Abstract
In order to better understand the underpinnings of attention-deficit/hyperactivity disorder (ADHD), we targeted the relationship of attentional, cognitive control and motivational processes with DNA methylation patterns of 60 candidate genes in boys at early school age. Participants (6 to 8 years; N = 82) were selected from a German longitudinal cohort (FRANCES). ADHD-related behaviour was assessed via maternal ratings. Performance and event-related potential measures (inter alia Cue-P3 and Nogo-P3), which were recorded in a motivational go/nogo task, indicated diminished attentional orienting, reduced inhibitory response control and a larger motivational effect on performance in ADHD already at this relatively young age. Methylation patterns were analysed in buccal cell DNA with the Illumina HumanMethylation 450K array. For CpG sites at genes of the dopaminergic (COMT, ANKK1) and the neurotrophic (BDNF, NGFR) system, associations with the Nogo-P3 as well as ADHD symptom severity were found suggesting that these systems are involved in response control deficits in ADHD. Methylation effects related to both functional aspects and ADHD behaviour were also observed for DPP10 and TPH2. Epigenetic mechanisms may play a role in ADHD-associated deficits but findings need to be replicated in larger samples and are limited by the fact that only peripheral methylation could be considered.
Highlights
As sample size was too small to expect methylome-wide statistical significance (p < 1e-7), we considered candidate genes thought to play a role in the aetiology of attention-deficit/hyperactivity disorder (ADHD) (e.g., ‘classic’ ADHD genes as dopaminergic and noradrenergic genes, genes encoding proteins involved in cell adhesion and migration) as reviewed by Banaschewski et al.[25] and genes found in the methylome-wide analysis of Wilmot et al.[24] for children in a comparable age range
In order to enhance our understanding of ADHD, we investigated attentional, cognitive control and motivational processes in boys at early school age and associations with DNA methylation variations
The following conclusions may be drawn from our study: 1. Diminished attentional orienting, reduced inhibitory response control and larger motivational performance effects appear to characterize boys with ADHD symptoms already at early school age
Summary
82 boys (aged 6 to 8 years) were included in the present investigation. They were selected from the FRANCES (Franconian Cognition and Emotion Studies) cohort. 215 children (113 boys) took part in the EEG lab session. Those boys/families (N = 91), who responded to an invitation letter (but were not actively contacted in a later phase of recruiting due to prenatal risk factors like alcohol exposure, prenatal depression or smoking), were included here to prevent an overrepresentation of prenatal risk factors and to achieve a more representative sample. Children did not use psychotropic medication except for four boys taking methylphenidate These four boys were at least drug-free for 24 hours before the assessments.
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