Sleep in autism: A biomolecular approach to aetiology and treatment.

People with autism spectrum disorder (ASD) commonly experience other comorbidities. Studies indicate that between 50% and 83% of individuals with ASD have sleep problems or disorders. The most commonly reported sleep problems are: (a) insomnia symptoms including the inability to get to sleep or stay asleep; and (b) circadian rhythm sleep-wake disorders, defined as a misalignment between the timing of endogenous circadian rhythms and the external environment. The circadian system provides timing information for the sleep-wake cycle that is regulated by the interaction of an endogenous processes (circadian - Process C, and homeostatic - Process S) and synchronizing agents (neurohormones and neurotransmitters), which produce somnogenic activity. A clinical priority in ASD is understanding the cause of these sleep problems in order to improve treatment outcomes. This review approaches sleep in autism from several perspectives: Sleep-wake mechanisms and problems, and brain areas and molecules controlling sleep (e.g., GABA and melatonin) and wake maintenance (e.g., serotonin, acetylcholine and glutamate). Specifically, this review examines how altered sleep structure could be related to neurobiological alterations or genetic mutations and the implications this may have for potential pharmacological treatments in individuals with ASD.

A survey of sleep problems in autism, Asperger's disorder and typically developing children.

BACKGROUND: Sleep problems are common in typically developing (TD) children and in children with autism, however, less is known about the sleep of children with Asperger's disorder (AD). The aim of this study was to compare sleep patterns of children with autism and AD to a TD group of children. METHODS: Sixty-six parents of TD children, 53 parents of children with autism, and 52 parents of children with AD completed a survey on their child's sleep patterns, the nature and severity of any sleep problems and success of any treatment attempted. RESULTS: The results showed high prevalence of sleep problems with significantly more problems reported in the autism and AD groups (TD = 50%, autism = 73%, AD = 73%), with no significant differences between groups on severity or type of sleep problem. Children with AD were significantly more likely to be sluggish and disoriented after waking and had a higher Behavioral Evaluation of Disorders of Sleep (BEDS) total score compared to the other two groups. The autism and AD groups reported significantly better treatment success for medication compared to the TD group. The autism group reported significantly better success for behavioural treatment compared to the AD group. CONCLUSIONS: In conclusion, children with AD may have more symptoms of sleep disturbance, and different types of sleep problems than children with autism. As this is the first study to compare autism and AD and to survey treatment outcomes, further research is needed to validate these findings.

Sleep problems in children with an intellectual disability: parental perceptions of sleep problems, and views of treatment effectiveness.

BACKGROUND: Sleep problems are common in children with an intellectual disability (ID), often lasting for many years. Many parents do not perceive their child to have a sleep problem, do not believe treatment is possible and do not seek treatment. This paper examined prevalence and duration of sleep problems in children with an ID and considered parental perceptions of sleep problems and views towards treatment. METHOD: The paper reports on two studies (n = 149 and 243 respectively) of children between 3 and 18 years, with a range of disabilities. Parents in each study completed a questionnaire about their child's sleep problems, and the type and effectiveness of any treatment used to address their child's sleep problems. RESULTS: Prevalence rates ranged between 25.5% and 36.2% for sleep problems with an average duration of between 6 and 9 years. Around half of parents had sought treatment for their child's sleep problem in Study 1, while 76% had done so in Study 2. Parental ratings regarding treatment effectiveness were higher in Study 1 than in Study 2. Contrary to expectations, behavioural treatment was not rated as significantly more effective than other treatments in either study. CONCLUSIONS: While sleep problems are common and chronic in children with an ID, parents may not recognize a sleep problem as present, often do not seek treatment for their child's sleep problems, and treatment advice and effectiveness is very variable. Thus, further research and parent and professional education regarding the identification and treatment of sleep problems in these children is required.

Treatment of sleep problems in a 5-year-old boy with autism using behavioural principles.

This article presents a case study which is part of a larger project on sleep problems in children with autism. The successful treatment of sleep problems (night settling, night waking, and co-sleeping) in a boy of 5 years 4 months with autism is described. The intervention was based on behavioural principles and involved the parents attending an individually-run parent training programme. The programme consisted of an interview, three weekly training sessions and a review session. The parents learned how to use a bedtime routine, reinforcement, effective instructions, partner support strategies and extinction procedures. Once the techniques were implemented, the child learned how to settle himself to bed and how to sleep alone for the entire night. For this child, the results of the sleep programme were clinically significant as measured by a scale of goal achievement, and were maintained at a 3 month and a 12 month follow-up.

Sleep and behaviour disturbance in Prader-Willi syndrome: a questionnaire study.

The present authors describe sleep problems, including sleep apnoea and excessive daytime sleepiness (EDS), in subjects with Prader-Willi syndrome (PWS). The present paper reports a questionnaire study regarding sleep and behaviour in a group of 29 subjects with PWS, compared with an age- and gender-matched control group. Those with PWS suffered from sleep problems more frequently than the control subjects. Problems included EDS, snoring and early waking. Sleep problems in PWS were not associated with body mass index or weight. Excessive daytime sleepiness was a distinctive feature of the group with PWS, and behavioural disturbance in PWS children and adolescents was associated with EDS. Excessive daytime sleepiness seems to be characteristic of PWS, and may be related to problems with the sleep-wake cycle and hypothalamic dysfunction.

An investigation into sleep characteristics of children with autism and Asperger's Disorder.

OBJECTIVE: The aim of the study was to investigate the specificity of sleep problems in children with autism and further explore the currently unclear association between sleep problems and daytime behaviour. METHODOLOGY: The Pervasive Developmental Disorder (PDD) group consisted of 31 children with autism and 7 children with Asperger's Disorder ranging in age from 44 to 152 months. The control group consisted of 36 children ranging in age from 63 to 171 months. The children were matched on age and gender, and group-matched on IQ level. A sleep diary was completed by parents over a 2-week period, in addition to several behaviour questionnaires. RESULTS: Results showed that children in the PDD group exhibited qualitatively and quantitatively different sleep patterns to nonautistic control children. CONCLUSIONS: The findings were discussed in light of current literature concerning circadian rhythm dysfunction, social difficulties, and abnormal melatonin levels in children with autism.

The sleep/wake rhythm in children with autism.

The sleep patterns of two groups of children with autism, one with moderate to severe intellectual handicap, and one with mild handicap to normal IQ level, were compared with those of children without autism. Parents completed 14 day sleep diaries and questionnaires. Results suggested that at some stage during childhood, particularly under 8 years of age, the majority of children with autism will experience sleep problems. These problems are likely to be severe in many cases and will generally include one or more of: extreme sleep latencies; lengthy periods of night waking, shortened night sleep; and early morning waking. Such problems may have some specificity for autism as they appear to be rare in non-handicapped children and in children with mild degrees of intellectual handicap. It is likely that sleep problems in early childhood are related to the severe social difficulties present in autism and the consequent inability of these children to use social cues to synchronize their sleep/wake cycle. Continued sleep difficulties at older ages and with higher IQ may also be related to arousal and anxiety factors.

Urinary cortisol circadian rhythm in a group of high-functioning children with autism.

Previous research has suggested that there may be dysfunction in the control of the hypothalamic-pituitary-adrenal axis in autistic children. Both an abnormal cortisol circadian rhythm and failure to suppress cortisol secretion in response to dexamethasone have been reported. This study investigated the basal urinary cortisol circadian rhythm in a group of high-functioning children with autism and matched controls. No evidence was found for abnormal temporal placement of the circadian rhythm in the autistic group. There was a tendency towards cortisol hypersecretion during the day, predominantly in those autistic children who were integrated into the normal school system. While the temporal parameters of the cortisol circadian rhythm in these children with autism were probably normal, the tendency towards cortisol hypersecretion may indicate an environmental stress response in this group.

Effect of excess intracranial amino acids on memory: a behavioural survey.

Nineteen naturally occurring amino acids were administered intracranially to day-old chicks at various times before and after a single trial passive avoidance learning task. The results suggest a consistent and simple difference between essential and non-essential amino acids. Except for arginine, phenylalanine, tryptophan and tyrosine, the essential amino acids had no effect on memory formation when administered 5 min before or immediately after learning. However, arginine, phenylalanine and tryptophan yielded amnesia after 60 min following learning, when given between 5 min before and 2.5 min after learning. In the case of tryptophan, amnesia was only temporary, lasting from 60 min to 240 min post-learning. All non-essential amino acids, when administered between 5 min before and 5 min after learning yielded amnesia by 60 min post-learning, with no evidence of recovery by 24 hr post-learning. Alanine-, asparagine-, cysteine- and glutamate-treated chicks, however, showed signs of generalized avoidance shortly after administration. The retention time courses after injection of glutamine, proline, serine and taurine were similar to that obtained with the non-metabolizable amino acid alpha-amino-isobutyric acid, and amnesia arising from administration of these amino acids was counteracted by diphenylhydantoin, as was amnesia induced by phenylalanine and tyrosine. The retention function obtained with tryptophan was similar to that obtained with 5-hydroxytryptamine, and DPH had no effect on the action of tryptophan or the actions of arginine, alanine or asparagine. The findings were interpreted in the context of a three-stage model of memory formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical aspects of protein synthesis inhibition by cycloheximide in one or both hemispheres of the chick brain.

Instracrnial administration of cycloheximide into one hemisphere of the chick brain resulted in inhibition of 14C-leucine incorporation into protein only in that hemisphere when the labelled amino acid was administered intracranially. With pericardial injections of labelled amino acid, inhibition of 14C-leucine incorporation was obtained in both the CXM-treated and the untreated hemisphere, when compared with bilateral saline-treated controls. The levels of inhibition were comparable to those obtained with bilateral administration of CXM. There was, however, a slight but significantly higher level of inhibition in the CXM-treated hemisphere. The results were interpreted as supporting the conclusion that monocular learning in chicks resulted in the formation of an engram only in the trained hemisphere.