Roiser Jonathan P, Rogers Robert D, Cook Lynnette J, Sahakian Barbara J
Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Box 189, Hills Road, Cambridge, CB2 2QQ, UK.
Psychopharmacology (Berl). 2006 Oct;188(2):213-27. doi: 10.1007/s00213-006-0495-z. Epub 2006 Aug 29.
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.
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.
We assessed memory, decision-making, and executive function in ecstasy users and controls, stratifying by genotype at the 5-HTTLPR.
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.
The results are consistent with the hypothesis that cognitive impairment in ecstasy users may depend on genetic variation at the 5-HTTLPR.
3,4-亚甲基二氧甲基苯丙胺（摇头丸或“迷魂药”）是一种常见的滥用药物，已知会导致血清素（5-羟色胺）系统耗竭。许多研究报告称，摇头丸使用者在各种认知功能测量指标上与对照组存在差异。然而，文献报道并不一致，也有许多负面研究结果。这种不一致的一个原因可能是由于遗传和环境等多种因素导致个体对摇头丸有害影响的易感性存在差异。
研究5-羟色胺转运体基因连锁多态性区域（5-HTTLPR）的s等位基因携带者相对于l等位基因与血清素能神经传递减少相关，是否最易受摇头丸对认知功能影响这一假设。
我们对摇头丸使用者和对照组的记忆、决策和执行功能进行评估，并根据5-HTTLPR的基因型进行分层。
我们观察到，在摇头丸使用者和对照组中，5-HTTLPR基因型组在多项测量指标上存在差异。在执行风险决策任务时，ss和ls基因型的对照组比ll基因型的对照组更关注所选赌博获胜概率的差异。然而，在ss基因型的摇头丸使用者中，这种差异显著减弱。此外，与是否使用摇头丸无关，ss基因型的志愿者在视觉规划任务上的表现优于ll基因型的志愿者。
这些结果与摇头丸使用者的认知障碍可能取决于5-HTTLPR基因变异这一假设一致。
