Dean W. Beebe

Background: Children and youth with Neurofibromatosis type 1 (NF1) commonly experience motor, behavioral, and cognitive problems. Promising findings from an NF1 mouse model suggested that the antioxidant N-acetylcysteine (NAC) might address underlying mechanistic deficits.Methods: We conducted a 12-week (8-week treatment, 4-week washout), double-blind, placebo-controlled randomized trial of NAC in 8–16-year-olds with NF1. We screened 481 children, identified 203 eligible, and randomized 25; 23 received at least one dose (10 NAC at ~70 mg/kg/day; 13 placebo). Outcomes were safety, tolerability, motor function (primary: Physical and Neurological Examination for Subtle Signs), cognitive function (secondary: Attention Deficit/Hyperactivity Disorder symptom scores and executive function measures), and exploratory biomarkers (Transcranial Magnetic Stimulation and Magnetic Resonance Spectroscopy measures).Results: NAC was generally well tolerated, although two participants were withdrawn by parents because of worsening behavior. In completer analyses, NAC did not improve any clinical outcome or biomarker at 8 weeks. Test-retest reliability of scales, measures, and biomarkers over 12 weeks was generally moderate.Conclusions: NAC was generally well tolerated but did not improve motor or behavioral outcomes in youth with NF1. Larger, longer trials with preceding dose-escalation and target-engagement studies are needed to evaluate new therapies.

Purpose: This study examined whether increasing sleep duration was associated with changes in daily affect, specifically, increases in positive affect (PA) and decreases in negative affect (NA), among short-sleeping adolescents. Methods: Healthy, short-sleeping adolescents (reporting <8 h sleep on school nights based on parent and adolescent screening questionnaires, n = 41, 14-17 years) participated in 1 week of baseline monitoring, then were randomized to either sleep extension (EXT; +90 min in bed; n = 21) or habitual sleep (HAB; n = 20) for 2 weeks. Both conditions established fixed bedtime and rise-time to reduce sleep variability. Sleep duration was assessed via wrist actigraphy. Participants completed the 22-item Profile of Mood States twice daily: soon after waking and at bedtime during the 3-week protocol. Results: During the initial preintervention week, average nightly sleep duration was 6.42 h (SD = 1.16). In the experimental weeks, HAB averaged 6.22 h (SD = 0.95), while EXT increased to 7.00 h (SD = 0.68; P = .002). This between-group difference represented a large effect (Hedges’ g ≈ 0.87), confirming that the manipulation increased sleep duration. Morning PA increased significantly in both conditions (P < .001). There were no significant differences in morning or evening affect between the EXT and HAB conditions. Adolescents experienced lower morning NA after nights when they slept longer, based on a secondary analysis conducted in the full sample, regardless of the experimental condition (P = .005). Further, adolescents with higher average sleep duration had lower evening PA regardless of the experimental condition (P = .03). Morning PA increased from baseline to the experimental weeks in both conditions. Unexpectedly, higher between-person total sleep duration was associated with diminished evening PA, emphasizing the nuanced role of sleep patterns in shaping affective states. Conclusions: Increasing nightly sleep is feasible for short-sleeping adolescents and resulted in longer sleep duration. Although affect did not differ between groups over the short intervention period, daily associations suggest that sleep may play a role in adolescents’ emotional experiences. Longer or more intensive sleep interventions may be needed to detect group-level changes in affect.

Despite extensive research on the effects of sleep restriction on adolescent health, the field lacks experimental methods to study the health effects of mistimed sleep, which is also common among adolescents. This paper describes a novel 3-week experimental protocol that was designed to compare sleep restriction, like what many adolescents experience on school nights, against sleep that meets the recommended duration but is timed to be relatively aligned or misaligned with their circadian phase. Healthy 14–18-year-olds, classified as early (“Lark”) and late (“Owl”) chronotypes, entered a six-night chronotype-aligned stabilization condition, followed by five nights of sleep restriction, a return to the stabilization schedule, and five nights of healthy sleep duration (HS). During HS, participants were randomly assigned to early-to-bed versus late-to-rise arms, intended to align with or misalign with their circadian phase. Actigraphy monitored sleep, and weekly dim-light melatonin onset (DLMO) assessed circadian phase. Analyses confirmed that the protocol met five key validation metrics related to differential attrition, sleep timing, circadian phase, and experimental induction of HS that is timed to be relatively aligned vs. misaligned with circadian phase. This protocol appears useful for future research into how misaligned sleep patterns, which occur regularly for many adolescents, may impact health.

Objective: Despite varying opinions, little research has examined how to best write pediatric neuropsychology reports. Method: This study gathered input from 230 parents on how text difficulty (reading level) and visual emphasis (bullets, underline, italics) affect report readability and utility. We focused on the most-read report section: summary/impressions. Each parent rated the readability and usefulness of a generic summary/impressions section written in four different styles. The four styles crossed text difficulty (high school-vs-collegiate) with use of visual emphasis (absent-vs-present). Results: Parents found versions with easier text to be more clearly written, easier to follow, and easier to find information (p<.001). Parents rated those with harder text to be overly detailed, complex, hard to understand, and hard to read (p<.001). Visual emphasis made it easier to find key information and the text easier to follow and understand - but primarily for versions that were written in difficult text (interaction p≤.026). After rating all four styles, parents picked their preference. They most often picked versions written in easier text with visual emphasis (p<.001). Conclusions: Findings support writing styles that use easier text difficulty and visual emphasis.

This study examines the impact of sleep duration, bedtime, and sleep disturbance during early childhood on the risk of cardiometabolic disorder (CMD) in early adolescence. Within the Health Outcomes and Measures of Environment (HOME) Study, we examined sleep patterns of 330 children from ages 2 to 8 years and the relationship of these sleep patterns with cardiometabolic risk measures at age 12 (N = 220). We used a group-based semi-parametric mixture model to identify distinct trajectories in sleep duration, bedtime timing, and sleep disturbance for the entire sample. We then examined the associations between sleep trajectories and CMD risk measures using general linear models using both an unadjusted model (no covariates) and an adjusted model (adjusting for child pubertal stage, child sex, duration of breastfeeding, household income, maternal education, and maternal serum cotinine). In the unadjusted and adjusted models, we found significant differences in CMD risk scores by trajectories of sleep disturbance. Children in the ‘high’ disturbance trajectory had higher CMD risk scores than those in the ‘low’ disturbance trajectory (p’s=.002 and 0.039, respectively). No significant differences in CMD risk were observed for bedtime timing or total sleep time trajectories in the unadjusted or adjusted models. In this cohort, caregiver-reported sleep disturbance in early childhood was associated with more adverse cardiometabolic profiles in early adolescence. Our findings suggest that trials to reduce CMD risk via sleep interventions – which have been conducted in adolescents and adults – may be implemented too late.