Skip to main content
SpringerLink
Log in

Relation of Melatonin to Sleep Architecture in Children with Autism

  • Original Paper
  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

Children with autism often suffer from sleep disturbances, and compared to age-matched controls, have decreased melatonin levels, as indicated by urine levels of the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM). We therefore investigated the relationship between 6-SM levels and sleep architecture in children with autism spectrum disorders (ASD). Twenty-three children, aged 4–10 years, completed two nights of polysomnography and one overnight urine collection for measurement of urinary 6-SM excretion rate. Parents completed the Children’s Sleep Habits Questionnaire. We found that higher urinary 6-SM excretion rates were associated with increased N3 sleep, decreased N2 sleep, and decreased daytime sleepiness. The results warrant further examination to examine the effects of supplemental melatonin on sleep architecture and daytime sleepiness.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Allik, H., Larsson, J. O., & Smedje, H. (2006). Insomnia in school-age children with Asperger syndrome or high-functioning autism. BMC Psychiatry, 6, 18.

    Article  PubMed  Google Scholar 

  • American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders, 4th edition. text revision. Washington, DC: American Psychiatric Association.

    Book  Google Scholar 

  • Andersen, I. M., Kaczmarska, J., McGrew, S. G., & Malow, B. A. (2008). Melatonin for insomnia in children with autism spectrum disorders. Journal of Child Neurology, 23(5), 482–485.

    Article  PubMed  Google Scholar 

  • Autism and Developmental Disabilities Monitoring Network, United States, 2006. (2009). Prevalence of autism spectrum disorders. MMWR Surveillance Summaries, 58(1), 57–66.

    Google Scholar 

  • Beck-Friis, J., von Rosen, D., Kjellman, B. F., Ljunggren, J. G., & Wetterberg, L. (1984). Melatonin in relation to body measures, sex, age, season and the use of drugs in patients with major affective disorders and healthy subjects. Psychoneuroendocrinology, 9(3), 61–277.

    Article  Google Scholar 

  • Bojkowski, C. J., & Arendt, J. (1988). Annual changes in 6-sulphatoxymelatonin excretion in man. Acta Endocrinologica, 117(4), 470–476.

    PubMed  Google Scholar 

  • Brzezinski, A., Vangel, M. G., Wurtman, R. J., Norrie, G., Zhdanova, I., Ben-Shushan, A., et al. (2005). Effects of exogenous melatonin on sleep: A meta-analysis. Sleep Medicine Reviews, 9(1), 41–50.

    Article  PubMed  Google Scholar 

  • Cagnacci, A. (1996). Melatonin in relation to physiology in adult humans. Journal of Pineal Research, 21(4), 200–213.

    Article  PubMed  Google Scholar 

  • Cardinali, D. P., & Pevet, P. (1998). Basic aspects of melatonin action. Sleep Medicine Reviews, 2(3), 175–190.

    Article  PubMed  Google Scholar 

  • Chamberlain, R. S., & Herman, B. H. (1990). A novel biochemical model linking dysfunctions in brain melatonin, proopiomelanocortin peptides, and serotonin in autism. Biological Psychiatry, 28(9), 773–793.

    Article  PubMed  Google Scholar 

  • Champier, J., Claustrat, B., Besancon, R., Eymin, C., Killer, C., Jouvet, A., et al. (1997). Evidence for tryptophan hydroxylase and hydroxy-indol-O-methyl-transferase mRNAs in human blood platelets. Life Sciences, 60(24), 2191–2197.

    Article  PubMed  Google Scholar 

  • Conti, A., Conconi, S., Hertens, E., Skwarlo-Sonta, K., Markowska, M., & Maestroni, J. M. (2000). Evidence for melatonin synthesis in mouse and human bone marrow cells. Journal of Pineal Research, 28(4), 193–202.

    Article  PubMed  Google Scholar 

  • Couturier, J. L., Speechley, K. N., Steele, M., Norman, R., Stringer, B., & Nicolson, R. (2005). Parental perception of sleep problems in children of normal intelligence with pervasive developmental disorders: Prevalence, severity, and pattern. Journal of the American Academy of Child and Adolescent Psychiatry, 44(8), 815–822.

    Article  PubMed  Google Scholar 

  • Garstang, J., & Wallis, M. (2006). Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child: Care, Health and Development, 32(5), 585–589.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Goldman, S. E., Surdyka, K., Cuevas, R., Adkins, K., Wang, L., & Malow, B. A. (2009). Defining the sleep phenotype in children with autism. Developmental Neuropsychology, 34(5), 560–573.

    Article  PubMed  Google Scholar 

  • Goodlin-Jones, B. L., Sitnick, S. L., Tang, K., Liu, J., & Anders, T. F. (2008a). The children’s sleep habits questionnaire in toddlers and preschool children. Journal of Developmental and Behavioral Pediatrics, 29(2), 82–88.

    Article  PubMed  Google Scholar 

  • Goodlin-Jones, B. L., Tang, K., Liu, J., & Anders, T. F. (2008b). Sleep patterns in preschool-age children with autism, developmental delay, and typical development. Journal of the American Academy of Child and Adolescent Psychiatry, 47(8), 930–938.

    PubMed  Google Scholar 

  • Graham, C., Cook, M. R., Kavet, R., Sastre, A., & Smith, D. K. (1998). Prediction of nocturnal plasma melatonin from morning urinary measures. Journal of Pineal Research, 24(4), 230–238.

    Article  PubMed  Google Scholar 

  • Honomichl, R. D., Goodlin-Jones, B. L., Burnham, M., Gaylor, E., & Anders, T. F. (2002). Sleep patterns of children with pervasive developmental disorders. Journal of Autism and Developmental Disorders, 32(6), 553–561.

    Article  PubMed  Google Scholar 

  • Iber, C., Ancoli-Israel, S., Chesson, A. L., Quan, S. F., & for the American Academy of Sleep Medicine. (2007). The AASM manual for scoring of sleep and associated events: Rules, terminology and technical specification (1st ed.). Westchester, IL: American Academy of Sleep Medicine.

    Google Scholar 

  • Jan, J. E., Hamilton, D., Seward, N., Fast, D. K., Freeman, R. D., & Laudon, M. (2000). Clinical trials of controlled-release melatonin in children with sleep-wake cycle disorders. Journal of Pineal Research, 29(1), 34–39.

    Article  PubMed  Google Scholar 

  • Kauppila, A., Kivela, A., Pakarinen, A., & Vakkuri, O. (1987). Inverse seasonal relationship between melatonin and ovarian activity in humans in a region with a strong seasonal contrast in luminosity. The Journal of Clinical Endocrinology and Metabolism, 65(5), 823–828.

    Article  PubMed  Google Scholar 

  • Kulman, G., Lissoni, P., Rovelli, F., Roselli, M. G., Brivio, F., & Sequeri, P. (2000). Evidence of pineal endocrine hypofunction in autistic children. Neuroendocrinology Letters, 21(1), 31–34.

    PubMed  Google Scholar 

  • Luboshitzky, R., Yanai, D., Shen-Orr, Z., Israeli, E., Herer, P., & Lavie, P. (1998). Daily and seasonal variations in the concentration of melatonin in the human pineal gland. Brain Research Bulletin, 47(3), 271–276.

    Article  PubMed  Google Scholar 

  • Malow, B. A. (2004). Sleep disorders, epilepsy, and autism. Mental Retardation and Developmental Disabilities Research Reviews, 10(2), 122–125.

    Article  PubMed  Google Scholar 

  • Malow, B. A., Marzec, M. L., McGrew, S. G., Wang, L., Henderson, L. M., & Stone, W. L. (2006). Characterizing sleep in children with autism spectrum disorders: A multidimensional approach. Sleep, 29(12), 1563–1571.

    PubMed  Google Scholar 

  • McGrew, S., Malow, B. A., Henderson, L., Wang, L., Song, Y., & Stone, W. L. (2007). Developmental and behavioral questionnaire for autism spectrum disorders. Pediatric Neurology, 37(2), 108–116.

    Article  PubMed  Google Scholar 

  • Melke, J., Goubran Botros, H., Chaste, P., Betancur, C., Nygren, G., Anckarsater, H., et al. (2008). Abnormal melatonin synthesis in autism spectrum disorders. Molecular Psychiatry, 13(1), 90–98.

    Article  PubMed  Google Scholar 

  • Nir, I., Meir, D., Zilber, N., Knobler, H., Hadjez, J., & Lerner, Y. (1995). Brief report: Circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism. Journal of Autism and Developmental Disorders, 25(6), 641–654.

    Article  PubMed  Google Scholar 

  • Nowak, R., McMillen, I. C., Redman, J., & Short, R. V. (1987). The correlation between serum and salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates: Two non-invasive techniques for monitoring human circadian rhythmicity. Clinical Endocrinology (Oxford), 27(4), 445–452.

    Article  Google Scholar 

  • Owens, J. A., Spirito, A., & McGuinn, M. (2000). The children’s sleep habits questionnaire (CSHQ): Psychometric properties of a survey instrument for school-aged children. Sleep, 23(8), 1043–1051.

    PubMed  Google Scholar 

  • Paavonen, E. J., Nieminen-von Wendt, T., Vanhala, R., Aronen, E. T., & von Wendt, L. (2003). Effectiveness of melatonin in the treatment of sleep disturbances in children with Asperger disorder. Journal of Child and Adolescent Psychopharmacology, 13(1), 83–95.

    Article  PubMed  Google Scholar 

  • Richdale, A. L. (1999). Sleep problems in autism: Prevalence, cause, and intervention. Developmental Medicine and Child Neurology, 41(1), 60–66.

    Article  PubMed  Google Scholar 

  • Ronnberg, L., Kauppila, A., Leppaluoto, J., Martikainen, H., & Vakkuri, O. (1990). Circadian and seasonal variation in human preovulatory follicular fluid melatonin concentration. The Journal of Clinical Endocrinology and Metabolism, 71(2), 492–496.

    Article  PubMed  Google Scholar 

  • Schreck, K. A., Mulick, J. A., & Smith, A. F. (2004). Sleep problems as possible predictors of intensified symptoms of autism. Research in Developmental Disabilities, 25(1), 57–66.

    Article  PubMed  Google Scholar 

  • Sivan, Y., Laudon, M., Tauman, R., & Zisapel, N. (2001). Melatonin production in healthy infants: Evidence for seasonal variations. Pediatric Research, 49(1), 63–68.

    Article  PubMed  Google Scholar 

  • Slominski, A., Tobin, D. J., Zmijewski, M. A., Wortsman, J., & Paus, R. (2008). Melatonin in the skin: Synthesis, metabolism and functions. Trends in Endocrinology and Metabolism, 19(1), 17–24.

    Article  PubMed  Google Scholar 

  • Tordjman, S., Anderson, G. M., Pichard, N., Charbuy, H., & Touitou, Y. (2005). Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biological Psychiatry, 57(2), 134–138.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Williams, P. G., Sears, L. L., & Allard, A. (2004). Sleep problems in children with autism. Journal of Sleep Research, 13, 265–268.

    Article  Google Scholar 

  • Wirojanan, J., Jacquemont, S., Diaz, R., Bacalman, S., Anders, T. F., Hagerman, R. J., et al. (2009). The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. Journal of Clinical Sleep Medicine, 5(2), 145–150.

    PubMed  Google Scholar 

Download references

Acknowledgments

Support provided by the National Alliance for Autism Research/Autism Speaks Foundation.

Author information

Authors and Affiliations

  1. Sleep Disorders Division, Department of Neurology, Vanderbilt University School of Medicine, Medical Center North, Room A-0118, 1161 21st Avenue South, Nashville, TN, 37232-2551, USA

    Roberta M. Leu, Liya Beyderman, Kyla Surdyka & Beth A. Malow

  2. Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA

    Lily Wang

  3. Vanderbilt Kennedy Center for Human Development, Vanderbilt University, Nashville, TN, USA

    Beth A. Malow

  4. Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, TN, USA

    Emmanuel J. Botzolakis

Authors
  1. Roberta M. Leu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liya Beyderman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emmanuel J. Botzolakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyla Surdyka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lily Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Beth A. Malow
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Beth A. Malow.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leu, R.M., Beyderman, L., Botzolakis, E.J. et al. Relation of Melatonin to Sleep Architecture in Children with Autism. J Autism Dev Disord 41, 427–433 (2011). https://doi.org/10.1007/s10803-010-1072-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-010-1072-1

Keywords

Search

Navigation