A long range objective of this study is to explore application of cortisol measures to disciminate among subtypes of depressive disorders, emphasizing relationship between elevated cortisol and dopamine activity as they may apply to the biology of delusion depression - a form of major depression with high morbidity and mortality. Key lines in this research are our observations that: a) dexamethasone increases plasma-free dopamine levels in man as well as dopamine concentrations in specific areas of rat brain; and b) psychotic depressives demonstrate significantly greater plasma cortisol and free dopamine levels (pre- and postdexamethasone) than do nonpsychotic depressed patients.
Specific Aims i nclude: 1) to test the hypothesis that unipolar depressed patients who demonstrate very high postdexamethsone cortisol levels (e.g., greater than or equal to 15 Mug/dl) have a significantly higher incidence of mood congruent psychosis than do unipolar patients with lower postdexamethasone cortisol levels; 2) to confirm our finding that a 1 mg. dose of dexamethasone significantly increases plasma free dopamine levels in both normal control subjects and some psychiatric patients; to test the hypothesis that dexamethasone-induced increases in plasma free dopamine levels are dose related; to determine if increases in plasma free dopamine are also accompanied by changes in plasma levels of conjugated dopamine and conjugated and unconjugated dopamine metabolites; 3) to test the hypotheses that pre- and postdexamethasone plasma free dopamine levels are elevated in some unipolar depressed patients; and within the unipolar group, dopamine levels are higher in those with delusions than in those without similar psychotic thinking; to determine if increases in dopamine levels are accompanied by increases in levels of other catecholamines; to confirm the observations that unipolar delusional patients demonstrate lower mean plasma dopamine-Beta-hydroxylase activity than do unipolar nondelusional patients or normal control subjects; 4) to confirm our preliminary observations that in unipolar depressed patients, nonsuppressed postdexamethasone cortisol values are distributed bimodally and to explore whether the two groups of nonsuppressors and the group of suppressors may be further discriminated clinically and biologically; 5) to further explore the relationships among platelet monoamine oxidase activity, plasma cortisol and catecholamine levels, and delusions in unipolar depressives.
