QTL association analysis of the DRD4 exon 3 VNTR polymorphism in a population sample of children screened with a parent rating scale for ADHD symptoms.
ABSTRACT Current developments in molecular genetics have led to a rapid increase in research aimed at the identification of genetic variation that influences complex human phenotypes. One phenotype that has aroused a great deal of interest is the behavioral trait hyperactivity and the related clinical disorder attention-deficit hyperactivity disorder (ADHD). The driving force behind the molecular genetic research in this area is the overwhelming evidence from quantitative genetic studies that show high heritablility (h(2) = 0.7-0.9) for the behaviors characterizing the diagnosis of ADHD, whether the disorder is viewed as a categorical entity or a continuous trait. To date, molecular studies have aimed at identifying susceptibility genes for ADHD, defined using operational diagnostic criteria, and have focused on variation within genes that regulate dopamine neurotransmission. Several studies report ADHD to be associated with the 7-repeat allele of a 48 bp repeat polymorphism (DRD4-7) in exon 3 of the dopamine D4 receptor gene (DRD4). 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. We found a significant relationship between DRD4-7 and high-scoring individuals [chi-square = 8.63; P = 0.003; OR = 2.09 (95% CI 1.24 < OR < 3.54), F-statistic = 7.245; P = 0.008].
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ABSTRACT: O transtorno de déficit de atenção e hiperatividade (TDAH) é um dos transtornos mais comuns da infância e adolescência, afetando entre 3% a 6% das crianças em idade escolar. Essa patologia caracteriza-se por sintomas de desatenção, hiperatividade e impulsividade, apresentando ainda uma alta heterogeneidade clínica. Embora as causas precisas do TDAH não estejam esclarecidas, a influência de fatores genéticos é fortemente sugerida pelos estudos epidemiológicos, cujas evidências impulsionaram um grande número de investigações com genes candidatos. Atualmente, apesar da ênfase dada a este tópico, nenhum gene pode ser considerado necessário ou suficiente ao desenvolvimento do TDAH, e a busca de genes que influenciam este processo ainda é o foco de muitas pesquisas. O objetivo desse artigo é, portanto, sumarizar e discutir os principais resultados das pesquisas com genes candidatos no TDAH.Revista Brasileira de Psiquiatria. 01/2002;
Article: Management of ADHD in adults.[show abstract] [hide abstract]
ABSTRACT: Although first identified in children in the 19th century, attention-deficit/hyperactivity disorder (ADHD) in adults was not described in the literature until 1976. The symptoms of adult ADHD resemble the symptoms of childhood ADHD, but symptom intensity, especially hyperactivity, may decrease over time. However, due to the challenges and responsibilities of adulthood, a normal day is extremely complicated for the ADHD adult. Molecular genetics and neuroimaging studies confirm that ADHD is a heterogeneous, neurobiological disorder, mainly of dopaminergic and noradrenergic pathways. Trials of pharmacologic treatments in adults with ADHD have produced mixed results due to considerable variability in diagnostic criteria, dosing, and response. This article reviews the history, neurobiology, and pharmacologic management of adult ADHD.The Journal of Clinical Psychiatry 02/2002; 63 Suppl 12:29-35. · 5.80 Impact Factor
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ABSTRACT: Attention deficit/hyperactivity disorder (ADHD) is a common and potentially very impairing neuropsychiatric disorder of childhood. Statistical genetic studies of twins have shown ADHD to be highly heritable, with the combination of genes and gene by environment interactions accounting for around 80% of phenotypic variance. The initial molecular genetic studies where candidates were selected because of the efficacy of dopaminergic compounds in the treatment of ADHD were remarkably successful and provided strong evidence for the role of DRD4 and DAT1 variants in the pathogenesis of ADHD. However, the recent application of non-candidate gene strategies (eg, genome-wide association scans) has failed to identify additional genes with substantial genetic main effects, and the effects for DRD4 and DAT1 have not been replicated. This is the usual pattern observed for most other physical and mental disorders evaluated with current state-of-the-art methods. In this paper we discuss future strategies for genetic studies in ADHD, highlighting both the pitfalls and possible solutions relating to candidate gene studies, genome-wide studies, defining the phenotype, and statistical approaches.Pharmacogenomics and Personalized Medicine 01/2010; 3:61-78.