In the proposed study we intend to focus on the long term effects of increased cortisol activity in depressed patients. The major aims of the research are: 1) to Confirm that patients with psychotic major depression (PMD) exhibit greater cognitive impairment as measured by neuropsychological testing than nonpsychotic major depressed (NPMD) patients at baseline and to test the hypothesis that cognitive impairment at baseline correlates with plasma and urinary measures of cortisol in both PMD and NPMD patients; 2) to test the hypothesis that in comparison to NPHD patients, PMD patients have poorer outcome on measures of functioning, but not necessarily on measures of symptoms, at 15 months after the index episode; 3) to test the hypothesis that baseline measures of plasma and urinary cortisol do not predict outcome on measures of symptoms and functioning in PMD and NPMD patients at 4, 9, and 15 months after the index episode; 4) to test the hypothesis that at each of the three follow-up time points (4, 9, and 15 months), higher cortisol levels are associated with poorer outcome on measures of functioning, independent of depressive symptoms; 5) to test the hypothesis that at 15 month follow-up, plasma and urinary measures of cortisol in depressed patients correlate with cognitive impairment; and, 6) to explore whether in healthy control subjects there exists a relationship among urinary and plasma measures of cortisol, neuropsychological testing scores, and measures of social and occupational functioning. Eighty-one patients with diagnoses of unipolar major depression (42 psychotic and 39 nonpsychotic will be evaluated at baseline on measured of symptoms, social and occupational functioning, neuropsychological tenting, and plasma/urinary cortisol. Psychopharmacologic treatment will then be given according to a standardized protocol. Patients will be reevaluated at 4, 9, and 15 months on the same measures as at baseline except for the neuropsychological testing which will be repeated only at 9 and 15 months. Further understanding of the relationship between cortisol and long-term functioning in depression should help clinicians and researchers make more knowledgeable decisions regarding pharmacologic and psychological treatments during the first 15 months after the index episode.
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