No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent and highly heritable childhood disorder. The dopamine D4 receptor (DRD4) gene has shown a genetic association with ADHD in Caucasian populations with meta-analysis indicating a small but significant effect across datasets. It remains uncertain whether this association can be generalised to non-Caucasian ethnic groups. Here we investigate two markers within the DRD4 gene in a Taiwanese population, the exon 3 variable number tandem repeat (VNTR) and a 5' 120 base-pair duplication. METHODS: Within-family transmission disequilibrium tests of association of the 5' 120 base-pair duplication, and exon 3 VNTR in a Taiwanese population. RESULTS: No evidence of association of ADHD with either polymorphism in this population was observed. CONCLUSION: The DRD4 gene markers investigated were not found to be associated with ADHD in this Taiwanese sample. Further work in Taiwanese and other Asian populations will therefore be required to establish whether the reports of association of DRD4 genetic variants in Caucasian samples can be generalised to Asian populations

Association of 4-Repeat Allele of the Dopamine D4 Receptor Gene Exon III Polymorphism and Response to Methylphenidate Treatment in Korean ADHD Children

In the present study, we investigated the association between the 4-repeat allele at the dopamine receptor D4 (DRD4) gene and the response to treatment with methylphenidate (MPH) in Korean children with attention deficit hyperactivity disorder (ADHD). The study subjects were 83 children with ADHD (8.40+/-1.73 years) who were recruited from two child psychiatric clinics in South Korea. All of the drug-naive ADHD children were treated with MPH for about 8 weeks. An improvement of more than or equal to [corrected] 50% in the ADHD Rating Scale-IV (ARS) scores after 8 weeks of treatment compared with the baseline ARS scores before the treatment was considered as a 'good response', whereas an improvement of less than [corrected] 50% was considered as a 'poor response'. After the genotyping for DRD4 was performed, we investigated the association between the genotype at DRD4 and the response to MPH treatment. We performed a comparison of the response to MPH treatment between the two largest groups, viz. the subjects with and without the 4/4 genotype at DRD4. According to the ARS scores of the subjects as assessed by their parents and by their teachers, we found that while 71.1 and 80.0% (32/45 and 24/30), respectively, of those with a good response to MPH treatment showed the 4/4 genotype at DRD4, only 31.6 and 37.7% (12/38 and 20/53), respectively, of those with a poor response to MPH treatment showed the 4/4 genotype at DRD4 (Pearson chi2-values=12.926 and 13.737, respectively, both df=1, and both p<0.01). Our findings support the existence of an association between the 4-repeat allele at DRD4 and good response to MPH in Korean ADHD children

Prevalence of attention deficit/hyperactivity disorder among adults in obesity treatment

<p>Abstract</p> <p>Background</p> <p>Bariatric patients showing poor "focus" during treatment more often failed to lose weight or maintain reduced weight. Evaluation of these patients identified a number having attention deficit/hyperactivity disorder (ADHD), evidently a potent factor limiting successful weight control. After searches found no published reports describing comorbid ADHD and obesity, this report was conceived to begin exploring the prevalence and characteristics of these patients.</p> <p>Method</p> <p>Clinical records of 215 patients receiving obesity treatment during 2000 were reviewed. Data collected and analyzed included age, sex, beginning and ending body mass index (BMI), number of clinic visits, months of treatment, and diagnostic category (ADHD, some ADHD symptoms, non-ADHD). DSM-IV criteria were used, except age of onset was modified to <= 12 years.</p> <p>Results</p> <p>Whole sample ADHD prevalence was 27.4% (CI:21.1,32.9), but 42.6% (CI: 36.3% to 48.9%) for BMI >= 40. Mean weight loss among obese patients with ADHD (OB+ADHD) was 2.6 BMI (kg/m²) vs. 4.0 for non-ADHD (NAD) (p < 0.002). For BMI >= 40, OB+ADHD had BMI loss 2.9 vs. 7.0 (NAD) (p < 0.004). OB+ADHD had more clinic visits, with a trend toward longer treatment duration.</p> <p>Conclusions</p> <p>ADHD was highly prevalent among obese patients and highest in those with extreme obesity. Comorbid obesity and ADHD symptoms rendered treatment less successful compared to NAD counterparts. Reasons for the comorbidity are unknown, but may involve brain dopamine or insulin receptor activity. If replicated in further studies, these findings have important implications for treatment of severe and extreme obesity.</p

Serotoninergics Attenuate Hyperlocomotor Activity in Rats. Potential New Therapeutic Strategy for Hyperactivity

Hyperactivity is thought to be associated with an alteration of dopamine (DA) neurochemistry in brain. This conventional view became solidified on the basis of observed hyperactivity in DA-lesioned animals and effectiveness of the dopaminomimetics such as amphetamine (AMP) in abating hyperactivity in humans and in animal models of hyperactivity. However, because AMPreleases serotonin (5-HT) as well as DA, we investigated the potential role of 5-HT in an animal model of hyperactivity. We found that a greater intensity of hyperactivity was produced in rats when both DA and 5-HT neurons were damaged at appropriate times in ontogeny. Therefore, previously we proposed this as an animal model of attention deficit hyperactivity disorder (ADHD) - induced by destruction of dopaminergic neurons with 6-hydroxydopamine (6-OHDA (neonatally) and serotoninergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) (in adulthood). In this model effects similar to that of AMP(attenuation of hyperlocomotion) were produced by m-chlorophenylpiperazine (m-CPP) but not by 1-phenylbiguanide (1-PG), respective 5-HT2 and 5-HT3 agonists. The effect of m-CPP was shown to be replicated by desipramine, and was largely attenuated by the 5-HT2 antagonist mianserin. These findings implicate 5-HT neurochemistry as potentially important therapeutic targets for treating human hyperactivity and possibly childhood ADHD

Genes de suscetibilidade no transtorno de déficit de atenção e hiperatividade Susceptibility genes in attention/deficit hyperactivity disorder

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.<br>Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood and adolescence, affecting 3%-6% of school age children. It is characterized by symptoms of inattention, hyperactivity and impulsivity, showing also a high clinical heterogeneity. Although the precise causes of ADHD are unclear, the influence of genetic factors is strongly suggested by epidemiologic studies, that provide evidences for a large number of investigations with candidate genes. Nowadays, despite the great attention driven to this subject, no gene can be considered as necessary or sufficient to the development of ADHD, and the search for genes that affect this process is still the focus of many investigations. Thus, the objective of this paper is to summarize and discuss the main results on the research with possible susceptibility genes for ADHD

The “outer dimensions”: impulsivity, anger/aggressiveness, activation

The “outer” SVARAD dimensions, impulsivity, anger/aggressiveness, and activation, represent trans-diagnostic psychological and behavioural domains that span traditional categorical boundaries. At the neurobiological level, the fronto-limbic and the fronto-cerebellar circuitry, as well as molecular pathways involving dopamine, serotonin, testosterone, and inflammatory mediators, play a crucial role in mediating the biological underpinnings of these psychopathological dimensions. From a clinical perspective, as the combination of clusters of symptoms differs from patient to patient and gives rise to a wide variety of clinical pictures even among subjects with the same diagnosis, it is important that the clinical features related to impulsivity, anger, aggressiveness, and activation are specifically and multiparametrically investigated and treated. The aim of the present chapter is to discuss the psychopathological aspects, the neurobiological underpinnings, and the clinical implications related to the “outer dimensions” in clinical psychiatry