Sleep Problems and Trajectories of Restricted and Repetitive Behaviors in Children with Neurodevelopmental Disabilities.
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ABSTRACT:
SUBMITTER: MacDuffie KE
PROVIDER: S-EPMC10513108 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Sleep Problems and Trajectories of Restricted and Repetitive Behaviors in Children with Neurodevelopmental Disabilities.
MacDuffie Katherine E KE Munson Jeffrey J Greenson Jessica J Ward Teresa M TM Rogers Sally J SJ Dawson Geraldine G Estes Annette A
Journal of autism and developmental disorders 20201101 11
Sleep problems are prevalent in children with neurodevelopmental disabilities and are associated with the expression of restricted and repetitive behaviors (RRBs). Children (n = 57) with autism spectrum disorder (ASD, n = 38) or developmental delay (DD, n = 19) participated in multiple assessments of intellectual ability, ASD symptoms, and RRBs (3 timepoints for ASD, 2 for DD). Sleep problems assessed at age 4 via parent report were associated with trajectories of higher-order RRBs (sameness/rit ...[more]
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Project description:BackgroundClinical evidence is required about the long-term efficacy and safety of melatonin treatment for sleep problems in children with neurodevelopmental disorders (NDDs) who underwent adequate sleep hygiene interventions.MethodsWe conducted a 26-week, multicenter, collaborative, uncontrolled, open-label, phase III clinical trial of melatonin granules in children 6 to 15 years of age who had NDDs and sleep problems. The study consisted of the 2-week screening phase, the 26-week medication phases I and II, and the 2-week follow-up phase. Children received 1, 2, or 4 mg melatonin granules orally in the medication phases. Variables of sleep status including sleep onset latency (SOL), aberrant behaviors listed on the Aberrant Behavior Check List-Japanese version (ABC-J), and safety were examined. The primary endpoint was SOL in the medication phase I.ResultsBetween June 2016 and July 2018, 99 children (80 males and 19 females, 10.4 years in mean age) were enrolled at 17 medical institutions in Japan-74, 60, 22, 9, 6, and 1 of whom had autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disabilities, motor disorders, specific learning disorder, and communication disorders, respectively, at baseline. Fifteen children received the maximal dose of 4 mg among the prespecified dose levels. SOL recorded with the electronic sleep diary shortened significantly (mean ± standard deviation [SD], - 36.7 ± 46.1 min; 95% confidence interval [CI], - 45.9 to - 27.5; P < 0.0001) in the medication phase I from baseline, and the SOL-shortening effect of melatonin persisted in the medication phase II and the follow-up phase. Temper upon wakening and sleepiness after awakening improved significantly (P < 0.0001 each) in the medication phase I from baseline and persisted in the follow-up phase. The following subscales of the ABC-J improved significantly: stereotypic behavior (P = 0.0322) in the medication phase I; and irritability, hyperactivity, and inappropriate speech (P < 0.0001) in the medication phase II. Treatment-emergent adverse events did not occur subsequent to week 16 after medication onset, and NDDs did not deteriorate in the follow-up phase.ConclusionsLong-term melatonin treatment in combination with adequate sleep hygiene interventions may afford clinical benefits to children with NDDs and potentially elevates their well-being.Trial registrationClinicalTrils.gov , NCT02757066 . Registered April 27, 2016.
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Project description:Development of the sleep-wake rhythm has a significant effect on the physical and mental development of children. The sleep-wake rhythm is controlled by aminergic neurons in the brainstem's ascending reticular activating system, which is associated with synaptogenesis and the promotion of brain development. The sleep-wake rhythm develops rapidly within the first year after birth. At 3-4 months of age, the framework of the circadian rhythm is established. The objective of the present review is to assess a hypothesis concerning problems in the development of the sleep-wake rhythm and their effect on neurodevelopmental disorders. Autism spectrum disorder is characterised by a delay in the development of sleep rhythms at 3-4 months of age and also insomnia and night-time awakenings, as supported by several reports. Melatonin may shorten the sleep latency in ASD. Rett syndrome sufferers kept awake during the daytime were analysed by the Sleep-wake Rhythm Investigation Support System (SWRISS) (IAC, Inc., (Tokyo, Japan)), and the cause was found to be the dysfunction of aminergic neurons. Children and adolescents with attention deficit hyperactivity disorder show sleep problems such as resistance to bedtime, difficulty falling asleep, sleep apnoea, and restless legs syndrome. Sleep deprivation syndrome in schoolchildren is deeply influenced by Internet use, games, and smartphones, and this syndrome affects emotion, learning, concentration, and executive functioning. Sleep disorders in adults are strongly considered to affect not only the physiological/autonomic nervous system but also neurocognitive/psychiatric symptoms. Even adults cannot avoid serious problems, much less children, and the impact of sleep problems is considerably greater in adults. Paediatricians and nurses should be aware of the significance, from birth, of sleep development and sleep hygiene education for carers and parents. This research was reviewed and approved by the ethical committee of the Segawa Memorial Neurological Clinic for Children (No. SMNCC23-02).
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Project description:ObjectiveTo assess the effectiveness and safety of melatonin in treating severe sleep problems in children with neurodevelopmental disorders.Design12 week double masked randomised placebo controlled phase III trial.Setting19 hospitals across England and Wales.Participants146 children aged 3 years to 15 years 8 months were randomised. They had a range of neurological and developmental disorders and a severe sleep problem that had not responded to a standardised sleep behaviour advice booklet provided to parents four to six weeks before randomisation. A sleep problem was defined as the child not falling asleep within one hour of lights out or having less than six hours' continuous sleep.InterventionsImmediate release melatonin or matching placebo capsules administered 45 minutes before the child's bedtime for a period of 12 weeks. All children started with a 0.5 mg capsule, which was increased through 2 mg, 6 mg, and 12 mg depending on their response to treatment.Main outcome measuresTotal sleep time at night after 12 weeks adjusted for baseline recorded in sleep diaries completed by the parent. Secondary outcomes included sleep onset latency, assessments of child behaviour, family functioning, and adverse events. Sleep was measured with diaries and actigraphy.ResultsMelatonin increased total sleep time by 22.4 minutes (95% confidence interval 0.5 to 44.3 minutes) measured by sleep diaries (n=110) and 13.3 (-15.5 to 42.2) measured by actigraphy (n=59). Melatonin reduced sleep onset latency measured by sleep diaries (-37.5 minutes, -55.3 to -19.7 minutes) and actigraphy (-45.3 minutes, -68.8 to -21.9 minutes) and was most effective for children with the longest sleep latency (P=0.009). Melatonin was associated with earlier waking times than placebo (29.9 minutes, 13.6 to 46.3 minutes). Child behaviour and family functioning outcomes showed some improvement and favoured use of melatonin. Adverse events were mild and similar between the two groups.ConclusionsChildren gained little additional sleep on melatonin; though they fell asleep significantly faster, waking times became earlier. Child behaviour and family functioning outcomes did not significantly improve. Melatonin was tolerable over this three month period. Comparisons with slow release melatonin preparations or melatonin analogues are required.Trial registrationISRCT No 05534585.
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Project description:Restricted and repetitive behaviors (RRBs) are a defining clinical feature of autism spectrum disorders (ASD). RRBs are highly heterogeneous with variable expression of circumscribed interests (CI), insistence of sameness (IS) and repetitive motor actions (RM), which are major impediments to effective functioning in individuals with ASD; yet, the neurobiological basis of CI, IS and RM is unknown. Here we evaluate a unified functional brain circuit model of RRBs and test the hypothesis that CI and IS are associated with aberrant cognitive control circuit dynamics, whereas RM is associated with aberrant motor circuit dynamics. Using task-free fMRI data from 96 children, we first demonstrate that time-varying cross-network interactions in cognitive control circuit are significantly reduced and inflexible in children with ASD, and predict CI and IS symptoms, but not RM symptoms. Furthermore, we show that time-varying cross-network interactions in motor circuit are significantly greater in children with ASD, and predict RM symptoms, but not CI or IS symptoms. We confirmed these results using cross-validation analyses. Moreover, we show that brain-clinical symptom relations are not detected with time-averaged functional connectivity analysis. Our findings provide neurobiological support for the validity of RRB subtypes and identify dissociable brain circuit dynamics as a candidate biomarker for a key clinical feature of ASD.
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Project description:BackgroundRestricted and repetitive behaviors (RRBs) are core features of autism spectrum disorder (ASD) and one of the earliest behavioral signs of ASD. However, RRBs are also present in typically developing (TD) infants, toddlers, and preschool-aged children. Past work suggests that examining change in these behaviors over time is essential to distinguish between normative manifestations of these behaviors and behaviors that denote risk for a neurodevelopmental disorder. One challenge in examining changes in these behaviors over time is that most measures of RRBs have not established longitudinal measurement invariance. The aims of this study were to (1) establish measurement invariance in the Repetitive Behavior Scales for Early Childhood (RBS-EC), a parent-report questionnaire of RRBs, and (2) model developmental change in RRBs from 8 to 36 months.MethodsWe collected RBS-EC responses from parents of TD infants (n = 180) from 8 to 36 months (n = 606 responses, with participants contributing an average of 3-time points). We leverage a novel methodological approach to measurement invariance testing (Bauer, Psychological Models, 22(3), 507-526, 2017), moderated nonlinear factor analysis (MNLFA), to determine whether the RBS-EC was invariant across age and sex. We then generated adjusted factor score estimates for each subscale of the RBS-EC (repetitive motor, self-directed, and higher-order behaviors), and used linear mixed effects models to estimate between- and within-person changes in the RBS-EC over time.ResultsThe RBS-EC showed some non-invariance as a function of age. We were able to adjust for this non-invariance in order to more accurately model changes in the RBS-EC over time. Repetitive motor and self-directed behaviors showed a linear decline from 8 to 36 months, while higher-order behaviors showed a quadratic trajectory such that they began to decline later in development at around 18 months. Using adjusted factor scores as opposed to unadjusted raw mean scores provided a number of benefits, including increased within-person variability and precision.ConclusionsThe RBS-EC is sensitive enough to measure the presence of RRBs in a TD sample, as well as their decline with age. Using factor score estimates of each subscale adjusted for non-invariance allowed us to more precisely estimate change in these behaviors over time.
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Project description:We examined the relations of restricted and repetitive behaviors (RRB; insistence on sameness, repetitive sensory-motor, self-injurious behavior) to social skills overall and aspects that comprise social skills as measured by the VABS-II (coping skills, play/leisure time, interpersonal relationships) in 24- (n = 63) and 36-month old (n = 35), high-familial-risk toddlers with ASD. Hierarchical linear regression results indicated that repetitive sensory-motor was the best predictor of social skills overall. Secondary results indicated that all three RRB subtypes were associated with each subdomain of social skills; however, repetitive sensory-motor was the strongest and most consistent among these effects. While our results suggests a general negative relation of subtypes of RRB to aspects of adaptive social function, repetitive sensory-motor behaviors may be of particular relevance to the development of social skills during toddlerhood.
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