268. Simultaneous catecholamine and indoleamine depletion in unmedicated depressed subjects

Abstract

Although significant evidence suggests that alterations in monoamine systems are associated with clinical depression, catecholamine or indoleamine depletion alone has not been associated with significant mood changes in unmedicated depressed subjects, a finding that complicates the classic monoamine hypotheses on the neurobiology of depression. As one possible explanation, dysfunction in one monamine system may be balanced by intact function in another. To test this hypothesis, unmedicated depressed subjects underwent a 2-week, double-blind, random-ordered crossover study consisting of the following active and control conditions respectively: indoleamine (via tryptophan depletion) plus catecholamine (via alpha-methyl-paratyrosine administration) depletion and, separately, indoleamine plus sham (via diphenhydramine administration) depletion and, separately, indoleamine plus sham (via diphenhydramine administration) catecholamine depletion. Ten subjects completed both conditions; 2 subjects were withdrawn after active testing and one after control testing. Time (F 7.1, df 4, 36, p = 0.0003) but not time-by-condition or condition effects were statistically significant. Mean HDRS scores decreased progressively throughout the study days (baseline 26.7 points ± 1.4 SEM; termination 21.3 ± 1.7). Response (i.e., >50% HDRS decrease and maximum score <15 points) rates were 3 [25%] of 12 subjects undergoing active testing and 4 [36%] of 11 undergoing control testing, inclusive of follow-up day ratings. Overall, results suggest that simultaneous disruptions of indoleamine and catecholamine function do not exacerbate symptoms in unmedicated depressed subjects, thus lending further support to the notion that monoamines regulate mood in actively depressed patients via indirect mechanisms.