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Van Der Meer J.M.J.,Karakter Child and Adolescent Psychiatry University Center | Van Der Meer J.M.J.,Donders Institute for Brain | Oerlemans A.M.,Karakter Child and Adolescent Psychiatry University Center | Oerlemans A.M.,Donders Institute for Brain | And 7 more authors.
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2012

Objective: Autism spectrum disorders (ASD) and attention-deficit/ hyperactivity disorder (ADHD) frequently co-occur. Given the heterogeneity of both disorders, several more homogeneous ASD-ADHD comorbidity subgroups may exist. The current study examined whether such subgroups exist, and whether their overlap or distinctiveness in associated comorbid symptoms and cognitive profiles gives support for a gradient overarching disorder hypothesis or a separate disorders hypothesis. Method: Latent class analysis was performed on Social Communication Questionnaire (SCQ) and Conners' Parent Rating Scale (CPRS-R:L) data for 644 children and adolescents (5 through 17 years of age). Classes were compared for comorbid symptoms and cognitive profiles of motor speed and variability, executive functioning, attention, emotion recognition, and detail-focused processing style. Results: Latent class analysis revealed five classes: two without behavioral problems, one with only ADHD behavior, and two with both clinical symptom levels of ASD and ADHD but with one domain more prominent than the other (ADHD[+ASD] and ASD[+ADHD]). In accordance with the gradient overarching disorder hypothesis were the presence of an ADHD class without ASD symptoms and the absence of an ASD class without ADHD symptoms, as well as cognitive functioning of the simple ADHD class being less impaired than that of both comorbid classes. In conflict with this hypothesis was that there was some specificity of cognitive deficits across classes. Conclusions: The overlapping cognitive deficits may be used to further unravel the shared etiological underpinnings of ASD and ADHD, and the nonoverlapping deficits may indicate why some children develop ADHD despite their enhanced risk for ASD. The two subtypes of children with both ASD and ADHD behavior will most likely benefit from different clinical approaches. © 2012 American Academy of Child and Adolescent Psychiatry.


Harfterkamp M.,University of Groningen | Van De Loo-Neus G.,Karakter Child and Adolescent Psychiatry University Center | Minderaa R.B.,University of Groningen | Van Der Gaag R.-J.,Karakter Child and Adolescent Psychiatry University Center | And 6 more authors.
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2012

The efficacy of atomoxetine as treatment of symptoms of attention-deficit/hyperactivity disorder (ADHD) in patients with autism spectrum disorder (ASD) has not been established. In this study, 97 patients aged 6 to 17 years with ADHD and ASD were randomly assigned to double-blind treatment with 1.2 mg/kg/day atomoxetine or placebo for 8 weeks. The primary endpoint was the ADHD Rating Scale (ADHD-RS) score; secondary endpoints were the Clinical Global Impression of ADHD-Improvement (CGI-I) and the Conners Teacher Rating Scale-Revised: Short Form (CTRS-R:S) score. Baseline mean ADHD-RS scores for atomoxetine versus placebo were 40.7 and 38.6; after 8 weeks, mixed-effect model repeated-measure means were 31.6 (95% confidence interval 29.2-33.9) and 38.3 (36.0-40.6), respectively, with a difference in least square means of -6.7 (-10.0 to -3.4; p < .001). The CTRS-R:S Hyperactivity subscore also improved significantly for atomoxetine compared with placebo, but not the other CTRS-R:S subscores. However, there were not significantly more patients on atomoxetine (20.9%) who improved much, or very much according to the CGI-I, than on placebo (8.7%; p = 0.14). Adverse events (mostly nausea, decrease in appetite, fatigue, and early morning awakening) were reported in 81.3% of atomoxetine patients and 65.3% of placebo patients (p > .1). There were no serious adverse events. Atomoxetine moderately improved ADHD symptoms in patients with ASD and was generally well tolerated. Adverse events in this study were similar to those in other studies with ADHD patients without ASD. Clinical trial registration information--A Randomized Double-Blind Study of Atomoxetine Versus Placebo for ADHD Symptoms in Children with ASD; www.clinicaltrials.gov; NCT00380692. © 2012 American Academy of Child and Adolescent Psychiatry.


Buitelaar J.,UMC St Radboud | Buitelaar J.,Karakter Child and Adolescent Psychiatry University Center
European Child and Adolescent Psychiatry | Year: 2010

Attention-deficit/hyperactivity disorder (ADHD), one of the most common neuropsychiatric conditions of childhood, often has a chronic course and persists into adulthood in many individuals. ADHD may have a clinically important impact on health-related quality of life in children, a significant impact on parents' emotional health and interfere with family activities/cohesion. To date, the main targets of ADHD treatment have focused on reducing the severity of symptoms during the school day and improving academic performance. However, the treatment of ADHD should reach beyond symptom control to address the issues of social competencies and improvement of health-related quality of life from the perspectives of individuals with ADHD and their families, to support them in reaching their full developmental potential. Methylphenidate (MPH) is recognised as the first-line choice of pharmacotherapy for ADHD in children and adolescents. This paper focuses on the importance and benefits to child development of ADHD symptom control beyond the school day only, i.e. extending into late afternoon and evening and uses the example of an extended-release MPH formulation (OROS® MPH) to demonstrate the potential benefits of active full day coverage (12 h) with a single daily dose. Concerns of long-term stimulant treatment are also discussed. © 2009 The Author(s).


Oosterling I.,Karakter Child and Adolescent Psychiatry University Center
Journal of child psychology and psychiatry, and allied disciplines | Year: 2010

The Social Communication Questionnaire (SCQ) is a screening instrument with established validity against the Autism Diagnostic Interview-Revised (ADI-R) in children aged 4 years and older. Indices of diagnostic accuracy have been shown to be strong in school-aged samples; however, relatively little is known about the performance of the SCQ in toddlers at risk of autism spectrum disorder (ASD). This study replicates and extends previous research by Corsello et al. (2007) in a comparatively large (N = 208), substantially younger (20-40 months) sample of children at high risk of ASD. The usefulness of the SCQ as a second-level screening instrument with different cut-off scores was evaluated in relation to IQ, age, and type of ASD diagnosis. The use of the SCQ as compared to the ADI-R was evaluated against clinical diagnosis, both alone and in combination with the ADOS. The SCQ with different cut-offs consistently showed an unsatisfactory balance between sensitivity and specificity in screening for ASD in high-risk toddlers, with only a few exceptions for specific age, IQ, or diagnostic groups. Even though the SCQ and ADI-R were highly correlated, diagnostic agreement with the best evidence clinical diagnosis was poor for both measures. The ADOS used alone consistently had the highest predictive value. For autism versus not-autism, the combined SCQ and ADOS performed as well as the ADOS alone and notably better than the combination ADI-R and ADOS. The SCQ is likely to result in a number of false-positive findings, particularly in children with autism symptomatology, and the balance between sensitivity and specificity is poor. The ADOS should be considered the most valid and reliable diagnostic instrument in these very young at-risk children. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.


Van Der Schaaf M.E.,Radboud University Nijmegen | Fallon S.J.,Radboud University Nijmegen | Ter Huurne N.,Radboud University Nijmegen | Buitelaar J.,Radboud University Nijmegen | And 2 more authors.
Neuropsychopharmacology | Year: 2013

Increased use of stimulant medication, such as methylphenidate, by healthy college students has raised questions about its cognitive-enhancing effects. Methylphenidate acts by increasing extracellular catecholamine levels and is generally accepted to remediate cognitive and reward deficits in patients with attention deficit hyperactivity disorder. However, the cognitive-enhancing effects of such 'smart drugs' in the healthy population are still unclear. Here, we investigated effects of methylphenidate (Ritalin, 20 mg) on reward and punishment learning in healthy students (N=19) in a within-subject, double-blind, placebo-controlled cross-over design. Results revealed that methylphenidate effects varied both as a function of task demands and as a function of baseline working memory capacity. Specifically, methylphenidate improved reward vs punishment learning in high-working memory subjects, whereas it impaired reward vs punishment learning in low-working memory subjects. These results contribute to our understanding of individual differences in the cognitive-enhancing effects of methylphenidate in the healthy population. Moreover, they highlight the importance of taking into account both inter- and intra-individual differences in dopaminergic drug research.

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