Sleepless and Sleepy Children with Autistic Spectrum Disorders

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1 Sleepless and Sleepy Children with Autistic Spectrum Disorders Dr Paul Gringras Consultant in Paediatric Neurodisability Director Paediatric Sleep Clinic Paediatric Neurosciences Guys and St Thomas s NHS Foundation Trust

2 Topics Why children need sleep Measuring sleep and impact of poor sleep Sleep problems in Autism Some behavioural treatments Some medication treatments What happens to childhood sleep problems in adults

3 Why bother with sleep?

4 Slumber parties Impaired verbal creativity Specific working memory tasks Increased aggressive and social problems Even loss of one hours sleep per night

5 Impact of sleep problems: Physical Growth: disruption of normal growth hormone release during sleep Immune function: sleep deprivation impairs host defenses; infection induces somnogenic cytokines Endocrine system regulation: cortisol, prolactin thyroid Metabolic regulation: obesity/metabolic syndrome linked to sleep deprivation Injuries more common in sleepy children

6 Measuring sleep and its effects in children

7 Investigations Consider Paediatric sleep questionnaire Diary Home video Home actigraphy Home oximetry plus actigraphy PSG-still ideally home based

8 Why do children with autism sleep particularly badly? 20% of our referrals have autism (n=300) A range of sleep phenotypes Studies report sleep problems in 44-83% Sleep onset insomnia Sleep fragmentation REM Sleep Behaviour Disorders Parasomnias Sleep disordered breathing Circadian rhythm disorders Periodic limb movement disorder Melatonin ligand/receptor problems All have different causes, and require different interventions

9 Behavioral Sleep Disorders: Management Extinction: cry it out, limited parental acceptance but most effective Graduated extinction: Use of timed checks Scheduled awakenings Systematic desensitization for fears Preventative education for parents

10 Evidence for behavioural interventions >420 children in 4 studies that showed extinction or graduated extinction works Evidence in children with learning difficulties that an information booklet can be as effective as therapy In most studies, across most conditions, behavioural input achieves an effect size of >0.6 Mindell JA. J Pediatr Psychol Kuhn BR, Elliott AJ. J Psychosomatic Res Weiss 2005 ACAP conference proceedings Montgomery 2004 Child neurology and disability

11 Behavioural Interventions Are addressing behavioural components, not sleep physiology Interventions that actually change the child s sleep. Interventions that do not actually change the child s sleep, but result in the child no longer disrupting the parents Positive changes most likely if extinction used, with potential for temporary extreme deteriorations.

12 Response to behavioural interventions Usually Pre-sleep disruptions Falling asleep alone Disturbing night wakings Co-sleeping Rarely Sleep latency Sleep duration Early morning wakening Night rocking

13 Light, sleep phase and genes

14 Delayed sleep phase -listening to the children I m just not tired when they want me to go to bed I always work best at night when its dark Once I fall asleep I sleep really well I love a long sleep in on the weekend Holidays are fine

15 Sleep diary for at least two weeks Actigraphy for at least two weeks Delayed Sleep Phase Dim light melatonin onset measurement Diagnosis

16 Treatments No Naps! Anchor morning wake-up time Chronotherapy Light therapy Melatonin (phase advance, not as a soperific)

17 Paediatric non 24 hr PER3 This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain Within UK population:10% have a long version (lark) 45% have a short version (owl) 45% are a mixture

18 Paediatric non 24 hr ASMT ASMT encodes the last enzyme of melatonin synthesis and is often absent or mutated in ASD Low melatonin levels often reported in ASD however: Low melatonin not diagnostic of ASD direct role of melatonin on modulation of neuronal networks unknown Could explain the high prevalence of sleep disturbance in ASD

19 Genetics of melatonin Highly heritable Mutations in ASMT lead to low levels of melatonin and sleep disorders Increased in populations with learning disability and autism Enzyme synthesising genes TPH2, AA-NAT, ASMT Melatonin receptor genes MTNR1A, MTNR1B, GPR50 ASD and Learning Difficulty Genes NLGN, MAOA, MAOB, COMT, SLC6A4, GABAR Melke J, et al. Abnormal Melatonin Synthesis in Autism and Hyperactivity. Molecular Psychiatry 2007

20 Pre and post Treatment 6yr old girl with autistic spectrum disorder Presented with difficulties initiating and maintaining sleep Behavioural intervention and Melatonin (liquid 6mg) have improved sleep initiation? Awakenings still a problem

21 Survey of UK Melatonin Experience 142 respondents each with an average of eight children on melatonin Total number of children ~1900 Dose 0.5 mg-24 mg Maintenance 6-9mg (25-75 interquartile range) Age range 1-21 years 50% sleep onset problems, 10% sleep maintenance Most had tried sleep hygiene, antihistamines or chloral hydrate first -Gringras Waldron,Bramble,Gringras 2005

22 Presenting Disorder Percentage Autism ADHD LD Visual I

23 Clinical impression of response Never Rarely Usually Always Percentage

24 12 UK Centres and the Pasteur Institute 350 Children (200 Autism) 170 RCT melatonin 0.5mg-12mg Actigraphy and sleep diaries Daytime measures behaviour and cognition Salivary melatonin and DNA analysis

25 Contact: Southern centres :Northern centres Nottingham Liverpool Manchester Bristol Oxford Derby/ Chesterfield Birmingham London Guys and St Thomas/St Georges/Great Ormond Street/Royal Free hospital

26 Long-term outcomes

27 Why do people think sleep problems disappear? In conclusion our study indicates that objective sleep disturbances are still present in adolescents and young adults with autistic disorder or Asperger Syndrome, although sleep problems are less frequently reported by parents or caretakers after childhood. The main finding of the present study is that adults with ASD who do not have spontaneous sleep complaints nevertheless show subjectively and objectively measured sleep disturbance.

28 Study Ref Age Range (mean) Sleep Latency (mins) Total Sleep Time Sleep Efficiency (%) Night Wakings Elia Reduced by 1hr 15 minutes in ASD Diomedi (18) 81% ASD vs 92% controls 11.4 ASD vs 4.2 controls Oyane % Tani ASD vs 31 controls 84.4 ASD vs 91.5 controls Limoges years (21.1) vs ns

29 Medications that disrupt sleep Anticonvulsants Phenytoin/lamotrigine Beta-blockers SSRI Decongestants Antihistamines Corticosteroids Theophylline Sulfasalazine

30 Insomnia medications with poor evidence base in children Clonidine Tricyclics Trazodone Benzodiazepines Zolpidem/zopiclone Zalepon

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