The effect of acute tryptophan depletion and fenfluramine on quantitative EEG and mood in healthy male subjects.
BACKGROUND
Efforts to model putative serotonergic deficits associated with affective disorders have frequently involved acute tryptophan depletion (ATD) as a manipulation strategy aimed at lowering brain serotonin synthesis. In an attempt to widen the scope of the measurement probes used in these investigations, the central actions of ATD and a subsequent dose of fenfluramine were examined via utilization of quantitative electroencephalography (EEG) and mood ratings.


METHODS
Electroencephalograms (EEG) and subjective mood ratings were assessed in 28 healthy men before and after double-blind ingestion of a tryptophan-depleting (T-) amino acid mixture, or a nutritionally balanced (B) amino acid mixture containing tryptophan, and again after a single-blind oral dose of D,L-fenfluramine hydrochloride (60 mg).


RESULTS
Compared to the B mixture, the T- mixture reduced total plasma tryptophan by more than 75% 5 hours after ingestion. Tryptophan depletion was associated with a modest lowering of mood and a slowing of EEG as indicated by increases in delta amplitude. Fenfluramine caused no change in mood but increased fast wave (beta) activity in anterior recordings when administered after the T-, but not after the B mixture.


CONCLUSIONS
Quantitative EEG measurements may be a promising method for studying the central mechanisms underlying serotonin-mediated changes in mood and behavior.
Department of Psychiatry, University of Ottawa, Ontario, Canada.
V J
VJ
Knott
A L
AL
Howson
M
M
Perugini
A V
AV
Ravindran
S N
SN
Young
D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects*; D000596:Amino Acids / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000175:diagnosis; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005277:Fenfluramine / Q000009:adverse effects*; D006304:Health Status; D006801:Humans; D008297:Male; D010865:Pilot Projects; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*
D000596:Amino Acids; D005277:Fenfluramine; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan