive deficits compared to non-psychotically depressed patients (NPMD) and healthy control subjects. Greater clinical and cognitive improvement was seen in patients receiving Mifepristone compared to placebo. The primary objective of this study is to investigate the relationships among findings in structural and functional neuroimaging, cognitive testing, sleep and HPA axis dysregulation in psychotic depression and the durability of the effect and mechanism of action for Mifepristone in the treatment of psychotic depression.
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