Sonuga-Barke, E. J. S., Kumsta, R., Schlotz, W., Lasky-Su, J., Marco, R., Miranda, A., Mulas, F., Oades, R. D., Banaschewski, T., Mueller, U. C., Andreou, P., Christiansen, H., Gabriels, I., Uebel, H., Kuntsi, J., Franke, B., Buitelaar, J. K., Ebstein, R. P., Gill, M., Anney, R. J. L., Roeyers, H., Rothenberger, A., Sergeant, J. A., Steinhausen, H-C., Asherson, P., & Faraone, S. V., (2011)
A Functional Variant of the Serotonin Transporter Gene (SLC6A4) Moderates Impulsive Choice in Attention Deficit/Hyperactivity Disorder Boys and Siblings. Biological Psychiatry, 70, 230-236. doi:10.1016/j.biopsych.2011.01.040 . [Request a copy] - View article

Introduction: Impulsive drive-for immediate reward (IDIR) & delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in ADHD. -- We hypothesized that IDIR would be associated with dopamine (DA) regulating genes and delay aversion with serotonin (5-HT) regulating genes.

Methods: IDIR and delay aversion were measured in 459 male children & adolescents (328 ADHD & 131 unaffected siblings) using a laboratory choice task. The sample was genotyped for the 5-HT transporter (5HTT / SLC6A4) promoter polymorphism & a DA (DAT1 / SLC6A3) 40-base pair VNTR (variable number tandem repeat) located in the 3`-untranslated region of the gene.

[Task: Participants were presented with a choice between small-sooner and large-delayed reward options in the context of a game-like space environment: There were 2 conditions - “no-post-reward delay condition,” where each trial followed on immediately after the participant had received their reward so that trial length was determined by the length of the pre-reward delay for the chosen option. In the “post-reward delay condition,” the trial length was equalized for the two reward options by including a period of post-reward delay (2 sec for the large-delayed option or 30 sec for the small-sooner option: Marco et al. 2009).]

Results:
1 - There was no effect of DAT1 on IDIR - and - no relationship for 5-HTTLPR on IDIR.

2 - As predicted 5-HTTLPR s-allele (short allele) carriers were more delay averse than non-carriers - there was no relationship for DAT1 .

3 - This effect was driven by the s/l (short/long) genotype in the ADHD group.

4 - These results were not altered by taking account of the rs25531 A/G SNP (polymorphism) and were independent of age, IQ and oppositional defiant disorder.

Background: The results support the genetic distinctiveness of IDIR & delay aversion in ADHD and implicate 5-HT function in delay aversion.

Possible explanations of the heterosis effect in the ADHD cases are presented.

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