Bleijenberg G.,Donders Center for Neuroscience |
Hendriks J.,Radboud University Nijmegen
Neurology | Year: 2014
Objective: To investigate the effect of aerobic exercise training (AET) and cognitive-behavioral therapy (CBT) on chronic fatigue in patients with facioscapulohumeral muscular dystrophy (FSHD). Methods: We performed a multicenter, assessor-blinded, randomized clinical trial (RCT). Fiftyseven patients with FSHD type 1 with severe chronic fatigue were randomly allocated to AET, CBT, or usual care (UC). Outcomes were assessed before treatment, following 16 weeks of intervention, and after a 12-week follow-up. A linear mixed model for repeated measurements was used to study the estimated group differences. Results: Following treatment, both the AET (28 participants) and CBT (25 participants) intervention groups had less fatigue relative to the UC group (24 participants), with a difference of 29.1 for AET (95% confidence interval [CI] 212.4 to 25.8) and 213.3 for CBT (95% CI 216.5 to 210.2). These beneficial effects lasted through follow-up, with a difference of 28.2 for AET (95% CI 212.4 to 25.8) and 210.2 for CBT (95% CI 214.0 to 26.3). The patients who received CBT had an increase in registered and experienced physical activity, sleep quality, and social participation. The patients who received AET had an increase in registered physical activity only. The increase in registered physical activity in both groups and the improvement in social participation following CBT were still present at follow-up. Conclusions: This RCT shows that AET and CBT can ameliorate chronic fatigue in patients with FSHD. Classification of evidence: This study provides Class III evidence that, in patients with FSHD type 1 and severe chronic fatigue, AET or CBT reduces the severity of chronic fatigue. © 2014 American Academy of Neurology.
Staal W.G.,Donders Center for Neuroscience |
Staal W.G.,Center for Child and Adolescent Psychiatry
European Neuropsychopharmacology | Year: 2015
The SNP rs167771 of the dopamine-3-receptor gene (DRD3) has been associated with autism spectrum disorder (ASD) in samples from the United Kingdom, The Netherlands and Spain. The DRD3 polymorphisms of rs167771 are significantly associated with a specific type of repetitive and stereotyped behavior, called sameness. Repetitive and stereotyped behavior occurs in several neuropsychiatric disorders and the combined picture across these disorders strongly suggests the involvement of the basal ganglia - frontal lobe circuitry. In autism, abnormalities of the basal ganglia, in particular the caudate nucleus, are the best replicated findings in neuroimaging studies. Interestingly, the DRD3 gene is highly expressed in the basal ganglia, most notably the caudate nucleus. The rs167771 SNP was recently also found to be related to risperidone-induced extra-pyramidal side effects (EPS) in patients with autism, which is important since risperidone is approved for the treatment of aggression, irritability and rigid behavior in ASD. To conclude, striatum abnormalities in autism are associated with repetitive and stereotyped behavior in autism and may be related to DRD3 polymorphisms. © 2014 Elsevier B.V. and ECNP.
PubMed | Karolinska Institutet, University of Newcastle, University of Bristol, Social Impact and 78 more.
Type: Journal Article | Journal: Nature | Year: 2016
Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
Dirks I.,Radboudumc |
Koene S.,Radboudumc |
Verbruggen R.,Donders Center for Neuroscience |
Smeitink J.A.M.,Radboudumc |
And 2 more authors.
Muscle and Nerve | Year: 2016
Introduction: The 6-minute walk test (6MWT) is frequently used as an outcome measure for clinical trials in neuromuscular disease. Because this submaximal endurance test is not feasible for nonambulatory patients, the motor-assisted 6-minute cycling test (A6MCT) was developed. Methods: Nineteen children with neuromuscular disorders and children with OXPHOS-dysfunction performed the a6MCT and the 6MWT to explore feasibility and construct validity. Test–retest reproducibility was evaluated within 3 weeks. Results: The assisted 6-minute cycling test was feasible in 90% and 78% of the patients with a neuromuscular disorder and OXPHOS-dysfunction, respectively. The A6MCT for legs correlated with the 6MWT in both patient groups. The assisted 6-minute cycling showed good reproducibility for both legs and arms. Conclusions: This exploratory study indicates that the assisted 6-minute cycling test is a promising outcome measure for patients with a neuromuscular disorder and patients with OXPHOS-dysfunction. Muscle Nerve, 2015. Muscle Nerve 54: 232–238, 2016. © 2016 Wiley Periodicals, Inc.
PubMed | Radboudumc and Donders Center for Neuroscience
Type: Journal Article | Journal: Muscle & nerve | Year: 2016
The 6-minute walk test (6MWT) is frequently used as an outcome measure for clinical trials in neuromuscular disease. Because this submaximal endurance test is not feasible for nonambulatory patients, the motor-assisted 6-minute cycling test (A6MCT) was developed.Nineteen children with neuromuscular disorders and children with OXPHOS-dysfunction performed the a6MCT and the 6MWT to explore feasibility and construct validity. Test-retest reproducibility was evaluated within 3 weeks.The assisted 6-minute cycling test was feasible in 90% and 78% of the patients with a neuromuscular disorder and OXPHOS-dysfunction, respectively. The A6MCT for legs correlated with the 6MWT in both patient groups. The assisted 6-minute cycling showed good reproducibility for both legs and arms.This exploratory study indicates that the assisted 6-minute cycling test is a promising outcome measure for patients with a neuromuscular disorder and patients with OXPHOS-dysfunction. Muscle Nerve, 2015. Muscle Nerve 54: 232-238, 2016.
Lelieveld S.H.,Radboud University Nijmegen |
Veltman J.A.,Donders Center for Neuroscience |
Veltman J.A.,Maastricht University |
Gilissen C.,Donders Center for Neuroscience
Human Genetics | Year: 2016
With the widespread adoption of next generation sequencing technologies by the genetics community and the rapid decrease in costs per base, exome sequencing has become a standard within the repertoire of genetic experiments for both research and diagnostics. Although bioinformatics now offers standard solutions for the analysis of exome sequencing data, many challenges still remain; especially the increasing scale at which exome data are now being generated has given rise to novel challenges in how to efficiently store, analyze and interpret exome data of this magnitude. In this review we discuss some of the recent developments in bioinformatics for exome sequencing and the directions that this is taking us to. With these developments, exome sequencing is paving the way for the next big challenge, the application of whole genome sequencing. © 2016 The Author(s)