The effect of polymorphism at the serotonin transporter gene on decision-making, memory and executive function in ecstasy users and controls.
BACKGROUND
3, 4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a popular drug of abuse known to result in depletions of the serotonin (5-HT) system. A number of studies have reported that ecstasy users differ from controls on a variety of measures of cognitive function. However, the literature is not consistent and many negative findings were also reported. One reason for such inconsistency might be interindividual variance in vulnerability to the deleterious effects of ecstasy due to a number of factors, both genetic and environmental.


OBJECTIVE
To investigate the hypothesis that carriers of the s allele at the 5-HT transporter gene-linked polymorphic region (5-HTTLPR), which was associated with reduced serotonergic neurotransmission relative to the l allele, would be most vulnerable to the effects of ecstasy on cognitive function.


METHODS
We assessed memory, decision-making, and executive function in ecstasy users and controls, stratifying by genotype at the 5-HTTLPR.


RESULTS
We observed that the 5-HTTLPR genotype groups differed on a number of measures in both the ecstasy users and the controls. While performing a risky decision-making task, ss and ls controls attended to differences in the probability of winning chosen gambles to a greater extent than the ll controls. However, this difference was dramatically attenuated in the ss ecstasy users. Furthermore, independent of ecstasy use, volunteers of the ss genotype outperformed the ll genotype on a visual planning task.


CONCLUSIONS
The results are consistent with the hypothesis that cognitive impairment in ecstasy users may depend on genetic variation at the 5-HTTLPR.
Roiser
Jonathan P
JP
Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Box 189, Hills Road, Cambridge, CB2 2QQ, UK.
Rogers
Robert D
RD
Cook
Lynnette J
LJ
Sahakian
Barbara J
BJ
D016022:Case-Control Studies; D003071:Cognition / Q000187:drug effects*; D003657:Decision Making / Q000187:drug effects*; D006801:Humans; D008568:Memory / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D019966:Substance-Related Disorders / Q000235:genetics* / Q000503:physiopathology
D050486:Serotonin Plasma Membrane Transport Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine