But the data doesn't say that.
The comission errors all fall within 1 SD of eachother regardless of ls or ss allele -- which means there is no difference.
The study authors used a SHITTY surrogate test and poorly correlated data to identify a possible association, (it's possible I'll get struck by lightning)
I think you've been continually overstating the importance of reaching 2 sigma when we are looking for ie genes that could have a small effect on risk, this isn't particle physics. For example, we might be looking for a gene that increases the risk of adverse effects occurrence in 1/10 people with the gene, and it might only have a small effect on that 1/10 person. Nobody is suggesting these neuropsychiatric disease related genes are deterministic, and after all, people with a short form 5-HTTLPR only have increased risk of MDD
after stress.
But I'm not sure if you even read the results section of the study that I posted, and bothered to look at the Beck depression inventory measures they took as well..
"Repeated-measures analysis of variance (ANOVA) was used to examine data from the Affective Go/No-Go test. There was a highly significant shift-by-genetic-subgroup interaction for commission errors in the Ecstasy users (F=6.81, df=2, 64, p<0.003) but not in the comparison subjects (F=0.16, df=2, 55, p=0.85).
In the
ll subgroup of the Ecstasy users, and in all genetic subgroups in the comparison group, commission errors declined as expected from shift to nonshift blocks.
However, the ls and ss subgroups of Ecstasy users did not make the expected reduction in errors from shift to nonshift blocks (
Figure 1).
~ The Ecstasy users scored significantly higher on the Beck Depression Inventory than comparison subjects within the
ss (Ecstasy group mean=11.8, SD=9.6; comparison group mean=3.9, SD=3.2) (z=2.4, p<0.02) and
ls (Ecstasy group mean=8.1, SD=5.5; comparison group mean=5.2, SD=5.6) (z=2.4, p<0.02) genotype subgroups, but the difference in the
ll subgroup was not significant (Ecstasy group mean=7.5, SD=6.0; comparison group mean=5.3, SD=3.1) (z=1.0, p=0.32).
Second, each individual was categorized as either not depressed or depressed on the basis of the accepted cutoff point of 9 on the Beck Depression Inventory. The proportions of individuals categorized as depressed or not depressed showed a strong tendency to differ in the Ecstasy users when classified by 5-HTTLPR genotype (χ
2=5.95, df=2, p<0.06)—there were more individuals categorized as depressed in the
ss subgroup of Ecstasy users. The proportions of depressed versus nondepressed individuals did not show this tendency to differ as a function of 5-HTTLPR genotype in the comparison group (χ
2=0.55, df=2, p=0.76)."
Furthermore the Go-NoGo test is highly biased
Does the Emotional Go/No-Go Task Really Measure Behavioral Inhibition? Convergence with Measures on a Non-Emotional Analog
It must be noted that any conclusions regarding the emotional go/no-go task drawn from the present results are limited by the lack of data on the current mood state of participants.
and
"
However, unexplored gender and mood effects on performance suggest that the emotional go/no-go task will continue to be more of a research tool than part of a standard clinical battery for the time being."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562664/
First off, if the MDMA users with a short form have a higher incidence of depression (they did score higher on the Beck inventory), then I don't know why you would discount the findings of a study showing that same group didn't have the normal reduction of commission errors from shift blocks to non-shift blocks (the same thing we see in normal volunteers after tryptophan depletion) in a study that is examining the effect of 5-HTTLPR on MDMA user's mood and function.
...But let me quote the abstract of the study you posted, because you seem to just be reading the provocative title and then misleading people about the actual content therein;
"This study tested the convergence of behavioral inhibition measures across emotional and non-emotional versions of the same go/no-go task in 85 college students. The two tasks differed only in the stimuli used for trial cues (i.e., circles versus facial expressions). Moderate correlations (
r = .51 to
r = .56) between commission errors across the emotional and non-emotional tasks support the construct validity of behavioral inhibition. Further, parametric manipulation of preceding context had comparable effects on performance on the two tasks.
Responses were slower and more variable, commission errors were more numerous, and perceptual sensitivity was lower on the emotional than the non-emotional task. A bias for happy faces on the emotional task resulted in faster responses and more commission errors for happy than sad faces despite marginally greater sensitivity for the latter
. These results suggest that the basic neuropsychological constructs of the original go/no-go task were preserved in the emotional adaptation."
(from Discussion) "These results support the use of the emotional go/no-go task to test the emotional biasing of behavioral inhibition."
Basically, If you are in a bad mood, bored, or otherwise not "happy" the test is absolute crap.
Here it was found that tryptophan depletion in healthy volunteers causes function on an affective go/no go test to be similar to that of MDMA users with a short form but there
weren't effects on mood
https://www.ncbi.nlm.nih.gov/pubmed/11351939 -
"A robust reduction in total tryptophan was achieved in the test group. Subjects receiving the placebo drink showed the expected effect of shift on the affective shifting task, that is, more errors in the more difficult shift versus the non-shift condition.
The tryptophan-depleted group made a similar number of errors in the shift trials but failed to reduce the number of errors in the non-shift trials. The tryptophan-depleted group showed a significant impairment on the delayed pattern recognition task. No significant effects on the subjective mood measures were found.
Tryptophan depletion abolished the normal tendency to improve error scores on non-shift trials in response to affective cues on a go/no-go task."
Mind you that only people with the short form show issues with mood after tryptophan depletion.
The test itself wouldn't be as useful if it wasn't somewhat sensitive to the neuropsychiatric status of the person. One example is that people with depression react faster to sad faces than happy faces. In that situation you aren't going to say "Well they rated themselves higher on a depression inventory so toss the results".
Or in this particular case, you aren't going to discount the mood of the person being tested because if the acute mood could be related to 5-HTTLPR's modulation of adverse effects of MDMA then that is relevant. So you're not going to 100% separate function and mood...
There are similarities between the performance of MDMA users with a short form and healthy volunteers after tryptophan depletion "TRP depletion increased response times for happy but not sad targets in an affective go/no-go task and
slowed responding in a visual discrimination and reversal learning task." -
https://www.ncbi.nlm.nih.gov/pubmed/12185399/
Such a test has also been combined with neuroimaging
https://www.ncbi.nlm.nih.gov/pubmed/12090812/
Overactive MAO-A would reduce the effects of serotonin releasers like MDMA.
I believe we've already discussed this topic but just a reminder; I'm not proposing that the adverse effects are due to an acute excess of serotonin, but rather a deficit of serotonergic signaling on the comedown... Which would be
worse in somebody with moreso functional MAO.
