Transient depressive relapse induced by catecholamine depletion: potential phenotypic vulnerability marker?
BACKGROUND
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 alpha-methylparatyrosine.


METHODS
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 alpha-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.


RESULTS
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).


CONCLUSIONS
Euthymic, medication-free subjects with a history of major depression demonstrate significant depressive symptoms when undergoing testing with alpha-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.
Berman
R M
RM
Connecticut Mental Health Center, Department of Psychiatry, Yale University School of Medicine, New Haven 06519, USA. robert.berman@yale.edu
Narasimhan
M
M
Miller
H L
HL
Anand
A
A
Cappiello
A
A
Oren
D A
DA
Heninger
G R
GR
Charney
D S
DS
D000328:Adult; D002395:Catecholamines / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D018592:Cross-Over Studies; D003866:Depressive Disorder / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005819:Genetic Markers; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012008:Recurrence; D012720:Severity of Illness Index; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D002395:Catecholamines; D004791:Enzyme Inhibitors; D005819:Genetic Markers; D008734:Methoxyhydroxyphenylglycol; D019805:alpha-Methyltyrosine; D006719:Homovanillic Acid