Transient depressive relapse induced by catecholamine depletion - Potential phenotypic vulnerability marker?

Background: Although state-related alterations in catecholamine function ha ve been well-described in depressed subjects, enduring abnormalities have b een less reliably identified. In our study, medication-free subjects with f ully remitted major depression underwent a paradigm of catecholamine deplet ion, via use of the tyrosine hydroxylase inhibitor alpha-methylparatyrosine . Method: Subjects underwent 2 sets of testing conditions in a double-blind, random-ordered, crossover design, approximately 1 week apart. They underwen t active catecholamine depletion (via oral administration of 5 g alpha-meth ylparatyrosine) or sedation-controlled, sham catecholamine depletion (via o ral administration of 250 mg diphenhydramine hydrochloride), during a 2-day observation, Serial mood ratings and blood samples were obtained, Results: Fourteen subjects completed the active testing condition; 13 compl eted sham testing. Subjects experienced marked, transient increases in core depressive and anxiety symptoms, as demonstrated by a mean 21-point increa se on Hamilton Depression Rating Scale scores. Furthermore, 10 (71%) of 14 subjects fulfilled relapse criteria during active testing, whereas 1 (8%) o f 13 subjects did so during sham testing. The severity of the depressive re action correlated with baseline plasma cortisol levels (r=0.59; P=.04). Conclusions: Euthymic, medication-free subjects with a history of major dep ression demonstrate significant depressive symptoms when undergoing testing with alpha-methylparatyrosine. This depressive reaction may represent a re liable marker for a history of depression. Further work is needed to clarif y the significance of this finding.