Comments on Roiser et al (2004)
Reference:
Roiser JP, Cook LJ, Cooper JD, Rubinsztein DC, Sahakian BJ. (2005) Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional processing in ecstasy users. Am J Psychiatry 162(3):609-612.
Ilsa Jerome PhD, March, 2005
Recently Roiser and colleagues published a paper in the most recent issue of the American Journal of Psychiatry titled “Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional processing in ecstasy users.” The researchers found that in ecstasy users, having at least one “short” (s) form of the serotonin transporter gene was associated with higher scores on a measure of depression symptoms and less sensitivity to changes in rules on a Go/No Go, while having at least one s form of the serotonin transporter gene did not affect depression scores or task performance in non-ecstasy users. The results present a strong case for increased vulnerability to mild depression after repeated ecstasy use in people with specific types of serotonin transporter gene. However, these findings do not match the general tenor of research in ecstasy users, which at present have not found a unique link between ecstasy use and increased psychological problems, instead finding a link between substance use in general and psychological problems. As is true of all studies, this study comes with limitations, including retrospective design and alternate understanding of one measure used in the study. If the findings are replicated, they might suggest that using ecstasy on 30 or more occasions could increase likelihood of depression, but do not suggest that moderate ecstasy use should have similar effects.
Roiser and colleagues studied the effects of serotonin transporter genotype and ecstasy use on depression symptoms in 66 ecstasy users (48 men, 18 women), 30 cannabis users (15 men, 15 women) and 28 non-drug users (15 men, 13 women). In order to be in the study, all ecstasy users had to have taken ecstasy on at least 30 occasions and to have abstained from it for at least three weeks prior to testing. The researchers do not provide lifetime ecstasy consumption figures in this paper, but a previous report by the same researchers listed lifetime consumption of about 273 occasions for current users and 796 for former users. The researchers measured depression with the Beck Depression Inventory (BDI), a self-report measure, and with an emotion-word Go/No Go task. The Go/No Go task requires people to respond on seeing targets and to refrain from responding on seeing non-targets. In this case, the targets were either happy or sad words, and the type of target (happy or sad) was switched several times during the test. People who are not depressed respond more quickly to happy words, and peopel who are depressed respond more quickly to sad words. Roiser and colleagues also assessed impulsivity with another self-report questionnaire, the Impulsiveness, Venturesomeness and Empathy questionnaire (IVE) and gathered information on drug use histories with another questionnaire.
The serotonin transporter gene comes in two common forms, long (or “L”) and short (or “s”), with the short form associated with psychological problems in people experiencing life stress. People can possess one of three combinations of serotonin transporter gene; LL, Ls, or ss. (The paper used lowercase “l” to refer to the long form of the gene, but for clarity, I have capitalized the L to distinguish it from the number 1 or a capital I.)
Roiser and colleagues found that 21 of 66 ecstasy users had the LL genotype, 31 had the Ls, and 15 had the ss genotype. 21 of 58 cannabis and non-drug users had the LL genotype, 26 had the Ls genotype and 11 had the ss genotype. The researchers failed to detect any significant differences between serotonin transporter genotypes in non-ecstasy users and ecstasy users. Analyzing BDI scores within each group, the authors found that for ecstasy users, having two copies of the “s” form of the serotonin transporter gene (the “ss genotype) were associated with BDI scores higher than 9, whereas the ss genotype was not associated with higher BDI scores in non-ecstasy users. Roiser and colleagues did not report response times to happy versus sad words, so it is not clear whether any group or genotype gave responses that were similar to depressed people. However, Roiser and colleagues also compared the number of errors made on trials where the type of target had just been switched (for instance, from happy words to sad words) with trials where the target remained the same as the previous target. In most cases, people make more errors on “switch” trials than on non-switch trials, and this is what happened for non-ecstasy users of all genotypes, and in ecstasy users with the LL genotype. However, error rates on switch and non-switch trials did not differ in ecstasy users with Ls or ss genotypes. The researchers performed analysis that controlled for use of other drugs on Go/No Go error rates in ecstasy users, and failed to find effects from other drugs. Lastly, they found that while ecstasy users had higher impulsivity scores than cannabis users or non-drug users, amphetamine use was associated with higher impulsivity, and when the researchers controlled for amphetamine use, ecstasy use was no longer associated with higher impulsivity.
This study suggests that genetic differences might account for differences in long-term effects of repeated ecstasy use, with the short form of the serotonin transporter gene making people more at risk of depression symptoms. Like most studies in this area, this study is retrospective, so it is possible that people with the ss genotype who already had high depression symptoms might also be more likely to take ecstasy. A study in a representative sample has already suggested that psychological problems are more likely to appear before ecstasy use than afterwards (Lieb et al. 2002) and another study in ecstasy users and controls suggests that ecstasy users are more likely to report childhood abuse than non-users (Singer et al.2004). It is also interesting that no information is reported on response times for happy and sad words, raising the possibility that the groups did not differ on response times, despite differences in BDI depression scores.
Roiser et al’s results differ from those in other studies in several ways. Many recent studies have detected higher depression scores in ecstasy users, and some in polydrug users or cannabis users as well (for instance, see Dafters et al. 2004; Daumann et al. 2004; Milani et al. 2004). Furthermore, several studies, including a longitudinal one, found that continued cannabis use was more strongly associated with psychological problems, including depression, than continued ecstasy use (Daumann et al. 2004). Given these results, it is surprising both that Roiser and colleagues failed to find overall differences in BDI scores in ecstasy and cannabis users. These findings suggest that, at the least, more than one factor may be involved in increasing depression symptoms in substance users. Alternately, error rates in switch versus non-switch trials strongly resembles measures of executive function. Previous studies have detected lower executive function scores in at least some groups of ecstasy users (Alting von Geusau et al. 2004; Gouzoulis-Mayfrank et al. 2000; Halpern et al. 2004). so it is possible that the lack in switch versus non-switch error rates is better interpreted as relating to executive function. Lastly, it should be noted that at least one study has found that even people who think they are only taking MDMA are unintentionally exposed to MDA and amphetamines (Kalasinsky et al. 2004).
If future studies continue to find the results described above, then it is possible that ecstasy use increases the likelihood of experiencing depression symptoms in people without the long form of the serotonin transporter gene. However, these findings do not suggest that moderate ecstasy use, let alone one or two doses of MDMA, are associated with increased depression symptoms.
Reference:
Roiser JP, Cook LJ, Cooper JD, Rubinsztein DC, Sahakian BJ. (2005) Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional processing in ecstasy users. Am J Psychiatry 162(3):609-612.
View Roiser et al. 2005 (PDF)
