Monoamine depletion in unmedicated depressed subjects.
BACKGROUND
Although significant evidence suggests that diminished monoamine function is associated with clinical depression, catecholamine or indoleamine depletion alone has not been associated with significant mood changes in unmedicated depressed subjects or never-depressed control subjects. This study assesses the integrated role of these monoamine systems in depressed patients.


METHODS
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) catecholamine depletion. Ten subjects completed both conditions; two subjects were withdrawn after active testing and one after control testing.


RESULTS
Mean Hamilton Depression Rating Scale (HDRS) scores decreased progressively throughout the study days (baseline 26.7 points +/- 1.7 SEM and termination 20.0 +/- 2.4, active depletion; baseline 26.1 points +/- 2.3 SEM and termination 23.2 +/- 2.6, control testing) but did not differ between groups. Only three patients demonstrated 20% or greater increases from baseline HDRS at any point during the observation days.


CONCLUSIONS
Overall, results show 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.
Berman
Robert M
RM
Abraham Ribicoff Center Clinical Neuroscience Research Unit of the Connecticut Mental Health Center, New Haven, Connecticut, USA.
Sanacora
Gerard
G
Anand
Amit
A
Roach
Lisa M
LM
Fasula
Madonna K
MK
Finkelstein
Catherine O
CO
Wachen
R Mathew
RM
Oren
Dan A
DA
Heninger
George R
GR
Charney
Dennis S
DS
D000328:Adult; D002395:Catecholamines / Q000502:physiology*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D004155:Diphenhydramine; D004298:Dopamine / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000502:physiology; D010555:Personality Inventory; D012701:Serotonin / Q000502:physiology*; D014364:Tryptophan; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D012701:Serotonin; D019805:alpha-Methyltyrosine; D014364:Tryptophan; D004155:Diphenhydramine; D004298:Dopamine; D009638:Norepinephrine