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Genetics of preparation and response control in ADHD : the role of DRD 4 and DAT 1
Author(s) -
Albrecht Björn,
Brandeis Daniel,
Sandersleben Henrik Uebel,
Valko Lilian,
Heinrich Hartmut,
Xu Xiaohui,
Drechsler Renate,
Heise Alexander,
Kuntsi Jonna,
Müller Ueli C.,
Asherson Philip,
Steinhausen HansChristoph,
Rothenberger Aribert,
Banaschewski Tobias
Publication year - 2014
Publication title -
journal of child psychology and psychiatry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.652
H-Index - 211
eISSN - 1469-7610
pISSN - 0021-9630
DOI - 10.1111/jcpp.12212
Subject(s) - impulsivity , psychology , endophenotype , dopamine , cognition , dopamine transporter , dopaminergic , neuroscience , developmental psychology , audiology , medicine
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 ( DRD 4) and dopamine transporter ( DAT 1) 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 DRD 4 7‐repeat allele and the DAT 1 10‐6 haplotype. Results Children with ADHD showed diminished performance and lower Cue‐P3, CNV and Nogo‐P3 amplitudes. Children with DRD 4 7R showed similar performance problems and lower Cue‐P3 and CNV , but Nogo‐P3 was not reduced. Children with the DAT 1 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 DRD 4 7R on performance and brain activity related to attentional orienting and response preparation, while DAT 1 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 DRD 4 and DAT 1 polymorphisms are functionally relevant risk factors for ADHD and presumably other disorders sharing these endophenotypes.