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.
Roiser
Jonathan P
JP
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
Blackwell
Andrew D
AD
Cools
Roshan
R
Clark
Luke
L
Rubinsztein
David C
DC
Robbins
Trevor W
TW
Sahakian
Barbara J
BJ
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