Tryptophan depletion and depressive vulnerability.
BACKGROUND
Rapid and transient depletion of tryptophan (TRP) causes a brief depressive relapse in most patients successfully treated with and taking selective serotonin reuptake inhibitors, but little change in drug-free, symptomatic depressed patients. This study investigates the effects of TRP depletion in drug-free subjects in clinical remission from a prior major depressive episode (MDE).


METHODS
Twelve subjects with a prior MDE, currently in clinical remission and drug-free for at least 3 months (patients), and 12 healthy subjects without personal or family history of Axis I disorder (controls), received TRP depletion. The study was conducted in a double-blind, controlled [full (102-g) and quarter-strength (25 g) 15-amino acid drinks], crossover fashion. Behavioral ratings and plasma TRP levels were obtained prior to, during, and after testing.


RESULTS
All subjects experienced significant depletion of plasma TRP on both test-drinks, showing a significant dose-response relation. Healthy control subjects had minimal mood changes, but patients had a depressive response of greater magnitude.


CONCLUSIONS
In the context of prior TRP depletion studies with antidepressant-treated, and drug-free symptomatic depressed patients, these results suggest that depression may be caused not by an abnormality of 5-HT function, but by dysfunction of other systems or brain regions modulated by 5-HT.
Moreno
F A
FA
Department of Psychiatry, College of Medicine, University of Arizona Health Science Center, Tucson 85724, USA.
Gelenberg
A J
AJ
Heninger
G R
GR
Potter
R L
RL
McKnight
K M
KM
Allen
J
J
Phillips
A P
AP
Delgado
P L
PL
D000328:Adult; D000368:Aged; D015415:Biomarkers; D018592:Cross-Over Studies; D003863:Depression / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012008:Recurrence; D012701:Serotonin / Q000097:blood*; D012727:Sex Characteristics; D014364:Tryptophan / Q000172:deficiency*
D015415:Biomarkers; D012701:Serotonin; D014364:Tryptophan