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