The purpose of this study is to examine the role of hormones in psychotic depression. This study will also determine the effectiveness of an investigational medication called mifepristone for treating patients with psychotic depression.

Psychotic major depression (PMD) is a severe and often debilitating form of depression. Studies indicate that PMD patients have increased corticotropin circadian rhythms, increased overnight cortisol levels, and prefrontal cognitive deficits that may be caused by hormone interactions. This study will examine these interactions and determine their effects. This study will compare three separate groups of patients a) Patients diagnosed with depression. b) Healthy control subjects (no history of a psychiatric diagnosis). c) Patients diagnosed with psychotic major depression, bipolar disorder in a depressive phase, schizophrenia or schizoaffective disorder.

Patients with Depression and Healthy control subjects will undergo a 3 day study. They will be admitted to Stanford University Hospital and will undergo neuropsychological testing, neuroimaging, and blood draws to measure cognitive functioning, brain structure and function, and daily hormone cycles.

PMD, Bipolar and Schizophrenic Patients will undergo a 24 day study. They will be randomly assigned to receive either mifepristone or placebo for 8 days. Patients who initially receive mifepristone will complete the study after 24 days. Patients who initially receive placebo and remain symptomatic can enter an add on study and begin taking mifepristone on Day 24 and remain in the study until Day 46. This study involves neuropsychological testing, neuroimaging, and blood draws to measure cognitive functioning, brain structure and function, and daily hormone cycles.

Ages Eligible for Study:  18 Years   -   85 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria for Participants with Psychotic Depression:

• DSM-IV diagnosis of Depression with or without psychosis, Bipolar Disorder, Schizophrenia, Schizoaffective Disorder
• Stable psychopharmacological medications for at least 1 week prior to study start

Inclusion Criteria for Control Participants:

• In good general health

Exclusion Criteria:

• Electroconvulsive therapy (ECT) or substance abuse within the past 6 months
• Unstable cardiovascular disease, hypertension, or endocrine disorder
• Pregnancy or planning to become pregnant