Populations Students Early Career Families Educators View My Account
Skip Navigation LinksNASP Home Publications Communiqué Volume 42, Issue 6 Pediatric School Psychology

Pediatric School Psychology

Melatonin Imbalance and Sleep Dysfunction in Children With Autism

By Katelyn Rose & Paul C. MacCabe

Many children diagnosed with autism spectrum disorder (ASD) experience irregular sleep patterns, commonly in the form of delayed sleep onset, frequent nighttime wakings, and reduced sleep duration (Richdale & Schreck, 2009). Sleep problems occur in 40% to 80% of children with ASD, a significantly higher rate in comparison with 10% to 20% of typically developing children (Cortesi, Gianotti, Ivanenko, & Johnson, 2010). Because many children with autism cannot maintain sleep during the night, they can experience impaired alertness, behavioral issues, and exacerbation of autism symptoms during the daytime hours. High levels of parental stress as well as impaired parent–child relationships have also been associated with sleep disorders in children with ASD (Richdale & Schrek, 2009).

Current research suggests that the circadian rhythms, which are internally generated activity cycles based upon 24-hour intervals, seem to be abnormal in children diagnosed with autism. This disturbance in circadian rhythms in children with autism has been linked to irregular levels of melatonin, a neurohormone synthesized from serotonin and located in the pineal gland, with a key role in regulating sleep/wake patterns (Glickman, 2009). In individuals without sleep disorders and normally entrained to the light–dark cycle, melatonin hormone levels typically rise at night and return to baseline in the morning during daylight, with low concentrations throughout the day. In children with autism, research implicates diminished melatonin secretion, thereby affecting the biological tendency for sleepiness during the night and wakefulness during the light phase of day (Glickman, 2009).

Sleep irregularities are highly prevalent in children with autism spectrum disorder. In a study that assessed sleep disturbance in 69 children with ASD, patterns of sleeplessness were evaluated and analyzed (Wiggs & Stores, 2004). Information was gathered through parental reports, sleep diaries, and actigraphs (small, noninvasive sensors worn by each child for 5 nights). The researchers found that the most common issue related to sleeplessness stemmed from a behavioral basis (“that is, the children had not learnt appropriate ways, or had learnt inappropriate ways of getting to sleep or staying asleep” [p. 378]). The authors designated behavioral sleep problems as difficulty initiating sleep, stalling or refusing to go to bed, as well as complaints of sleeplessness. The second most common issue underlying reported sleeplessness was related to circadian sleep–wake problems, such as delayed sleep, the inability to fall asleep or wake at a desired time, and irregular sleep–wake patterns (i.e., sleeplessness or extreme sleepiness). However, a critique of this study is that the behavioral sleep issues that were mentioned may result from impaired circadian systems and/or irregular melatonin levels, yet this was not assessed. As children suffering from circadian abnormalities may feel wakeful at night and, conversely, tired during the day, they would be inclined to express this through their behavior (and children with autism have limited ability to verbally express their tiredness).

In one study, the role of melatonin was evaluated via blood samples of 14 children with autism in 4-hour intervals throughout a 24-hour cycle (Kulman et al., 2000). Blood samples were also measured in a control group of 20 typically developing, non-ASD children. The results indicated that controls presented an increase of melatonin during the night, with values at least three times greater than during the day. However, each of the blood samples of the autism sample showed no increase of melatonin during the nighttime, and there was little variability throughout the day. In fact, 4 of the 14 children had higher levels of melatonin during the day. Overall, the children with autism showed profound sleep disturbances in comparison to the control group, with sleep irregularities directly correlated to the presenting melatonin levels. The authors proposed that the pineal gland, the endocrine gland that produces melatonin, might be damaged in children with autism, thereby altering their circadian rhythms and yielding a deficiency in melatonin secretion.

Another study examined the association between melatonin and sleep difficulties in children with autism by testing melatonin levels as detected by the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM) through urine excretion (Leu et al., 2010). The study involved 23 children ages 4 to 10 diagnosed with ASD. Parents of the participants were given the Children's Sleep Habits Questionnaire (CSHQ) to screen the children for common pediatric sleep disorders such as bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night waking, parasomnias, sleep-disordered breathing, and daytime sleepiness. From the parental survey results, the researchers categorized 15 children as having moderate or severe sleep issues. Through the collection of their urine over one night, 6-SM excretion rates were assessed and overall, determined to be low in all participants of the study. The researchers found higher levels of 6-SM were associated with less daytime sleepiness as well as deeper phases of sleep. The researchers proposed that melatonin may promote deep sleep, and consistently low levels of melatonin would make the deeper phases of sleep harder to achieve, in turn creating a higher probability of sleep disturbance and sleeplessness (Leu et al., 2011). However, this study was limited in only providing correlational results, with a small sample size and only one urine sample, collected in the morning, rather than throughout the night during different periods of sleep.

In a study designed to examine the underlying cause of melatonin deficits in individuals with autism, the researchers investigated the ASMT (acetylserotonin methyltransferase) gene, which codes for the last ASMT enzyme involved in melatonin synthesis (Melke et al., 2008). The ASMT enzyme converts normelatonin to melatonin in the final reaction in melatonin biosynthesis. In the study, researchers collected blood samples from 250 participants with ASD and from a control group of 255 individuals. ASMT abnormalities and variations, such as splice-site mutations and abnormal transcripts were found in those with ASD, and not detected in the typically developing control group. ASMT activity and melatonin concentration were measured through blood platelets of 43 individuals with ASD and their parents as well as a control group of 48. A significantly lower degree of ASMT activity as well as decreased plasma melatonin levels was found in those with ASD and their parents when compared to the control group. Sleep patterns of autistic individuals with ASMT mutations and their parents were also assessed. The researchers concluded that these individuals displayed sleep abnormalities with no concomitant increase of melatonin during the night. Because variations in the ASMT gene as well as melatonin deficits were also identified in the typically developed parents of children with autism, the authors propose that these variations may have a genetic component and could potentially be considered a risk factor not only for circadian rhythm abnormalities leading to irregular sleep/wake patterns, but for ASD as well.

Rossignol and Frye (2011) conducted a review of the current research linking melatonin and autism spectrum disorders. Database searches including PubMED, Google Scholar, CINAHL, EMBASE, Scopus, and ERIC were used to identify the 35 studies that met criteria to be included in the review. Of the nine studies reviewed that measured concentrations of melatonin in individuals with ASD, all reported melatonin abnormalities. Seven of these studies found that there were lower concentrations of melatonin in this population when compared to a control group. Two studies reported higher concentrations of melatonin during the day. Four studies examined genes that code for melatonin receptors as well as enzymes that are involved in melatonin synthesis, and all four examined the ASMT gene. Each of these studies implicated abnormalities in the ASMT gene, ranging from ASMT mutations, duplications, and reduced enzymatic activity. The studies suggested that the abnormalities could contribute to lower melatonin concentrations in individuals with ASD. Numerous studies in the review involved melatonin interventions, and these studies showed significant improvements in sleep duration when the subjects were given supplemental melatonin.

Supplemental melatonin has been studied as a corrective intervention for sleep disturbance in ASD children. In one study, 24 children ages 3–10 and diagnosed with ASD completed an open-label, supplemental melatonin dose escalation study (Malow et al., 2012). The study assessed each child's response to increasing dosages of melatonin as it related to their existing sleep difficulties. The authors noted that the children's atypical sleep behavior may be exacerbating related symptoms of autism, including “social interactions, repetitive behaviors, affective problems, and inattention/hyperactivity” (p. 1729). The researchers proposed that supplemental melatonin may be effective in not only improving sleep outcomes and child and family health, but also in reducing autism symptoms. The children were initially given 1mg (4ml) of liquid melatonin for 3 weeks. If they did not respond satisfactorily to this dosage, defined as falling asleep within 30 minutes after administration 5 or more nights per week, the dosage was increased to 3mg for 3 weeks. Similarly, if the response was not satisfactory, clinicians intensified the dosage to 6mg for 3 weeks, and then 9mg for 3 weeks. Parents completed a battery of surveys before and after treatment to assess behavioral or emotional changes correlated with the intervention. These surveys included the Children's Sleep Habits Questionnaire (CSHQ), the Child Behavior Checklist, the Repetitive Behavior Scale-Revised, and the Parenting Stress Index Short Form. All children wore actigraphy devices to monitor their sleep and movement throughout the night. The results revealed that the majority of children, 21 out of the 24, responded satisfactorily to a 1mg or 3mg dosage of supplemental melatonin. All postintervention surveys completed by the parents showed a significant improvement in their child's sleep/wake patterns, daytime behavior, and overall affect as well as their own levels of parenting stress. A limitation of the study is the lack of a control or placebo group, in addition to small sample size.

In another melatonin intervention study, 25 children diagnosed with ASD, ages 2–10, were evaluated for abnormal sleep patterns through CSHQ and sleep diaries over a 2-year period (Giannotti, Cortesi, Cerquiglini, & Bernabei, 2006). The majority of the participants presented with sleep problems such as sleep onset delay, night waking, and poor sleep maintenance. Surveys and sleep diaries were solicited at baseline, and at the first, third, and sixth month of melatonin treatment, and 1 month after discontinuation of the treatment. At baseline, the participating children were each given 3mg of melatonin, but in subsequent follow-up visits, clinicians increased or decreased the dosage dependent upon the needs of each individual case. A month and a half after treatment, the intervention design was delivered for a second time to 16 children who returned to pretreatment sleep habits. All participants in the study were evaluated in 1- and 2-year follow-up visits. In both of these visits, the 16 children who maintained the melatonin treatment presented ongoing positive sleep patterns, while the 9 participants who did not extend treatment showed a regression to abnormal sleep behavior. A limitation of the study is that no melatonin samples were obtained from the participants throughout the intervention period (except at the follow-up visit), which would help to identify whether alterations in melatonin levels were due to the intervention or other developmental changes.

A recent comprehensive review of studies of melatonin in autism spectrum disorders indicated converging evidence of the role of melatonin in sleep disorders in ASD, but also noted the nonspecificity of these findings (Tordjman et al., 2013). That is, melatonin irregularities might not be unique to children with autism; while children with Down syndrome have been found to have normal melatonin levels, increased levels have been reported in individuals with Fragile X. Furthermore, Tordjman and colleagues (2013) reported that studies using melatonin supplements reported improvements in ASD symptoms including communication, social withdrawal, stereotyped behaviors and rigidity, and anxiety. Although several studies used dose escalation, no studies examined dose–response relationship for melatonin in ASD, and therefore it is unknown how much supplemental melatonin leads to positive behavioral effects. These studies were further hindered by heterogeneous samples and broad age ranges including prepubertal, pubertal, and postpubertal children, which “… is a problem given that pineal melatonin secretion is influenced by age and pubertal stage” (p. 20525). Nevertheless, the authors conclude that restoring regular physiological rhythms, including circadian rhythms, through small doses of melatonin could help restore the synchronization of internal biological clocks and correct the “… internal asynchrony that causes children with autism to feel permanently 'out of sync' with other people” (p. 20531).

The current research on melatonin levels and sleep in children with autism provides strong evidence for a correlation between irregular melatonin levels and erratic sleep behavior. Research suggests that a lack of melatonin disrupts one's biological circadian rhythms, causing a broad range of sleep disturbances. The foundation for melatonin abnormalities in autistic children remains unproven, but leading theories hypothesize that they stem from pineal gland dysfunction or ASMT gene defects. Additional research is needed that examines not only diagnostic syndromes but also specific behaviors and subtype-specific characteristics to elucidate the nonspecificity melatonin findings of ASD. Interventions that employ supplemental melatonin as a treatment option for sleep disturbance have produced positive results. Moreover, supplemental melatonin is considered to produce minimal side effects and since it is a biological complement, is largely viewed as safe (Doyen et al., 2011).

Implications for School Psychologists

Many children who face the challenges of autism also experience sleep disorders. School psychologists may take a lead role in working with these children, their families, and teachers, as well as the school system, to address the needs of this population. Within the school setting, school psychologists are in a unique position to spread awareness about ASD, sleep disorders, and the symptomatology produced from this interaction. It has been found that children diagnosed with ASD who suffer from sleep disorders may experience impaired cognitive abilities as well as low adaptive skills. Specifically, affected children may exhibit a decline in perceptual and verbal abilities as well as skill deficits in typical daily living tasks such as eating, toileting, and practicing good hygiene (Taylor, Schreck, & Mulick, 2012). A lack of appropriate social skills as well as an increase in stereotypic behavior and heightened emotional symptoms have also been linked to sleep difficulties in children with ASD (Vriend, Corkum, Moon, & Smith, 2011). These skills are essential for healthy functioning in a school environment.

To most effectively help children with ASD who face sleep problems, it is essential that school psychologists become aware of the difficulties that these children may be experiencing in the classroom. Teachers interact with their students on a daily basis and can assist in identifying telltale signs of excessive sleepiness in children with ASD. With consistent teacher feedback, school psychologists can efficiently screen students for sleep problems and provide needed support. Furthermore, ongoing school psychologist/ teacher collaboration is important in furthering each professional's understanding of the issue and actively taking part in its management (Everhart, 2011).

To help the school psychologist better understand each child's specific sleep schedule and habits, a recorded account or sleep diary, which consists of the child's sleep and wake times as well as other pertinent data, can be organized by the child's parents and provides valuable information on the overall quality and duration of sleep (Buckhalt, Wolfson, & El-Sheikh, 2009). Sleep-related questionnaires, such as the BEARS sleep screening tool, the Children's Sleep Habits Questionnaire (CSHQ), and the Epworth Sleepiness Scale (ESS) are useful assessment measures that school psychologists can utilize to obtain a comprehensive developmental history (Everhart, 2011). Interviews with the parents and child, if appropriate, can also reveal more specific information about the particular sleep problem and its course.

Psychological and behavioral interventions will vary depending on individual manifestations of sleep dysfunctions. Sleep problems often persist from early childhood throughout adolescence, but the nature of the sleep disorder may change as one ages. Young children diagnosed with ASD regularly present behaviors associated with sleep anxiety, bedtime resistance, and parasomnias, while adolescents with ASD frequently experience insomnia (Goldman, Richdale, Clemons, & Malow, 2012). Behavior modification strategies, parent education, and medication are interventions commonly used among elementary-age school children, whereas cognitive–behavioral therapy and emphasis on relaxation techniques may be more appropriate for adolescents who suffer from sleep disorders (Buckhalt et al., 2009). These strategies will likely need to be adapted for use with children with ASD, based on the child's skill level and symptom severity. School psychologists should provide routine guidance to all students for practicing positive sleep habits and healthy sleep hygiene (Everhart, 2011).

When administering diagnostic assessments, the school psychologist must account for the daily amount of sleep the child has had in order to gauge whether sleepiness may be contributing to low test scores. In addition, tests should be administered at an optimal time of day for the child, when he or she is less likely to be tired. Additional accommodations such as providing extended time, allowing frequent breaks, or administering the test over a number of days may be necessary. Retesting the student after treatment of the sleep disorder may be helpful in providing evidence for the relationship between sleep and cognitive performance (Buckhalt et al., 2009). School psychologists should follow the most recent research on sleep disorders in the ASD population, and maintain communication with the child's primary care physician or sleep specialists who are treating the child with melatonin supplements. This can help ensure that dosage changes are carefully monitored and healthcare providers are given accurate assessments of school-based behavior to best inform the treatment regimen.

School psychologists can also organize school-wide or district-wide reforms that help students with sleep disorders. One such reform might be advocating for later bus routes or delayed school start times. Research shows that students with an insufficient amount of sleep, specifically less than 8 hours, show more daytime tiredness and behavior problems, lower academic achievement, and more negative self-concept and attitude toward life compared to peers who receive more sleep. Later start times, as modest as a 20-minute postponement, may lengthen nighttime sleep duration and produce more positive student behavior during the school day (Perkinson-Gloor, Lemola, & Grob, 2013). Since many children with autism exhibit irregular melatonin levels with disproportionate elevations during the day rather than night (Glickman, 2009), this group may particularly benefit from extended morning sleep before the school day begins.

Sleep takes place in the home, and while school psychologists may be able to offer assistance during school hours, the role of parents is essential for managing nighttime behavior and ongoing sleep programs. Parents should be instructed in the use of extinction to ignore all bedtime disruptions until morning, which has proven effective in regulating bedtime routines and limiting negative behavior. Parents can also use scheduled awakenings, which have been shown to increase overall sleep time and reduce parasomnias (Vriend et al., 2011). School psychologists can collaborate with parents to develop a plan for healthy sleep habits and provide the therapeutic tools needed to ameliorate sleep difficulties.

School psychologists can serve an important role in the education and management of children with ASD by identifying and treating a commonly overlooked symptom of the disorder, sleep disturbance. Sleep disturbances are often not considered when assessing the functioning of children with ASD, yet this basic biological function serves as an important setting event for how the child will behave and function during the ensuing school day. Treatment of sleep disturbances can significantly reduce emotional and behavioral disruptions and improve cognitive and academic functioning, and as such should be considered as a first-line intervention.

References

Buckhalt, J., Wolfson, A., & El-Sheikh, M. (2009). Children's sleep and school psychology practice. School Psychology Quarterly, 24(1), 60–69. doi:10.1037/a0014497

Cortesi, F., Giannotti, F., Ivanenko, A., & Johnson, K. (2010). Sleep in children with autistic spectrum disorder. Sleep Medicine, 11(7), 659–664. doi:http://dx.doi.org/10.1016/ j.sleep.2010.01.010

Doyen, C., Mighui, D., Kaye, K., Colineaux, C., Beaumanoir, C., Mouraeff, Y., …Contejean, Y. (2011). Melatonin in children with autism spectrum disorders: Recent and practical data. European Child and Adolescent Psychiatry, 20, 231–239. doi:10.1007/s00787-011-0162-8

Everhart, D. (2011). Sleep disorders in children: Collaboration for school-based intervention. Journal of Educational and Psychological Consultation, 21, 133–148. doi:10.1080/10474412 .2011.571521

Giannotti, F., Cortesi, F., Cerquiglini, A., & Bernabei, P. (2006). An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism. Journal of Autism and Developmental Disorders, 36(6), 741–752. doi:10.1007/ s10803-006-0116-z

Glickman, G. (2010). Circadian rhythms and sleep in children with autism. Neuroscience and Biobehavioral Reviews, 34(5), 755–768. doi:http://dx.doi.org/10.1016/j.neubiorev. 2009.11.017

Goldman, S., Richdale, A., Clemons, T., & Malow, B. (2012). Parental sleep concerns in autism spectrum disorders: Variations from childhood to adolescence. Journal of Autism and Developmental Disorders, 42, 531538. doi: 10.1007/s10803-011-1270-5

Kulman, G., Lissoni, P., Rovelli, R., Roselli, M., Brivio, F., & Sequeri, P. (2000). Evidence of pineal endocrine hypofunction in autistic children. Neuroendocrinology Letters, 20, 31– 34. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11455326

Leu, R., Beyderman, L., Botzolakis, E., Surdyka, K., Wang, L., & Malow, B. (2011). Relation of melatonin to sleep architecture in children with autism. Journal of Autism and Developmental Disorders, 41(4), 427–433. doi:10.1007/ s10803-010-1072-1

Malow, B., Adkins, K., McGrew, S., Wang, L., Goldman, S., Fawkes, D., & Burnette, C. (2012). Melatonin for sleep in children with autism: A controlled trial examining dose, tolerability, and outcomes. Journal of Autism and Developmental Disorders, 42(8), 1729– 1737. doi:10.1007/s10803-011-1418-3

Melke, J., Botros, H., Chaste, P., Betancur, C., Nygren, G., Anckarsater, H., … Bourgeron, T. (2008). Abnormal melatonin synthesis in autism spectrum disorders. Molecular Psychiatry, 13(1), 90–98. doi:10.1038/sj.mp.4002016

Perkinson-Gloor, N., Lemola, S., & Grob, A. (2013). Sleep duration, positive attitude toward life, and academic achievement: The role of daytime tiredness, behavioral persistence, and school start times. Journal of Adolescence, 36(2), 311–318. doi:0.1016/ j.adolescence.2012.11.008

Richdale, A., & Schreck, K. (2009). Sleep problems in autism spectrum disorders: Prevalence, nature, & possible biopsychosocial aetiologies. Sleep Medicine Reviews, 13(6), 403–411. doi:http://dx.doi.org.ez-proxy.brooklyn.cuny.edu:2048/10.1016/j.smrv.2009.02.003

Rossignol, D., & Frye, R. (2011). Melatonin in autism spectrum disorders: A systematic review and meta-analysis. Developmental Medicine and Child Neurology, 53(9), 783–792. doi:10.1111/j.1469-8749.2011.03980.x

Taylor, M., Schreck, K., & Mulick, J. (2012). Sleep disruption as a correlate to cognitive and adaptive behavior problems in autism spectrum disorders. Research in Developmental Disabilities, 33(5), 1408–1417. doi:10.1016/ j.ridd.2012.03.013

Tordjman, S., Najjar, I., Bellisant, E., Anderson, G. M., Barburoth, M., Cohen, D., … Vernay- Leconte, J. (2013). Advances in the research of melatonin in autism spectrum disorders: Literature review and new perspectives. International Journal of Molecular Sciences, 14, 20508–20542. doi:10.3390/ijms141020508

Vriend, J., Corkum, P., Moon, E., & Smith, I. (2011). Behavioral interventions for sleep problems in children with autism spectrum disorders: Current findings and future directions. Journal of Pediatric Psychology, 36(9), 1017–1029. doi:10.1093/jpepsy/jsr044

Wiggs, L., & Stores, G. (2004). Sleep patterns and sleep disorders in children with autistic spectrum disorders: Insights using parent report and actigraphy. Developmental Medicine and Child Neurology, 46(6), 372–380.


Katelyn Rose is a graduate student in the school psychologist graduate program at Brooklyn College of the City University of New York (CUNY). Paul C. McCabe, PhD, NCSP, is professor and program coordinator in the school psychologist graduate program at Brooklyn College – CUNY, Brooklyn, NY, and a contributing editor to Communiqué.