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A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings

(2011) BIOLOGICAL PSYCHIATRY. 70(3). p.230-236
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Abstract
Background: Impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in attention-deficit/hyperactivity disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion would be associated with serotonin-regulating genes. Methods: Impulsive drive for immediate reward and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) with a laboratory choice task. The sample was genotyped for the 5HTT (SLC6A4) promoter serotonin-transporter-linked polymorphic region polymorphism and a DAT1 (SLC6A3) 40-base pair variable number tandem repeat located in the 3'-untranslated region of the gene. Results: There was no effect of dopamine transporter (DAT)1 on IDIR. As predicted, serotonin-transporter-linked polymorphic region s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G single nucleotide polymorphism and were independent of age, IQ, and oppositional defiant disorder symptoms. Conclusions: The results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presented.
Keywords
COMBINED-TYPE ADHD, REACTION-TIME PERFORMANCE, DEFICIT HYPERACTIVITY DISORDER, ASSOCIATION, POLYMORPHISM, CHILDREN, 5-HTTLPR (SLC6A4), attention-deficit/hyperactivity disorder, DAT1 (SLC6A3), delay aversion, impulsivity, DELAY AVERSION, TRYPTOPHAN DEPLETION, CRITERION VALIDITY, DOPAMINE

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Citation

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Chicago
Barke, Edmund, Robert Kumsta, Wolff Schlotz, Jessica Lasky-Su, Rafaela Marco, Ana Miranda, Fernando Mulas, et al. 2011. “A Functional Variant of the Serotonin Transporter Gene (SLC6A4) Moderates Impulsive Choice in Attention-deficit/hyperactivity Disorder Boys and Siblings.” Biological Psychiatry 70 (3): 230–236.
APA
Barke, E., Kumsta, R., Schlotz, W., Lasky-Su, J., Marco, R., Miranda, A., Mulas, F., et al. (2011). A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings. BIOLOGICAL PSYCHIATRY, 70(3), 230–236.
Vancouver
1.
Barke E, Kumsta R, Schlotz W, Lasky-Su J, Marco R, Miranda A, et al. A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings. BIOLOGICAL PSYCHIATRY. 2011;70(3):230–6.
MLA
Barke, Edmund et al. “A Functional Variant of the Serotonin Transporter Gene (SLC6A4) Moderates Impulsive Choice in Attention-deficit/hyperactivity Disorder Boys and Siblings.” BIOLOGICAL PSYCHIATRY 70.3 (2011): 230–236. Print.
@article{2109085,
  abstract     = {Background: Impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in attention-deficit/hyperactivity disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion would be associated with serotonin-regulating genes. Methods: Impulsive drive for immediate reward and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) with a laboratory choice task. The sample was genotyped for the 5HTT (SLC6A4) promoter serotonin-transporter-linked polymorphic region polymorphism and a DAT1 (SLC6A3) 40-base pair variable number tandem repeat located in the 3'-untranslated region of the gene. Results: There was no effect of dopamine transporter (DAT)1 on IDIR. As predicted, serotonin-transporter-linked polymorphic region s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G single nucleotide polymorphism and were independent of age, IQ, and oppositional defiant disorder symptoms. Conclusions: The results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presented.},
  author       = {Barke, Edmund and Kumsta, Robert and Schlotz, Wolff and Lasky-Su, Jessica and Marco, Rafaela and Miranda, Ana and Mulas, Fernando and Oades, Robert D and Banaschewski, Tobias and Mueller, Ueli and Andreou, Penny and Christiansen, Hanna and Gabriels, Isabel and Uebel, Henrik and Kuntsi, Jonna and Franke, Barbara and Buitelaar, Jan and Ebstein, Richard and Gill, Michael and Anney, Richard and Roeyers, Herbert and Rothenberger, Aribert and Sergeant, Joseph and Steinhausen, Hans Christoph and Asherson, Philip and Faraone, Stephen V},
  issn         = {0006-3223},
  journal      = {BIOLOGICAL PSYCHIATRY},
  keywords     = {COMBINED-TYPE ADHD,REACTION-TIME PERFORMANCE,DEFICIT HYPERACTIVITY DISORDER,ASSOCIATION,POLYMORPHISM,CHILDREN,5-HTTLPR (SLC6A4),attention-deficit/hyperactivity disorder,DAT1 (SLC6A3),delay aversion,impulsivity,DELAY AVERSION,TRYPTOPHAN DEPLETION,CRITERION VALIDITY,DOPAMINE},
  language     = {eng},
  number       = {3},
  pages        = {230--236},
  title        = {A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings},
  url          = {http://dx.doi.org/10.1016/j.biopsych.2011.01.040},
  volume       = {70},
  year         = {2011},
}

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