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Neurofibromatosis type 1 is a common genetic disorder characterised by neurocutaneous manifestations and cognitive and behavioural problems. Statins were shown to reduce analogous learning deficits in a mouse model of the disease, but a short-term trial in humans was inconclusive. We aimed to assess the use of simvastatin for the improvement of cognitive and behavioural deficits in children with neurofibromatosis type 1 for 12 months. In this randomised, double-masked, placebo-controlled trial, we recruited children with genetically confirmed neurofibromatosis type 1 aged 8–16 years from two national referral centres in the Netherlands and Belgium. Those with symptomatic CNS abnormalities or on neurotropic medication, including stimulants, were excluded. Eligible patients were randomly assigned (1:1) via a computer-generated, permuted-block list to simvastatin (10 mg per day in month 1, 20 mg per day in month 2, and 20–40 mg per day in months 3–12) or placebo for 12 months. Investigators, participants, and parents were masked to treatment assignment. Primary outcome measures were full-scale intelligence (Wechsler intelligence scale for children), attention problems (child behaviour checklist, parent-rated [CBCL]), and internalising behavioural problems (CBCL). We did intention-to-treat analyses (of all patients who had outcome data) using linear regression of the 12 month outcome scores, adjusted for baseline performance. This trial is registered with the Netherlands Trial Register, number NTR2150. We randomly assigned 84 children to a treatment group (43 to simvastatin, 41 to placebo) between March 9, 2010, and March 6, 2012. We did not assess outcomes in two patients in the placebo group because they needed additional drug therapy. Simvastatin for 12 months had no effect on full-scale intelligence (treatment effect compared with placebo −1·3 IQ points [95% CI −3·8 to 1·3]; p=0·33), attention problems (–1·6 T-score points [–4·3 to 1·0]; p=0·23), and internalising behavioural problems (–0·1 T-score points [–3·3 to 3·1]; p=0·96). 38 (88%) of 43 patients on simvastatin and 39 (95%) of 41 patients on placebo reported adverse events, which were serious in two and four patients, respectively. 12 month simvastatin treatment did not ameliorate cognitive deficits or behavioural problems in children with neurofibromatosis type 1. The use of 20–40 mg simvastatin per day for cognitive enhancement in children with neurofibromatosis type 1 is not recommended. The Netherlands Organization for Health Research and Development (ZonMw), Research Foundation Flanders (FWO-Vlaanderen), Marguerite-Marie Delacroix Foundation, and the Dutch Neurofibromatosis Association (NFVN).

There is growing evidence that insufficient sleep has negative effects on the mental health of children. The aim of this study is to examine the associations between device-measured sleep duration and internalizing and externalizing problems in 8-year-old children. The study is a secondary analysis of data from the Childhood Obesity Project conducted in five European countries. Nocturnal sleep duration was measured with the SenseWear™ Armband 2. Parents rated their child’s internalizing and externalizing problems on the Child Behaviour Checklist. Behaviour scores were dichotomized at the 90th percentile based on sex- and country-specific z -scores. Logistic regression models were applied to test the associations between sleep duration and behaviour. Data were available for 406 8-year-old children. The average sleep duration was 9.25 h per night (SD: 0.67) with 1464 nights measured in total. The sleep duration recommendation of the American Academy of Sleep Medicine for school-aged children (9–12 h) was met by 66.7% of children. One hour of additional sleep per night significantly reduced the risk of having internalizing problems (adjusted OR = 0.51; 95% CI 0.29–0.91). Children who adhered to the sleep duration recommendation had a lower risk for internalizing problems (adjusted OR = 0.45; 95% CI 0.21–0.99). Sleep duration and externalizing problems showed no significant association. Longer sleep duration was associated with a reduced risk of having internalizing problems but not externalizing problems. Results highlight that it is important to ensure adequate sleep duration throughout primary-school years for the optimal emotional health of children. Trial registration number: NCT00338689. Registered: June 19, 2006.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by social and language deficits and by repetitive behaviors and interests. Irritability/aggression is a significant comorbid symptom in this population, which greatly impacts burden of care. This study examined the effect of divalproex sodium for irritability/aggression in children and adolescents with ASD. This was a 12-week randomized, double-blind, placebo-controlled trial. All efficacy measures were obtained by an independent evaluator blinded to randomization condition and side effects. A total of 55 subjects gavetheir consent and 27 were randomized in a 1 : 1 manner (mean age 9.46±2.46, mean nonverbal IQ 63.3±23.9). Two subjects from the active group and one subject from the placebo group discontinued the study because of either a lack of efficacy or side effects (increased irritability). Primary outcome measures were Aberrant Behavior Checklist-Irritability subscale and Clinical Global Impression-Improvement, which focused on irritability. Overall, 62.5% of divalproex subjects vs 9% of placebo subjects were responders (CGI-irritability OR: 16.7, Fisher's exact p =0.008). A statistically significant improvement was also noted on the ABC-Irritability subscale ( p =0.048). There was a trend for responders to have higher valproate blood levels compared with nonresponders. This study suggests the efficacy of divalproex for the treatment of irritability in children and adolescents with ASD. Larger sample follow-up studies are warranted.

Computerized working memory and executive function training programs designed to target specific impairments in executive functioning are becoming increasingly available, yet how well these programs generalize to improve functional deficits in disorders, such as attention-deficit/hyperactivity disorder (ADHD), beyond the training context is not well-established. The aim of this study was to examine the extent to which working memory (WM) training in children with ADHD would diminish a core dysfunctional behavior associated with the disorder, “off-task” behavior during academic task performance. The effect of computerized WM training (adaptive) was compared to a placebo condition (nonadaptive) in a randomized, double-blind, placebo-controlled design in 26 children (18 males; age, 7 to 14 years old) diagnosed with ADHD. Participants completed the training in approximately 25 sessions. The Restricted Academic Situations Task (RAST) observational system was used to assess aspects of off-task behavior during the completion of an academic task. Traditional measures of ADHD symptoms (Conners' Parent Rating Scale) and WM ability (standardized WM tests) were also collected. WM training led to significant reductions in off-task ADHD-associated behavior on the RAST system and improvement on WM tests. There were no significant differences between groups in improvement on parent rating scales. Findings lend insight into the generalizability of the effects of WM training and the relation between deficits in WM and off-task behavioral components of ADHD. These preliminary data suggest WM training may provide a mechanism for indirectly altering academic performance in children with ADHD.

Background Children with borderline to mild intellectual disability (BMID) have been shown to be at increased risk for psychosocial problems. The presence of these psychosocial problems leads to parenting stress. Stepping Stones Triple P (SSTP) is a parenting support program to support parents with children with BMID and psychosocial problems. The aim of this study was to evaluate the effectiveness of SSTP compared to Care as Usual (CAU) in reducing psychosocial problems in children with BMID. Method We conducted a randomized controlled trial in the Northern provinces of the Netherlands. Parents of children aged 5 to 12 with borderline (IQ 70 to 85) or mild (IQ 70 to 50) ID and psychosocial problems were invited. Psychosocial problems were identified using the Strengths and Difficulties Questionnaire (SDQ) parent report (≥14). Measurements were assessed before the intervention (T0), immediately after the intervention (T1) and after a follow-up of six months (T2). SSTP takes 8 to 10 individual sessions of 40-90 minutes, provided over 10 to 12 weeks. CAU concerned any service, except SSTP. Primary outcomes were the child’s psychosocial problems (SDQ parent and teacher forms and the Eyberg Child Behavior Inventory, ECBI). Secondary outcomes were parenting stress (Parenting Stress Index, PSI) and parenting skills (Alabama Parenting Questionnaire, APQ). Results In total 209 parents of children aged 5 to 12 with BMID were allocated blindly to either SSTP (n =111) or CAU (n =98). In the intention to treat analyses, SSTP achieved no significantly better effect than CAU for the SDQ parent report, the ECBI and the APQ on the short- and long- term. In the short term, SSTP was significantly more effective than CAU for the SDQ teacher report (B = -2.25, 95% CI -3.79 to -0.71) and the PSI (B = -7.06, 95% CI -12.11 to -2.01). For both SDQ teacher report and PSI, there was no statistically significant effect in the long term. Dropout from SSTP was considerable (49%), with the effects being solely found in the adherent SSTP subgroup. Conclusions SSTP had some short-term advantages over CAU, but not in the longer term. Trial registration Dutch Trial Register NTR2624 . Registered 26 November 2010

In this volume leading behavioral scientists describe advances in our understanding of the multiple biopsychosocial regulatory processes underlying the development of children's behavior disorders. A full spectrum of regulatory influences is addressed, ranging from genes to cultural factors. Individual chapters highlight the importance of developing research paradigms that synthesize biological, behavioral, and social-ecological influences, and of viewing self-regulation as a complex system that reorganizes across development. The regulatory foundations of a diverse range of childhood behavior problems are examined, including anxiety, social withdrawal, depression, conduct problems, inattention and impulsivity, and sleep problems.

Background/Aims: To evaluate effects of growth hormone (GH) treatment on behaviour and psychosocial characteristics in short-stature children. Methods: 99 referred prepubertal non-familiar short-stature children (32 GH deficiency; 67 idiopathic short stature) aged 3–11 years, randomized to fixed or individual GH doses and their parents completed questionnaires (Child Behaviour Checklist, Birleson Depression Self-Report Scale, Abbreviated Parent-Teacher Questionnaire, I Think I Am, Well-Being Visual-Analogue Scales for Short-Stature Children) at baseline (BL) and after 3, 12, and 24 months. Results: At BL, children showed higher levels of internalizing behaviour (p < 0.001), lower levels of externalizing behaviour (p < 0.006) and self-esteem (p < 0.001) compared to reference values. During GH treatment, behavioural measures (p < 0.001) and depression (p < 0.01) changed towards the mean of the population within the first 3 months and remained improved to 24 months. Self-esteem improved at all time points (p < 0.001), and in all subgroups, as did well-being dimensions stability and mood (p < 0.05). Multiple regression analysis showed that greater improvements were related to lower BL value, height gain, higher maximal GH value, being older, and being male. Conclusion: On GH treatment, prepubertal short children significantly improved on behavioural, depression, and psychosocial evaluations over a 2-year period of GH treatment. Most change occurred within the first 3 months, which highlights this short period as important not only for growth and metabolic changes but also for behaviour and psychosocial improvements following GH treatment.

Objective: Although high-grade intraventricular hemorrhage (IVH; grades III–IV) in preterm and low birth weight infants are clearly associated with increased risk of long-term adverse neurodevelopmental sequelae, the impact of low-grade IVH (grades I–II) has been less clear. Some studies have followed these infants through early school age and have shown some conflicting results regarding cognitive outcome. Such studies that assess children at younger ages may not accurately predict outcomes in later childhood, as it is known that fluid and crystallized intelligence peak at age 26 years. There is paucity of data in current medical literature, which correlates low-grade IVH with outcomes in early adulthood. To determine the link between the occurrence of low-grade IVH in low birth weight (birth weight ⩽2500 g) infants born prematurely (gestational age <37 weeks) and intellectual function, academic achievement, and behavioral problems to the age of 18 years. Study Design: This study is an analysis of data derived from the Infant Health and Development Program (IHDP), a multisite national collaborative study and a randomized controlled trial of education intervention for low birth weight infants from birth until 3 years of age with follow-up through 18 years of age. A total of 985 infants were enrolled in the IHDP. Of the 462 infants tested for IVH, 99 demonstrated sonographic evidence of low-grade IVH, whereas 291 showed no sonographic evidence of IVH. Several outcomes were compared between these two groups. Intelligence was assessed using Stanford–Binet Intelligence scales at age 3 years, Wechsler Intelligence Scale for Children (WISC-III) at age 8 years, Wechsler Abbreviated Scale of Intelligence (WASI) at age 18 years and Woodcock Johnson Tests of Achievement at age 8 and 18 years. Behavior was measured using the Achenbach Behavior Checklist at age 3 years and Child Behavior Checklist (CBCL) at age 8 and 18 years. Outcomes were compared between the IVH-positive and IVH-negative groups using analysis of covariance after adjusting for the presence or absence of intervention, birth weight, gestational age, gender, severity of neonatal course, race and maternal education. Results: No statistically significant difference in intelligence as measured by Stanford–Binet Intelligence scales, WISC-III, WASI and Woodcock–Johnson Tests of Achievement could be appreciated between IVH-positive patients and controls at any age group (36 months, 8 years and 18 years of age). In addition, there was no significant difference in problem behavior as assessed by the Achenbach Behavior Checklist and Child Behavior Checklist (CBCL) comparing IVH patients with controls. Conclusion: Low-grade IVH was not demonstrated in our study to be an independent risk factor associated with lower outcomes in intelligence, academic achievement or problem behavior at age 3, 8 and 18 years.

IntroductionChildren with autistic spectrum disorder (ASD) often have associated behavioural difficulties that can present a challenge for parents and parenting. There are several effective social learning theory-based parenting programmes for dealing with behavioural difficulties, including the Incredible Years (IY) parent programmes. However, these programmes typically do not specifically target parents of children with ASD. Recently, a new addition to the IY suite of programmes known as the IY Autistic Spectrum and Language Delays (IY-ASLD) parent programme was developed. The main aims of the present study are to examine the feasibility of delivering this programme within child health services and to provide initial evidence for effectiveness and economic costs.Methods and analysisThe Parenting for Autism, Language, And Communication Evaluation Study (PALACES) trial is a pragmatic, multicentre, pilot randomised controlled trial comparing the IY-ASLD programme with a wait-list control condition. 72 parents of children with ASD (aged 3–8 years) will be randomly allocated to either the intervention or control condition. Data will be collected prior to randomisation and 6 months postrandomisation for all families. Families in the intervention condition only will also be followed up at 12 and 18 months postrandomisation. This study will provide initial evidence of effectiveness for the newly developed IY-ASLD parenting programme. It will also add to the limited economic evidence for an intervention targeting parents of children with ASD and provide longer term data, an important component for evaluations of parenting programmes.Ethics and disseminationApproval for the study was granted by the Research Ethics Committee at the School of Psychology, Bangor University (reference number: 2016–15768) and the North Wales Research Ethics Committee, UK (reference number: 16/WA/0224). The findings will be disseminated through research conferences and peer-reviewed journals.Trial registration numberISRCTN57070414; Pre-results.