DRD4 genotyping may differentiate symptoms of attention-deficit/hyperactivity disorder and sluggish cognitive tempo

Abstract

Objective: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3′-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor ( DRD4 ) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). Methods: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. Results: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. Conclusion: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.

Attention-deficit/hyperactive disorder updates

“…SNPs in DRD 4 relate to distinct domains of ADHD severity ( Cervantes-Henríquez et al, 2022 ). The 7R allele of the DRD4 gene is more prevalent in sluggish cognitive cases than in ADHD cases ( Bolat et al, 2020 ). It has been reported that the interaction between the methylation of CpG sites of DRD4 (CpG26 and CpG28) and phthalate metabolite levels can affect the attention level in ADHD patients ( Kim et al, 2021 ).…”

ADGRL3, FGF1 and DRD4: Linkage and Association with Working Memory and Perceptual Organization Candidate Endophenotypes in ADHD

“…ADHD etiology is complex and strongly related to neurotransmitter pathways, i.e., dopamine [42]. Family-based and genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the DRD4 gene associated with ADHD [43,[79][80][81][82][83][84][85]. Furthermore, genetic variants in the FGF1 [17,52] and ADGRL3 (LPHN3) [17,52,58,59,83,[86][87][88][89][90][91][92][93] genes are associated with ADHD and ADHD endophenotypes.…”

ADHD: Reviewing the Causes and Evaluating Solutions

“…For example, an analysis of both patients and the literature found an association of the 10-repeat/10-repeat genotype with ADHD only in adolescents [ 85 ], studies performed in children reported an association between the 10-repeat/10-repeat genotype and ADHD [ 86 , 87 ], while a recently published meta-analysis reported an association of the 10-repeat allele with ADHD in children and adolescents, specifically in European population [ 88 ]. However, there are also reports indicating no association at all between ADHD and the VNTR of DAT gene (9-repeat/10-repeat, 10-repeat/10-repeat, and 10-repeat/11-repeat genotypes) [ 89 ], no association between the 10-repeat/10-repeat allele with ADHD [ 90 ], and no association between ADHD and the 9-repeat or the 10-repeat alleles for this polymorphism [ 91 ]. The last three studies were performed in children.…”