Reduced Prefrontal Gyrification in Carriers of the Dopamine D4 Receptor 7-Repeat Allele With Attention Deficit/Hyperactivity Disorder: A Preliminary Report

Conclusions: Prefrontal gyrification is reduced in children with ADHD who also carry the DRD4 7R allele, and it relates to critical functional skills in the executive domain in carriers of the risk allele. More broadly, these effects highlight the importance of considering precise neurodevelopmental mechanisms through which risk alleles influence cortical neurogenesis and migration.IntroductionAttention deficit/hyperactivity disorder (ADHD) is a heterogeneous neuropsychiatric disorder characterized by developmentally inappropriate symptoms of inattention, impulsivity, and hyperactivity. The disorder is thought to affect around 1–5% of children and is highly heritable, with multiple genes of small effect contributing to the clinical phenotype (1). Although a number of genome-wide association studies (GWAS) [e.g., Refs. (2, 3)] have failed to show genome-wide significance in ADHD, a recent GWAS meta-analysis found associations with ADHD for 12 independent genome-wide significant loci (4). The dopamine D4 receptor (DRD4) gene, expressed primarily in limbic regions and the prefrontal cortex (PFC) (5), contains a 48-base-pair variable number tandem repeat in exon 3. A 7-repeat (7R) allele has been identified as a prominent risk allele for ADHD (6–10) and produces a blunted response to dopamine (11). At a neurochemical level, an abnormality in dopaminergic neurotransmission is well established in ADHD (12, 13) in keeping with the therapeutic effects of methylphenidate (...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research

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