Serotonin transporter polymorphism mediates vulnerability to loss of incentive motivation following acute tryptophan depletion.
The serotonin (5-HT) system is implicated in incentive motivational processes. The present study utilized the acute tryptophan depletion (ATD) procedure to investigate the effect of temporarily lowering 5-HT synthesis on motivation in healthy volunteers, stratifying the results by allelic variation at the serotonin transporter gene (5-HTTLPR). ATD resulted in a robust reduction in plasma tryptophan concentration. Consistent with a previous study, ATD attenuated motivationally speeded action on the Cued-Reinforcement Reaction Time task. The present investigation revealed that this effect was restricted to volunteers of the ss genotype, whereas ll volunteers exhibited intact motivationally speeded action following ATD (treatment x reinforcement probability x genotype interaction: F1,26=5.8, p=0.024). Furthermore, tryptophan availability to the brain was correlated positively with motivationally speeded action following ATD in the ss genotype group (rho13=0.71, p=0.006), whereas this correlation was negative in the ll genotype group (rho14=-0.60, p=0.023). This is the first study to suggest that allelic variation at the 5-HTTLPR mediates motivational responses to ATD in healthy volunteers. These data indicate that the s allele at the 5-HTTLPR may confer risk for depression via its effect on incentive motivational processing, and highlight the importance of genetic variation in determining individual responses to pharmacological treatments.
Department of Psychiatry, Addenbrooke's Hospital, Cambridge, UK, and Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA. j.roiser@ion.ucl.ac.uk
Jonathan P
JP
Roiser
Andrew D
AD
Blackwell
Roshan
R
Cools
Luke
L
Clark
David C
DC
Rubinsztein
Trevor W
TW
Robbins
Barbara J
BJ
Sahakian
D000328:Adult; D000704:Analysis of Variance; D003463:Cues; D018753:Diet, Protein-Restricted / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009042:Motivation; D011110:Polymorphism, Genetic; D011336:Probability; D011930:Reaction Time / Q000502:physiology; D012054:Reinforcement, Psychology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013223:Statistics as Topic; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*
D050486:Serotonin Plasma Membrane Transport Proteins; D014364:Tryptophan