Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes.
However, no DAT residue able to discriminate ADHD drugs' addictiveness is identified, and the way how different drug structures affect their abuse liability is still elusive.
In conclusion, by regulation of glucocorticoid receptor, GR agonist can decrease DAT expression, resulting in the increase of DA and NE levels in brain that ameliorate hyperactivity and attention deficit in ADHD rats.
After correcting for multiple testing, we found several significant associations between the polymorphisms and ADHD (p value corrected ≤0.05): (1) SLC6A4 and LPHN3 were associated in the total population; (2) SLC6A2, SLC6A3, SLC6A4 and LPHN3 were associated in the combined subtype; and (3) LPHN3 was associated in the male sample.
This study aimed to assess the role of the catechol-O-methyltransferase (<i>COMT</i>) and of the dopamine transporter (<i>DAT1</i>) genes on ADHD symptoms in the general population.
Regression analyses revealed that in the IMpACT cohort, and not in the other cohorts, carriers of the DAT1 adult ADHD risk haplotype 9-6 had 5.9 % larger striatum volume relative to participants not carrying this haplotype.
In a large observational ADHD cohort study (N = 316), the effects of cumulative stimulant treatment, genotype (for DAT1 haplotype and DRD4 variants), and treatment-by-genotype interactions on striatal, frontal, and hippocampal volumes and their interactions with age were evaluated.
Polymorphisms in genes such as DAT1, 5HTTLPR, D4DR4, and MAO-A have been linked to attention deficit hyperactivity disorder (ADHD) and susceptibility for opiate addiction.
Our results thus suggest that the 10R allele as the DAT1 gene VNTR polymorphism might be associated with MPH-related changes in brain metabolites in adults with 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).
In this study, we demonstrate a link between an ADHD-associated DAT mutation (Arg615Cys, R615C) and variation on DAT transporter cell surface dynamics, a combination only previously studied with ensemble biochemical and optical approaches that featured limited spatiotemporal resolution.
To determine the association between the VNTR of DAT1 and the phenotype of ADHD or its endophenotypes in a sample of children aged between 6 and 15 years from Bogotá.
Present findings suggest that cortical thickness of right lateral prefrontal cortex (BA 46) is influenced by the presence of the DAT1 10 repeat allele in children and adolescents with ADHD.
Although these neural activation changes were associated with different task performance measures, no relationship was found between DAT1 or COMT variants and ADHD, nor did variants in these genes explain variance in the effects of ADHD on neural activation.
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.
Our finding of the haplotype rs403636 (G)/rs463379 (C)/rs393795 (C)/rs37020 (G) as a novel genetic marker for spatial working memory suggests that variation in DAT1 may provide insight into the pathways leading from genotype to phenotype of ADHD.
Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies.
The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD).
Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3'-UTR 9/10 VNTR, rs27072 in the 3'-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD.
Here we present results of a meta-analysis of studies investigating the moderating effect of the SLC6A3 VNTR on response to methylphenidate treatment in subjects with ADHD.