Genetics of preparation and response control in ADHD: The role of DRD4 and DAT1

Björn Albrecht; Daniel Brandeis; Henrik Uebel- von Sandersleben; Lilian Valko; Hartmut Heinrich; Xiaohui Xu; Renate Drechsler; Alexander Heise; Jonna Kuntsi; Ueli C Müller; Philip Asherson; Hans-Christoph Steinhausen; Aribert Rothenberger; Tobias Banaschewski

doi:10.1111/jcpp.12212

Genetics of preparation and response control in ADHD: The role of DRD4 and DAT1

Björn Albrecht, Daniel Brandeis, Henrik Uebel- von Sandersleben, Lilian Valko, Hartmut Heinrich, Xiaohui Xu, Renate Drechsler, Alexander Heise, Jonna Kuntsi, Ueli C Müller, Philip Asherson, Hans-Christoph Steinhausen, Aribert Rothenberger, Tobias Banaschewski

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

35 Citationer (Scopus)

Abstract

BACKGROUND: Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children.

METHODS: Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype.

RESULTS: Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions.

CONCLUSIONS: This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.

Originalsprog	Engelsk
Tidsskrift	Journal of Child Psychology & Psychiatry
Vol/bind	55
Udgave nummer	8
Sider (fra-til)	914-923
ISSN	0021-9630
DOI	https://doi.org/10.1111/jcpp.12212
Status	Udgivet - 13 feb. 2014

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10.1111/jcpp.12212

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Albrecht, B., Brandeis, D., von Sandersleben, H. U., Valko, L., Heinrich, H., Xu, X., Drechsler, R., Heise, A., Kuntsi, J., Müller, U. C., Asherson, P., Steinhausen, H-C., Rothenberger, A., & Banaschewski, T. (2014). Genetics of preparation and response control in ADHD: The role of DRD4 and DAT1. Journal of Child Psychology & Psychiatry, 55(8), 914-923. https://doi.org/10.1111/jcpp.12212

@article{e99707bf7be84c7f82c13d65ee9a7523,

title = "Genetics of preparation and response control in ADHD: The role of DRD4 and DAT1",

abstract = "BACKGROUND: Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children.METHODS: Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype.RESULTS: Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions.CONCLUSIONS: This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.",

author = "Bj{\"o}rn Albrecht and Daniel Brandeis and {von Sandersleben}, {Henrik Uebel-} and Lilian Valko and Hartmut Heinrich and Xiaohui Xu and Renate Drechsler and Alexander Heise and Jonna Kuntsi and M{\"u}ller, {Ueli C} and Philip Asherson and Hans-Christoph Steinhausen and Aribert Rothenberger and Tobias Banaschewski",

note = "{\textcopyright} 2014 The Authors. Journal of Child Psychology and Psychiatry. {\textcopyright} 2014 Association for Child and Adolescent Mental Health.",

year = "2014",

month = feb,

day = "13",

doi = "10.1111/jcpp.12212",

language = "English",

volume = "55",

pages = "914--923",

journal = "Journal of Child Psychology & Psychiatry",

issn = "0021-9630",

publisher = "Wiley-Blackwell",

number = "8",

}

Albrecht, B, Brandeis, D, von Sandersleben, HU, Valko, L, Heinrich, H, Xu, X, Drechsler, R, Heise, A, Kuntsi, J, Müller, UC, Asherson, P, Steinhausen, H-C, Rothenberger, A & Banaschewski, T 2014, 'Genetics of preparation and response control in ADHD: The role of DRD4 and DAT1', Journal of Child Psychology & Psychiatry, bind 55, nr. 8, s. 914-923. https://doi.org/10.1111/jcpp.12212

TY - JOUR

T1 - Genetics of preparation and response control in ADHD

T2 - The role of DRD4 and DAT1

AU - Albrecht, Björn

AU - Brandeis, Daniel

AU - von Sandersleben, Henrik Uebel-

AU - Valko, Lilian

AU - Heinrich, Hartmut

AU - Xu, Xiaohui

AU - Drechsler, Renate

AU - Heise, Alexander

AU - Kuntsi, Jonna

AU - Müller, Ueli C

AU - Asherson, Philip

AU - Steinhausen, Hans-Christoph

AU - Rothenberger, Aribert

AU - Banaschewski, Tobias

PY - 2014/2/13

Y1 - 2014/2/13

N2 - BACKGROUND: Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children.METHODS: Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype.RESULTS: Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions.CONCLUSIONS: This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.

AB - BACKGROUND: Difficulties with performance and brain activity related to attentional orienting (Cue-P3), cognitive or response preparation (Cue-CNV) and inhibitory response control (Nogo-P3) during tasks tapping executive functions are familial in ADHD and may represent endophenotypes. The aim of this study was to clarify the impact of dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) gene polymorphisms on these processes in ADHD and control children.METHODS: Behavioural and electrophysiological parameters from cued continuous performance tests with low and high attentional load were assessed in boys with ADHD combined type (N = 94) and controls without family history of ADHD (N = 31). Both groups were split for the presence of at least one DRD4 7-repeat allele and the DAT1 10-6 haplotype.RESULTS: Children with ADHD showed diminished performance and lower Cue-P3, CNV and Nogo-P3 amplitudes. Children with DRD4 7R showed similar performance problems and lower Cue-P3 and CNV, but Nogo-P3 was not reduced. Children with the DAT1 10-6 haplotype had no difficulties with performance or Cue-P3 and CNV, but contrary to expectations increased Nogo-P3. There were no Genotype by ADHD interactions.CONCLUSIONS: This study detected specific effects of DRD4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT1 10-6 was associated with elevated brain activity related to inhibitory response control, which potentially compensates increased impulsivity. As these genotype effects were additive to the impact of ADHD, the current results indicate that DRD4 and DAT1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.

U2 - 10.1111/jcpp.12212

DO - 10.1111/jcpp.12212

M3 - Journal article

C2 - 24521003

SN - 0021-9630

VL - 55

SP - 914

EP - 923

JO - Journal of Child Psychology & Psychiatry

JF - Journal of Child Psychology & Psychiatry

IS - 8

ER -

Genetics of preparation and response control in ADHD: The role of DRD4 and DAT1

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