Gene polymorphisms of the dopamine D4 receptor (DRD4) and serotonin transporter (5-HTT) are under discussion as potential genetic risk factors for hyperkinetic disorder (HD).
This endorses the general thesis that DRD4 exon 3 VNTR polymorphism is related to ADHD, despite that the exact length or number of repeats of the associated alleles varies across ethnicity.
Meta-analyses of pooled ORs support association of schizophrenia to the Ser311Cys polymorphism in DRD2 and the T102C polymorphism in HTR2A, and of attention deficit hyperactivity disorder to the 48-bp repeat in DRD4.
An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit/hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators.
Schizophrenia and Attention Deficit Hyperactivity Disorder, which lead to failure of attentional modulation and working memory, introduce significant changes in gamma responses and have significant associations with genetic polymorphisms of dopamine receptor D4 (DRD4), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT).
The present findings indicate that the interaction between methylation of CpG7 of DRD4 and prenatal maternal stress may be predictive of the treatment response to MPH in youth with ADHD.
Schizophrenia and Attention Deficit Hyperactivity Disorder, which lead to failure of attentional modulation and working memory, introduce significant changes in gamma responses and have significant associations with genetic polymorphisms of dopamine receptor D4 (DRD4), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT).
In recent years a large number of studies on different candidate genes for ADHD have been published, most have focused on genes involved in the dopaminergic neurotransmission system, such as DRD4, DRD5, DAT1/SLC6A3, DBH, DDC.
We drew comparisons with a single nucleotide polymorphism in the dopamine D1 receptor (DRD1) gene, which was associated with ADHD within our cohort, and a polymorphism within the dopamine transporter (DAT1) gene, reported to have additive effects with the DRD4 7-repeat allele.
SNPs in seven genes including SLC1A3, SLC6A3, HTR4, ADRA1A, HTR2A, SNAP25, and COMT showed a nominal level of association with ADHD (P values <0.05), but none remained significant after a stringent correction for the total number of tests performed.
We also observed a significant interaction in which ADHD symptoms positively predicted wild/crazy AE only in youth with the 7-repeat DRD4 genotype; the same interaction marginally predicted sedated/impaired AE.
In this study, we take a dimensional perspective of ADHD and examine the relationship of this DRD4 polymorphism in a sample of children selected from the general population on the basis of high and low scores on the five ADHD items of the Strengths and Difficulties Questionnaire (SDQ) as rated by their parents.
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.
We observed a significant increase in the DRD4 7 repeat allele amongst ADHD probands (21.7%) and their parents (18.9% in mothers, 22.3% in fathers), compared to ethnically matched controls (12.8%).
The authors infer that the age of onset of ADHD may at least partially be affected by DRD5 variants warranting further investigation on the role of DRD5 in the disease etiology.