Attention deficit hyperactivity disorder and cardiovascular functioning.

The dopamine transporter (DAT) plays a key role in the regulation of dopaminergic neurotransmission and is also the major site of action for methylphenidate which is one of the main drugs used to treat attention deficit hyperactivity disorder (ADHD). Most association studies with ADHD have concentrated on the 3'-untranslated region of the gene (3'-UTR) mainly in a variable number of tandem repeat (VNTR) polymorphism, but these investigations have reported discordant results. In this study, we tested this VNTR polymorphism and an additional promoter polymorphism -839 C>T (Rs: 2652511) using family-based association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No significant linkage disequilibrium between the two polymorphisms was detected in this sample (D' = 0.56; P = 0.22). No evidence of association with the VNTR polymorphism was found. A significant association (P = 0.03) for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the ADHD combined type (P = 0.004). Our results suggest a role for the promoter region of DAT1 gene in ADHD susceptibility in this Brazilian sample.

Attention Deficit Disorder with Hyperactivity↗

PubMed2007

The functional impact of SLC6 transporter genetic variation.

Solute carrier 6 (SLC6) is a gene family of ion-coupled plasma membrane cotransporters, including transporters of neurotransmitters, amino acids, and osmolytes that mediate the movement of their substrates into cells to facilitate or regulate synaptic transmission, neurotransmitter recycling, metabolic function, and fluid homeostasis. Polymorphisms in transporter genes may influence expression and activity of transporters and contribute to behavior, traits, and disease. Determining the relationship between the monoamine transporters and complex psychiatric disorders has been a particular challenge that is being met by evolving approaches. Elucidating the functional consequences of and interactions among polymorphic sites is advancing our understanding of this relationship. Examining the influence of environmental influences, especially early-life events, has helped bridge the gap between genotype and phenotype. Refining phenotypes, through assessment of endophenotypes, specific behavioral tasks, medication response, and brain network properties has also improved detection of the impact of genetic variation on complex behavior and disease.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Examining subtypes of behavior problems among 3-year-old children, Part I: investigating validity of subtypes and biological risk-factors.

This study examined 3-year-old children who were classified as hyperactive (HYP), oppositional-defiant (OD), hyperactive and oppositional defiant (HYP/OD), and non-problem based on mothers' reports of behavior. Using fathers,' teachers,' and observers' ratings of children's behavior, concurrent validity was excellent for the HYP/OD group, moderate for the HYP group, and poor for the OD group. As predicted, both the HYP/OD and HYP groups reported more prenatal/perinatal birth complications and a greater family history of hyperactivity than did non-problem children. Furthermore, the HYP/OD group showed a greater family history of conduct disorder and oppositional defiant disorder (ODD) symptoms than did non-problem children; however, the HYP group also showed a greater family history of ODD than did non-problem children. Results suggest that as early as age 3, these behavior subtypes appear to be linked to biologically-based risk-factors in ways that are consistent with theories of the development of ADHD.

Attention Deficit Disorder with Hyperactivity↗