***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: A high prevalence of subjective insomnia in adults with Asperger syndrome has been reported . In the present study the sleep quality of these patients was studied using wrist actigraphy .  Nineteen adults with Asperger syndrome and frequent feelings of insomnia were compared with 10 controls devoid of neuropsychiatric disorders and subjective sleep problems during six consecutive nights . The patients had similar actigraphic sleep profile to the controls . The subjective low sleep quality in patients was not reflected in actigraphic assessment of sleep . This finding suggests that pervasive anxiety inherent in persons with Asperger syndrome predisposes them to insomnia complaints Although melatonin and cognitive-behavioural therapy have shown efficacy in treating sleep disorders in children with autism spectrum disorders , little is known about their relative or combined efficacy . One hundred and sixty children with autism spectrum disorders , aged 4 - 10 years , suffering from sleep onset insomnia and impaired sleep maintenance , were assigned r and omly to either ( 1 ) combination of controlled-release melatonin and cognitive-behavioural therapy ; ( 2 ) controlled-release melatonin ; ( 3 ) four sessions of cognitive-behavioural therapy ; or ( 4 ) placebo drug treatment condition for 12 weeks in a 1 : 1 : 1 : 1 ratio . Children were studied at baseline and after 12 weeks of treatment . Treatment response was assessed with 1-week actigraphic monitoring , sleep diary and sleep question naire . Main outcome measures , derived actigraphically , were sleep latency , total sleep time , wake after sleep onset and number of awakenings . The active treatment groups all result ed in improvements across all outcome measures , with moderate-to-large effect sizes from baseline to a 12-week assessment . Melatonin treatment was mainly effective in reducing insomnia symptoms , while cognitive-behavioural therapy had a light positive impact mainly on sleep latency , suggesting that some behavioural aspects might play a role in determining initial insomnia . The combination treatment group showed a trend to outperform other active treatment groups , with fewer dropouts and a greater proportion of treatment responders achieving clinical ly significant changes ( 63.38 % normative sleep efficiency criterion of > 85 % and 84.62 % , sleep onset latency < 30 min ) . This study demonstrates that adding behavioural intervention to melatonin treatment seems to result in a better treatment response , at least in the short term BACKGROUND Many studies in autistic disorder report sleep problems and altered circadian rhythms , suggesting abnormalities in melatonin physiology . Additionally , melatonin , a pineal gl and hormone produced from serotonin , is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology . METHODS Nocturnal urinary excretion of 6-sulphatoxymelatonin was measured by radioimmunoassay in groups of children and adolescents with autistic disorder ( n = 49 ) and normal control individuals ( n = 88 ) matched on age , sex , and Tanner stage of puberty . RESULTS Nocturnal 6-sulphatoxymelatonin excretion rate was significantly and substantially lower in patients with autism than in normal controls ( mean + /- SEM , .75 + /- .11 vs. 1.80 + /- .17 microg/hr , p = .0001 ) , and was significantly negatively correlated with severity of autistic impairments in verbal communication and play ( p < .05 ) . CONCLUSIONS These findings indicate clearly that nocturnal production of melatonin is reduced in autism . Further research is warranted in order to underst and the mechanisms underlying the lower melatonin production , to assess the impact of altered melatonin on the pathophysiology and behavioral expression of autistic disorder , and to determine the utility of melatonin administration in individuals with autism STUDY OBJECTIVES ( 1 ) Compare sleep behaviors of children with autism spectrum disorders ( ASD ) with sleep behaviors of typically developing ( TD ) children using the Children 's Sleep Habits Question naire ( CSHQ ) ; ( 2 ) compare sleep quality --defined as mean activity , sleep latency , number of awakenings , sleep efficiency and total sleep time -- of the cohort of children with ASD and TD , as measured by 10 nights of actigraphy ; and ( 3 ) estimate the prevalence of sleep disturbances in the ASD and TD cohorts . DESIGN Descriptive cross-sectional study . SETTING The Children 's Hospital of Philadelphia . PARTICIPANTS R and omly selected children from the Regional Autism Center . The ASD cohort of 59 children , aged 4 to 10 years , ( 26 with autism , 21 with pervasive developmental disorder-not otherwise specified [ PDD-NOS ] , and 12 with Asperger disorder ) were compared with 40 TD control subjects . MEASUREMENTS AND RESULTS The  CSHQ  ,  sleep diaries  , and 10 nights of actigraphy  using the Sadeh algorithm of children with ASD and TD control subjects were compared . CSHQ showed 66.1 % of parents of children with ASD ( 62.5 % autism , 76.2 % PDD-NOS , 58.3 % Asperger disorder ) and 45 % of parents of the control subjects reported that their children had sleep problems . Actigraphic data showed that 66.7 % of children with ASD ( 75 % autism , 52.4 % PDD-NOS , 75 % Asperger disorder ) and 45.9 % of the control subjects had disturbed sleep . CONCLUSIONS The prevalence estimate of 45 % for mild sleep disturbances in the TD cohort highlights pediatric sleep debt as a public health problem of concern . The prevalence estimate of 66 % for moderate sleep disturbances in the ASD cohort underscores the significant sleep problems that the families of these children face . The predominant sleep disorders in the ASD cohort were behavioral insomnia sleep-onset type and insomnia due to PDD Asperger syndrome ( AS ) is a neurodevelopmental disorder belonging to autism spectrum disorders . Both children and adults with AS have subjective impairment in the initiation and continuity of sleep , and studies using objective assessment are sparse . Twenty young AS adults with frequent complaints of low sleep quality  were compared to 10 age- , gender- and education-matched controls without sleep complaints using polysomnography and spectral power analysis of slow-wave sleep . AS subjects displayed a similar polysomnographic profile as compared with controls . In spectral power analysis , a statistically nonsignificant trend towards decreased relative delta power and increased theta power in slow-wave sleep was found in the AS group . It seems that nonorganic insomnia , due to anxiety inherent in AS , is responsible for the low sleep quality in these subjects Background Sleep difficulties are prevalent in children with autism spectrum disorder ( ASD ) . The temporal nature of the association between sleep problems and ASD is unclear because longitudinal studies are lacking . Our aim is to clarify whether sleep problems precede and worsen autistic traits and ASD or occur as a consequence of the disorder . Methods Repeated sleep measures were available at 1.5 , 3 , 6 , and 9 years of age in 5151 children participating in the Generation R Study , a large prospect i ve birth cohort in the Netherl and s. Autistic traits were determined with the Pervasive Developmental Problems score ( PDP ) of the Child Behavior Checklist ( CBCL ) at 1.5 and 3 years and the Social Responsiveness Scale ( SRS ) at 6 years . This cohort included 81 children diagnosed with ASD . Results Sleep problems in early childhood were prospect ively associated with a higher SRS score , but not when correcting for baseline PDP score . By contrast , a higher SRS score and an ASD diagnosis were associated with more sleep problems at later ages , even when adjusting for baseline sleep problems . Likewise , a trajectory of increasing sleep problems was associated with ASD . Conclusions Sleep problems and ASD are not bidirectionally associated . Sleep problems do not precede and worsen autistic behavior but rather co-occur with autistic traits in early childhood . Over time , children with ASD have an increase in sleep problems , whereas typically developing children have a decrease in sleep problems . Our findings suggest that sleep problems are part of the construct ASD We describe our experience in using melatonin to treat  insomnia  , a common sleep concern , in children with autism spectrum disorders . One hundred seven children ( 2—18 years of age ) with a confirmed diagnosis of autism spectrum disorders who received melatonin were identified by review ing the electronic medical records of a single pediatrician . All parents were counseled on sleep hygiene techniques . Clinical response to melatonin , based on parental report , was categorized as ( 1 ) sleep no longer a concern , ( 2 ) improved sleep but continued parental concerns , ( 3 ) sleep continues to be a major concern , and ( 4 ) worsened sleep . The melatonin dose varied from 0.75 to 6 mg . After initiation of melatonin , parents of 27 children ( 25 % ) no longer reported sleep concerns at follow-up visits . Parents of 64 children ( 60 % ) reported improved sleep , although continued to have concerns regarding sleep . Parents of 14 children ( 13 % ) continued to report sleep problems as a major concern , with only 1 child having worse sleep after starting melatonin ( 1 % ) , and 1 child having undetermined response ( 1 % ) . Only 3 children had mild side-effects after starting melatonin , which included morning sleepiness and increased enuresis . There was no reported increase in seizures after starting melatonin in children with pre-existing epilepsy and no new-onset seizures . The majority of children were taking psychotropic medications . Melatonin appears to be a safe and well-tolerated treatment for insomnia in children with autism spectrum disorders . Controlled trials to determine efficacy appear warranted The purpose of this study was to determine the efficacy of controlled-release ( CR ) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders . A r and omized double-blind , placebo-controlled crossover trial of CR melatonin ( 5 mg ) followed by a 3-month open-label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects . Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs . Clinician rating of severity of the sleep disorder and improvement from baseline , along with caregiver ratings of global functioning and family stress were also obtained . Fifty-one children ( age range 2 - 18 years ) who did not respond to sleep hygiene intervention were enrolled . Fifty patients completed the crossover trial and 47 completed the open-label phase . Recordings of total night-time sleep and sleep latency showed significant improvement of approximately 30 min . Similarly , significant improvement was observed in clinician and parent ratings . There was additional improvement in the open-label somnolog measures of sleep efficiency and the longest sleep episode in the open-label phase . Overall , the therapy improved the sleep of 47 children and was effective in reducing family stress .  Children with neurodevelopmental disabilities , who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance  , showed improvement in melatonin therapy Objective To investigate longitudinal sleep patterns in children with autistic spectrum disorders ( ASDs ) . Study design Prospect i ve longitudinal study using Avon Longitudinal Study of Parents and Children , an English cohort born in 1991–1992 . Parental reports of sleep duration were collected by question naires at 8 time points from 6 months to 11 years . Children with an ASD diagnosis at age 11 years ( n=73 ) were identified from health and education records . Results From aged 30 months to 11 years old , children with ASD slept for 17–43 min less each day than contemporary controls . No significant difference in total sleep duration was found in infancy , but from 30 months of age children with ASD slept less than their peers , a difference that remained significant after adjusting for sex , ethnicity , high parity and epilepsy . The reduction in total sleep was wholly due to changes in night rather than daytime sleep duration . Night-time sleep duration was shortened by later bedtimes and earlier waking times . Frequent waking ( 3 or more times a night ) was also evident among the children with ASD from 30 months of age . Age-specific decreases of > 1SD within individuals in sleep duration across adjacent time points was a predictor of ASD between 18 months and 30 months of age ( p=0.04 ) and from 30 months to 42 months ( p=0.02 ) . Conclusions Sleep duration in children with ASD is reduced from 30 months of age and persists until adolescence Supplemental melatonin has shown promise in treating  sleep onset insomnia in children with autism spectrum disorders ( ASD ) . Twenty-four children , free of psychotropic medications , completed an open-label dose-escalation study to assess dose – response , tolerability , safety , feasibility of collecting actigraphy data , and ability of outcome measures to detect change during a 14-week intervention . Supplemental melatonin improved sleep latency , as measured by actigraphy , in most children at 1 or 3 mg dosages . It was effective in week 1 of treatment , maintained effects over several months , was well tolerated and safe , and showed improvement in sleep , behavior , and parenting stress . Our findings contribute to the growing literature on supplemental melatonin for insomnia in ASD and inform planning for a large r and omized trial in this population Sleep disturbances are common in patients with Asperger disorder . Although these sleep problems are often persistent and may significantly impair the child 's daytime well-being , no treatment studies have been reported . In this open clinical trial , the effectiveness of melatonin was studied in a sample of 15 children with Asperger disorder ( 13 boys , 2 girls ) aged 6 - 
    Output:
    
Our findings suggested that autistic subjects frequently present sleep disturbances in particular short sleep duration , low sleep quality /efficiency , and circadian sleep desynchronization such as delayed phases and /or eveningness .
Sleep disturbances and circadian sleep alterations have been related to the severity of autistic symptoms .
Genetic studies have shown polymorphisms in circadian CLOCK genes and in genes involved in melatonin pathways in subjects with ASD .
Conclusions : Sleep disturbances and circadian sleep alterations are frequent in subjects with autistic symptoms .
These subjects have shown polymorphisms in clock genes expression and in genes involved in melatonin production .
The impairment of circadian sleep regulation may increase the individual 's vulnerability to develop symptoms of ASD by altering the sleep regulation in toto , which plays a key role in normal brain development .
Even though controversies and " research gaps " are present in literature at this point , we may hypothesize a bidirectional relation between circadian sleep dysfunction and ASD .
In particular , circadian sleep dysrhythmicity may predispose to develop ASD symptoms and vice versa within a self-reinforcing feedback loop .
By targeting sleep disturbances and circadian sleep dysrhythmicity , we may improve treatment strategies for both children and adults with ASD