Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity.
BACKGROUND
Reduced serotonin neurotransmission is implicated in disorders of impulse control, but the involvement of serotonin in inhibitory processes in healthy human subjects remains unclear.


OBJECTIVE
To investigate the effects of an acute manipulation of serotonin and genotype at a functional polymorphism in a gene coding for the serotonin transporter (5-HTT) on an established measure of response inhibition.


METHODS
Serotonin function was reduced by the acute tryptophan depletion (ATD) procedure in a double-blind, crossover design in 42 healthy subjects. The Stop Signal Task (SST) was administered 5-7 h after drink administration. The influences of 5-HTT polymorphism, gender and trait impulsivity were investigated.


RESULTS
ATD was associated with significant depletion of plasma tryptophan levels but did not increase the stop signal reaction time in comparison to the balanced (placebo) amino acid mixture. Subjects possessing the short allele of the 5-HTT polymorphism were not more impulsive on the SST than subjects homozygous for the long allele under placebo conditions and were not disproportionately sensitive to the effects of ATD. There was no effect of gender or trait impulsivity on ATD-induced change.


CONCLUSIONS
We find no support for the involvement of brain serotonin neurotransmission in this form of inhibitory control in healthy human subjects.
Clark
L
L
Department of Experimental Psychology, University of Cambridge, Downing Street, and Department of Medical Genetics, Addenbrooke's Hospital, Cambridge, UK. lc260@cam.ac.uk
Roiser
J P
JP
Cools
R
R
Rubinsztein
D C
DC
Sahakian
B J
BJ
Robbins
T W
TW
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D018592:Cross-Over Studies; D018753:Diet, Protein-Restricted / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007266:Inhibition, Psychological; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D011930:Reaction Time; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014364:Tryptophan / Q000172:deficiency* / Q000502:physiology
D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014364:Tryptophan