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).
Increased density of dopamine transporter in ADHD brains, along with abundance of 7-repeat D4 receptors in prefrontal cortex, which is impaired in ADHD patients, make the observed gene-gene interaction worthy of further incisive studies.
It is now established that certain alleles of the genes coding for the dopamine D4 receptor and the dopamine transporter occur more frequently in children with ADHD than in healthy controls, and we are finding other DNA changes associated with ADHD.
Genetic variants of the SLC6A3 gene that encodes the human dopamine transporter (DAT) have been linked to a variety of neuropsychiatric disorders, particularly attention deficit hyperactivity disorder.
The goal of this study was to evaluate whether ADHD risk alleles at DRD4 and DAT1 genes could predict the change in striatal DAT occupancy after treatment with MPH in adolescents with ADHD/SUDs.
Positive findings of association of the dopamine transporterDAT1 480 bp allele (allele 10) and the DRD4 7 repeat allele with clinical ADHD have been previously reported.
A logistic regression analysis showed that the simultaneous absence of the 10/10 DAT1 and 7/7 DRD4 genotypes predicts membership to the group of ADHD patients with internalized comorbidities (e.g. anxiety, depression).
Use of symptom scores as continuous scales in regression analysis suggested that the combination of mother and teacher ratings yielded the strongest evidence for association between hyperactive-impulsive ADHD symptoms and DAT1 and between inattentive ADHD symptoms and DRD4.
To remedy this situation, we have pursued the creation of a mouse model derived from a functional nonsynonymous variant in the DAT gene (SLC6A3) of ADHD probands.
(2006); Arch Ger Psychiatry 63:462-469] recently reported a potentially important association between two dopamine-related risk polymorphisms (DRD4 variable number tandem repeat (VNTR) in exon 3 and DAT1 VNTR in the 3' UTR) and lowered IQ in ADHD.
These are of interest for treating de novo loss-of-function mutations of DAT associated with neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD).
Further replication and functional studies are now required to fully understand the consequence of polymorphisms present at both the 5' and 3' ends of the DAT1 gene and their role in ADHD pathophysiology.
To examine whether psychosocial adversity moderated the effect of genetic variation in DAT1 on ADHD symptoms in adolescents from a high-risk community sample.
Recent meta-analyses have indicated that the dopamine transporter gene (DAT1) and the dopamine receptor genes D4 (DRD4) and D5 (DRD5) are associated with attention-deficit hyperactivity disorder (ADHD), although single studies frequently failed to show significant association.
Three genetic risk factors for ADHD (DRD4 7-repeat allele of the exon 3 variable number of tandem repeats (VNTR), DAT1 10/10 genotype of the VNTR located in the 3' untranslated region, and the DAT1 6/6 genotype of the intron 8 VNTR) were included in the analyses.
Our findings provide initial evidence for the involvement of the epigenetic alterations of DAT1 in modulating the response to MPH treatment in ADHD, primarily on oppositional and hyperactive-impulsive symptoms.
The DAT1 40bp VNTR 9/10 polymorphism pairing appears to be reliably associated with greater symptoms of ADHD and externalizing behavior from childhood to adulthood, and with family, educational, and occupational impairments.
This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD).
However, a significantly higher perfusion in the right middle temporal gyrus was found in the group with risk alleles at both DRD4 and DAT1 loci (n = 6) compared to ADHD boys without risk alleles at both loci (n = 28) (P < 0.05).
10/10 DAT allele seems to be associated with an increased expression level of the dopamine transporter and seems to mediate the MPH treatment response in ADHD patients.
Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH.