An Integrated Model of Executive Functioning is Helpful for Understanding ADHD and Associated Disorders.

OBJECTIVE: The aim of this study is to test the discriminative capacity of executive function (EF) tasks to better define the cognitive functioning of children with ADHD and comorbidities. METHOD: One hundred four children were presented with a battery of new EF tasks and a rating scale filled out by parents. RESULTS: Preliminary analysis of the neuropsychological tasks revealed the presence of five factors: Speed of Processing, Inhibition, Planning, Execution, and Retrospective Memory. All children with ADHD were impaired in Execution (a measure describing the capacity to achieve a goal). ADHD-only children were specifically impaired in Planning, while ADHD + reading disorder (RD) children were impaired in Speed of Processing and Retrospective Memory. Children with ADHD + oppositional defiant disorder (ODD) did not show impairment in any other EF domains. The five EF processes correlated with the EF Questionnaire. CONCLUSION: The present study describes different cognitive profiles in children with ADHD with or without comorbid disorders using neuropsychological EF measures.

Atomoxetine hydrochloride in the treatment of children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: A placebo-controlled Italian study.

OBJECTIVE: The primary aim of this study was to assess the efficacy of atomoxetine in improving ADHD and ODD symptoms in paediatric patients with ADHD and comorbid oppositional defiant disorder (ODD), non-responders to previous psychological intervention with parent support. METHODS: This was a multicentre, randomised, placebo-controlled trial conducted in patients aged 6-15 years, with ADHD and ODD diagnosed according to the DSM-IV criteria by a structured clinical interview (K-SADS-PL). Only subjects who are non-responders to a 6-week standardized parent training were randomised to atomoxetine (up to 1.2 mg/kg/day) or placebo (in a 3:1 ratio) for the following 8-week double blind phase. RESULTS: Only 2 of the 156 patients enrolled for the parent support phase (92.9% of males; mean age: 9.9 years), improved after the parent training program; 139 patients were randomised for entering in the study and 137 were eligible for efficacy analysis. At the end of the randomised double blind phase, the mean changes in the Swanson, Nolan and Pelham Rating Scale-Revised (SNAP-IV) ADHD subscale were -8.1+/-9.2 and -2.0+/-4.7, respectively in the atomoxetine and in the placebo group (p<0.001 between groups); changes in the ODD subscale were -2.7+/-4.1 and -0.3+/-2.6, respectively in the two groups (p=0.001 between groups). The CGI-ADHD-S score decreased in the atomoxetine group (median change at endpoint: -1.0) compared to no changes in the placebo group (p<0.001 between groups). Statistically significant differences between groups, in favour of atomoxetine, were found in the CHIP-CE scores for risk avoidance domain, emotional comfort and individual risk avoidance subdomains. An improvement in all the subscales of Conners Parents (CPRS-R:S) and Teacher (CTRS-R:S) subscales was observed with atomoxetine, except in the cognitive problems subscale in the CTRS-R:S. Only 3 patients treated with atomoxetine discontinued the study due to adverse events. No clinically significant changes of body weight, height and vital signs were observed in both groups. CONCLUSIONS: Treatment with atomoxetine of children and adolescents with ADHD and ODD, who did not initially respond to parental support, was associated with improvements in symptoms of ADHD and ODD, and general health status. Atomoxetine was well tolerated.

Use of atomoxetine in patients with attention-deficit hyperactivity disorder and co-morbid conditions.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioural disorders in children. It has been shown that as many as 85% of patients with ADHD have at least one psychiatric co-morbidity, and approximately 60% have at least two. Atomoxetine is a specific, noradrenergic reuptake inhibitor that provides an effective treatment option for patients with ADHD and co-morbid conditions. The efficacy of atomoxetine in treating ADHD appears to be unaffected by the presence of co-morbid conditions. Therapy with atomoxetine has been associated with statistically significant improvements in symptoms of oppositional defiant disorder in most, but not all, studies. Limited data suggest this agent may have potential in improving co-occurring symptoms of anxiety and may be useful in patients with co-morbid conditions such as tics or Tourette's syndrome. The tolerability profile of atomoxetine in patients with ADHD and co-morbid conditions was similar to that of patients with uncomplicated ADHD. Atomoxetine was well tolerated, with adverse events generally mild and transient; the most frequent adverse events in patients with ADHD included abdominal pain, decreased appetite, nausea and vomiting. The favourable safety and efficacy profile of atomoxetine makes it a promising treatment for patients with ADHD and associated co-morbidities.

Mutational analysis of EFHC1 gene in Italian families with juvenile myoclonic epilepsy.

OBJECTIVES: Mutations in the EFHC1 gene have been reported in six juvenile myoclonic epilepsy (JME) families from Mexico and Belize. In this study, we screened 27 unrelated JME Italian families for mutations in the EFHC1 gene. MATERIALS AND METHODS: Twenty-seven families (86 affected individuals, 52 women) with at least two affected members with JME were selected. DNA was isolated from peripheral blood lymphocytes by standard methods and each exon of the EFHC1 gene was amplified and sequenced using intronic primers. RESULTS: Two heterozygous mutations were identified in three unrelated families. One (R353 W) was a novel missense mutation, while the F229 L mutation was previously described (say which on of the two occurred in two families). Both mutations cosegregated with the disease. In a fourth family, the variant 545G-->A (resulting in the amino acid substitution R182 H) cosegregated with JME. CONCLUSIONS: The results of our study extend the distribution of EFHC1 mutations to the white population and confirm the high level of genetic heterogeneity associated with JME.