We documented the effect of the G allele at the ADRA2A -1291 C>G polymorphism on the improvement of inattentive symptoms with methylphenidate treatment in children and adolescents with ADHD. Our findings provide clinical evidence for the involvement of the noradrenergic system in the modulation of methylphenidate action.

Few studies on pharmacogenetics of Attention-Deficit/Hyperactivity Disorder (ADHD) have been conducted. Most of them evaluated dopaminergic genes resulting in positive and negative findings. We assessed effects of polymorphisms in candidate dopaminergic (DRD4, DAT1) and serotonergic genes (HTR1B, HTR2A, and 5-HTT) on the response to treatment in 111 patients for whom methylphenidate (MPH) was prescribed. Outcome measures (Swanson, Nolan, and Pelham scale-version IV, Children Global Assessment Scale, Barkley's Stimulants Side Effects Rating Scale) were assessed at baseline and 1 month after the intervention. No significant association was detected between polymorphisms assessed and both response and side effects to MPH. Prospective multi-site controlled studies with larger sample sizes are needed in order to disentangle the role of candidate genes in response to ADHD treatment.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood. The role of genetic factors in its etiology is strongly supported by family, adoption, and twin studies. Low serotonin activity has been associated in both animal and human studies with measures of impulsivity, aggression, and disinhibited behaviors, which make genes from the serotonin system reasonable candidates for ADHD susceptibility. In the present study, we investigated a polymorphism in the promoter region of the serotonin transporter (SLC6A4) and two polymorphisms (À1438 A > G and His452-Tyr) in the serotonin 5-HTR2A receptor gene using family based association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No linkage disequilibrium between the two HTR2A polymorphisms was detected in this sample (P ¼ 0.76). Considering several evidences from animal models for sexual dimorphism in serotonin genes expression, analyses were performed separately for the whole sample and for male probands. No evidences for biased transmissions of both HTR2A À1438 A > G and SLC6A4 polymorphisms to ADHD youths were observed. Preferential transmission of the HTR2A His452 allele was observed only in families with affected boys (P ¼ 0.04). Our results suggest that findings from ADHD association studies for serotonin genes might be understood in the context of a gender effect, which may help to explain conflicting results in these association studies. INTRODUCTIONAttention deficit hyperactivity disorder (ADHD) is a highly heritable condition it is relatively common in childhood, affecting 8%-12% of children worldwide. In clinically referred samples of children, ADHD affects three times more males than females [Rohde et al., 1999;Biederman and Faraone, 2005], while epidemiological studies report a ratio of 2:1 [Arcia and Conners, 1998]. Family, twin, and adoption studies strongly support a role for genetic components in the etiology of the disorder [Biederman and Faraone, 2005].The dopaminergic and the noradrenergic systems have been extensively implicated in the pathophysiology of ADHD [Biederman and Faraone, 2005]. Nevertheless, the serotonergic system has also been recently implicated in the etiology of ADHD. The serotonin neurotransmitter (5-HT) is involved in the regulation of a broad array of psychological, behavioral, and biological functions that when disregulated influence the development and course of an equally broad range of psychiatric and medical disorders. Reduced central serotonergic activity has been implicated, for example, in the mediation of negative emotions, poor impulse regulation, aggressive behavior, increased use of alcohol and nicotine, and increased food consumption in animals and humans [Halperin et al., 1997;Lucki, 1998]. The role of the serotonergic system in ADHD is also supported by a study showing that platelet 5-HT levels were relatively low in a sample of children with severe ADHD [Spivak et al., 1999].Moreover, animal studies also indicated that fr...

The monoamine oxidase A (MAOA) gene has been extensively related to aggressive, impulsive and violent behaviours. Previous studies have documented the improvement of oppositional symptoms in attention deficit hyperactivity disorder (ADHD) patients with methylphenidate (MPH). However, the effect of the MAOA gene in response to MPH has not been investigated. A sample of 85 boys from an ADHD outpatient service was genotyped for the MAOA-uVNTR polymorphism. The outcome measure was the parent-rated oppositional subscale of the Swanson, Nolan and Pelham Scale - version IV. The scale was applied by child psychiatrists blinded to genotype at baseline and in the first and third months of treatment. A significant interaction between the presence of MAOA high-activity genotype and treatment with MPH over time on oppositional scores was detected during the 3 months' treatment (n=85, F2,136=4.83, p=0.009). These results suggest an effect of the MAOA-uVNTR high-activity genotype on the improvement of oppositional symptoms with MPH treatment.

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Mosquitos são responsáveis pela transmissão de várias doenças causadas por vírus, parasitas e helmintos. Considerando o custo e a complexidade do tratamento dessas doenças, o uso de repelentes para proteção contra mosquitos vetores se torna uma alternativa interessante. Nesse contexto, no presente trabalho foram feitos estudos por ancoramento e dinâmica molecular (DM) de potenciais ligantes da proteína odorante do mosquito Anopheles gambiae (AgOBP 1 ), o principal vetor da malária. Os modos de ligação na AgOBP 1 de moléculas com conhecida atividade atrativa e dos principais componentes do óleo do cravo da índia (Syzygium aromaticum), com potencial atividade repelente, foram comparados com o conhecido repelente N,N-dietil-3-metilbenzamida (DEET). Os resultados sugerem que o acetato de eugenila é um repelente melhor do que o DEET e também revelam as principais características do sítio de ligação da AgOBP 1 importantes para o planejamento de novos e mais eficientes repelentes.Mosquitoes are responsible for conveying various diseases caused by viruses, parasites and helminthes. Considering the cost and complexity of the treatment of these diseases, the use of repellents for protection from the mosquito vectors becomes an interesting alternative. In the present work, docking and molecular dynamics (MD) studies were performed on potential ligands to the odorant binding protein of the mosquito Anopheles gambiae (AgOBP 1 ), the main vector of malaria. The binding modes on AgOBP 1 of molecules with known attractive activities and the main components of the oil of indian clove (Syzygium aromaticum) with potential repellent activities were compared to the known repellent N, . Results suggest the eugenyl acetate as a better repellent than DEET and also reveal the main features of the binding site of AgOBP 1 important to the design of new and more efficient repellents.

Several evidences suggested that the serotonin 5-HT1B receptor gene (HRT1B) might be involved in the susceptibility to attention deficit/hyperactivity disorder (ADHD). Prior studies reported excess transmissions of the HRT1B gene 861G allele to affected ADHD children and of a haplotype block containing this variant and two functional promoter SNPs to probands with ADHD-inattentive subtype. However, some investigations did not replicate these findings. Therefore, we tested for biased transmissions of haplotypes derived from the 861G > C, -161A > T, and -261T > G SNPs from parents to 343 families with ADHD children. We also sought to replicate findings from the literature that the association between HTR1B is preferentially with ADHD-Inattentive subtype. Using a transmission disequilibrium test we found evidence for an excess transmission of haplotype. -261G/-161T/861G (P = 0.014) for affected children in the total sample. When the analysis was repeated with 143 families with ADHD-Inattentive subtype no significant associations were observed. Our results provide additional evidence that HRT1B gene may be an important risk factor for the development of ADHD, but this effect seems not to be attributable to inattentive cases.