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Melatonin Use in Autism Spectrum Disorders

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Comprehensive Guide to Autism

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Abstract

Melatonin is a neurohormone secreted by the pineal gland. It is synthesized from the amino acid tryptophan and undergoes catabolism in the body. These children commonly have disturbances with their sleep, with the most common being insomnia. Melatonin has been used quite effectively in this subgroup of children; however, optimal dosing is still not clear.

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References

  • Andersen IM, Kaczmarska J, McGrew SG, et al. Melatonin for insomnia in children with autism spectrum disorders. J Child Neurol. 2008;23:482–5.

    Article  PubMed  Google Scholar 

  • Arendt J. Aaron Lerner, who discovered melatonin. J Pineal Res. 2007;43:106–7.

    Article  PubMed  Google Scholar 

  • Arendt J, Skene DJ. Melatonin as a chronobiotic. Sleep Med Rev. 2005;9:25–39.

    Article  PubMed  Google Scholar 

  • Attenburrow ME, Cowen PJ, Sharpley AL. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berl). 1996;126:179–81.

    Article  Google Scholar 

  • Birkeland AJ. Plasma melatonin levels and nocturnal transitions between sleep and wakefulness. Neuroendocrinology. 1982;34:126–31.

    Article  PubMed  Google Scholar 

  • Bourgeron T. The possible interplay of synaptic and clock genes in autism spectrum disorders. Cold Spring Harb Symp Quant Biol. 2007;72:645–54.

    Article  PubMed  Google Scholar 

  • Braam W, Didden R, Maas AP, Korzilius H, et al. Melatonin decreases daytime challenging behaviour in persons with intellectual disability and chronic insomnia. J Intellect Disabil Res. 2010;54:52–9.

    Article  PubMed  Google Scholar 

  • Carter M, Calcutt M, Malow B, et al. Quantitation of melatonin and n-acetylserotonin in human plasma by nanoflow LC-MS/MS and electrospray LC-MS/MS. J Mass Spectrom. 2012;47:277–85.

    Article  PubMed  Google Scholar 

  • Claustrat B, Brun J, Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev. 2005;9:11–24.

    Article  PubMed  Google Scholar 

  • Cotton S, Richdale A. Brief report: parental descriptions of sleep problems in children with autism, down syndrome, and prader-willi syndrome. Res Dev Disabil. 2006;27:151–61.

    Article  PubMed  Google Scholar 

  • Cricco M, Simonsick EM, Foley DJ. The impact of insomnia on cognitive functioning in older adults. J Am Geriatr Soc. 2001;49:1185–9.

    Article  PubMed  Google Scholar 

  • De Leersnyder H, De Blois MC, Claustrat B, et al. Inversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome. J Pediatr. 2001;139:111–6.

    Article  PubMed  Google Scholar 

  • Dijk DJ, von Schantz M. Timing and consolidation of human sleep, wakefulness, and performance by a symphony of oscillators. J Biol Rhythms. 2005;20:279–90.

    Article  PubMed  Google Scholar 

  • Doo S, Wing YK. Sleep problems of children with pervasive developmental disorders: correlation with parental stress. Dev Med Child Neurol. 2006;48:650–5.

    Article  PubMed  Google Scholar 

  • Dollins AB, Zhdanova IV, Wurtman RJ, et al. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci USA. 1994;91:1824–8.

    Article  PubMed  Google Scholar 

  • Doyen C, Mighiu D, Kaye K, et al. Melatonin in children with autistic spectrum disorders: recent and practical data. Eur Child Adolesc Psychiatry. 2011;20:231–9.

    Article  PubMed  Google Scholar 

  • Galli-Carminati G, Deriaz N, Bertschy G. Melatonin in treatment of chronic sleep disorders in adults with autism: a retrospective study. Swiss Med Wkly. 2009;139:293–6.

    PubMed  Google Scholar 

  • Garstang J, Wallis M. Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child Care Health Dev. 2006;32:585–9.

    Article  PubMed  Google Scholar 

  • Giannotti F, Cortesi F, Cerquiglini A, et al. An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism. J Autism Dev Disord. 2006;36:741–52.

    Article  PubMed  Google Scholar 

  • Giannotti F, Cortesi F, Cerquig, et al. An investigation of sleep characteristics, EEG abnormalities and epilepsy in developmentally regressed and non-regressed children with autism. J Autism Dev Disord. 2008;38:1888–97.

    Article  PubMed  Google Scholar 

  • Glickman G. Circadian rhythms and sleep in children with autism. Neurosci Biobehav Rev. 2010;34:755–68.

    Article  PubMed  Google Scholar 

  • Gupta R, Hutchins J. Melatonin: a panacea for desperate parents? (Hype or truth). Arch Dis Child. 2005;90:986–7.

    Article  PubMed  Google Scholar 

  • Hayashi E. Effect of melatonin on sleep-wake rhythm: the sleep diary of an autistic male. Psychiatry Clin Neurosci. 2000;54:383–4.

    Article  PubMed  Google Scholar 

  • Hirata F, Hayaishi O, Tokuyama T, et al. In vitro and in vivo formation of two new metabolites of melatonin. J Biol Chem. 1974;249:1311–3.

    PubMed  Google Scholar 

  • Horrigan JP, Barnhill LJ. More on melatonin. J Am Acad Child Adolesc Psychiatry. 1997;36:1014.

    Article  PubMed  Google Scholar 

  • Jan JE, Espezel H, Appleton RE. The treatment of sleep disorders with melatonin. Dev Med Child Neurol. 1994;36:97–107.

    Article  PubMed  Google Scholar 

  • Jan JE, Freeman RD, Wasdell MB, et al. A child with severe night terrors and sleep-walking responds to melatonin therapy. Dev Med Child Neurol. 2004;46:789.

    Article  PubMed  Google Scholar 

  • Jang SW, Liu X, Pradoldej S, et al. N-acetylserotonin activates TrkB receptor in a circadian rhythm. Proc Natl Acad Sci USA. 2010;107:3876–81.

    Article  PubMed  Google Scholar 

  • Jin X, von Gall C, Pieschl RL, et al. Targeted disruption of the mouse mel (1b) melatonin receptor. Mol Cell Biol. 2003;23:1054–60.

    Article  PubMed  Google Scholar 

  • Kato K, Hirai K, Nishiyama K, et al. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology. 2005;48:301–10.

    Article  PubMed  Google Scholar 

  • Klein DC, Weller JL, Moore RY. Melatonin metabolism: neural regulation of pineal serotonin: acetyl coenzyme A N-acetyltransferase activity. Proc Natl Acad Sci USA. 1971;68:3107–10.

    Article  PubMed  Google Scholar 

  • Klein DC, Schaad NL, Namboordiri MA, et al. Regulation of pineal serotonin N-acetyltransferase activity. Biochem Soc Trans. 1992;20:299–304.

    PubMed  Google Scholar 

  • Konturek PC, Brzozowski T, Konturek SJ. Gut clock: implication of circadian rhythms in the gastrointestinal tract. J Physiol Pharmacol. 2011;62:139–50.

    PubMed  Google Scholar 

  • Konstantareas MM, Homatidis S. Assessing child symptom severity and stress in parents of autistic children. J Child Psychol Psychiatry. 1989:30;459–70.

    Article  PubMed  Google Scholar 

  • Krakowiak P, Goodlin-Jones B, Hertz-Picciotto I, et al. Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study. J Sleep Res. 2008;17;197–206.

    Article  PubMed  Google Scholar 

  • Kripke DF, Nievergelt CM, Tranah GJ, et al. Polymorphisms in melatonin synthesis pathways: possible influences on depression. J Circadian Rhythms. 2011;9:8.

    Article  PubMed  Google Scholar 

  • Kulman G, Lissoni P, Rovelli F, et al. Evidence of pineal endocrine hypofunction in autistic children. Neuro Endocrinol Lett. 2000;21:31–4.

    PubMed  Google Scholar 

  • Leu RM, Beyderman L, Botzolakis EJ, et al. Relation of melatonin to sleep architecture in children with autism. J Autism Dev Disord. 2011;41:427–33.

    Article  PubMed  Google Scholar 

  • Leyfer OT, Folstein SE, Bacalman S, et al. Comorbid psychiatric disorders in children with autism: interview development and rates of disorders. J Autism Dev Disord. 2006;36:849–61.

    Article  PubMed  Google Scholar 

  • Liu X, Hubbard JA, Fabes RA, et al. Sleep disturbances and correlates of children with autism spectrum disorders. Child Psychiatry Hum Dev. 2006;37:179–91.

    Article  PubMed  Google Scholar 

  • Ma X, Idle JR, Krausz KW, et al. Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos. 2005;33:489–94.

    Article  PubMed  Google Scholar 

  • Malow BA, McGrew SG, Harvey M, et al. Impact of treating sleep apnea in a child with autism spectrum disorder. Pediatr Neurol. 2006a;34:325–8.

    Article  PubMed  Google Scholar 

  • Malow BA, Marzec ML, McGrew SG, et al. Characterizing sleep in children with autism spectrum disorders: a multidimensional approach. Sleep. 2006b;29:1563–71.

    PubMed  Google Scholar 

  • Malow B, Adkins KW, McGrew SG, et al. Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. J Autism Dev Disord. 2012;42:1729–37.

    Google Scholar 

  • Meltzer LJ. Brief report: sleep in parents of children with autism spectrum disorders. J Pediatr Psychol. 2008;33:380–6.

    Article  PubMed  Google Scholar 

  • Melke J, Goubran Botros H, Chaste P, et al. Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry. 2008;13:90–8.

    Article  PubMed  Google Scholar 

  • Morin LP, Allen CN. The circadian visual system, 2005. Brain Res Rev. 2006;51:1–60.

    Article  PubMed  Google Scholar 

  • Nir I, Meir D, Zilber N, et al. Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism. J Autism Dev Disord. 1995;25:641–54.

    Article  PubMed  Google Scholar 

  • Owens JA. The ADHD and sleep conundrum: a review. J Dev Behav Pediatr. 2005;26:312–22.

    Article  PubMed  Google Scholar 

  • Paavonen EJ, Nieminen-von Wendt T, Vanhala R, et al. Effectiveness of melatonin in the treatment of sleep disturbances in children with asperger disorder. J Child Adolesc Psychopharmacol. 2003;13:83–95.

    Article  PubMed  Google Scholar 

  • Pandi-Perumal SR, Srinivasan V, Maestroni GJ, et al. Melatonin: nature’s most versatile biological signal? FEBS J. 2006;273:2813–38.

    Article  PubMed  Google Scholar 

  • Patzold LM, Richdale AL, Tonge BJ. An investigation into sleep characteristics of children with autism and Asperger's Disorder. J Paediatr Child Health. 1998;34:528–33.

    Article  PubMed  Google Scholar 

  • Phillips L, Appleton RE. Systematic review of melatonin treatment in children with neurodevelopmental disabilities and sleep impairment. Dev Med Child Neurol. 2004;46:771–5.

    Article  PubMed  Google Scholar 

  • Reiter RJ. Melatonin: clinical relevance. Best Pract Res Clin Endocrinol Metab. 2003;17:273–85.

    Article  PubMed  Google Scholar 

  • Reppert SM, Godson C, Mahle CD, et al. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci USA. 1995;92:8734–8.

    Article  PubMed  Google Scholar 

  • Richdale AL. Sleep problems in autism: prevalence, cause, and intervention. Dev Med Child Neurol. 1999;41:60–6.

    Article  PubMed  Google Scholar 

  • Richdale AL, Schreck KA. Sleep problems in autism spectrum disorders: prevalence, nature, & possible biopsychosocial aetiologies. Sleep Med Rev. 2009;13:403–11.

    Article  PubMed  Google Scholar 

  • Richdale AL, Prior MR. The sleep/wake rhythm in children with autism. Eur Child Adolesc Psychiatry. 1995;4:175–86.

    Article  PubMed  Google Scholar 

  • Robinson AM, Richdale AL. Sleep problems in children with an intellectual disability: parental perceptions of sleep problems, and views of treatment effectiveness. Child Care Health Dev. 2004;30:139–50.

    Article  PubMed  Google Scholar 

  • Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol. 2011;53:783–92.

    Article  PubMed  Google Scholar 

  • Sack RL, Hughes RJ, Edgar DM, et al. Sleep-promoting effects of melatonin: at what dose, in whom, under what conditions, and by what mechanisms? Sleep. 1997;20:908–15.

    PubMed  Google Scholar 

  • Schreck KA, Mulick JA, Smith AF. Sleep problems as possible predictors of intensified symptoms of autism. Res Dev Disabil. 2004;25:57–66.

    Article  PubMed  Google Scholar 

  • Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet. 1998;351:1254.

    Article  PubMed  Google Scholar 

  • Smith AC, Dykens E, Greenberg F. Behavioral phenotype of smith-magenis syndrome (del 17p11.2). Am J Med Genet. 1998;81:179–85.

    Article  PubMed  Google Scholar 

  • Souders MC, Mason TB, Valladares O, et al. Sleep behaviors and sleep quality in children with autism spectrum disorders. Sleep. 2009;32:1566–78.

    PubMed  Google Scholar 

  • Tordjman S, Anderson GM, Pichard N, et al. Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biol Psychiatry. 2005;57:134–8.

    Article  PubMed  Google Scholar 

  • Tricoire H, Moller M, Chemineau P, et al. Origin of cerebrospinal fluid melatonin and possible function in the integration of photoperiod. Reprod Suppl. 2003;61:311–21.

    PubMed  Google Scholar 

  • Waldhauser F, Steger H. Changes in melatonin secretion with age and pubescence. J Neural Transm Suppl. 1986;21:183–97.

    PubMed  Google Scholar 

  • Weaver DR. Reproductive safety of melatonin: a “wonder drug” to wonder about. J Biol Rhythms. 1997;12:682–9.

    Article  PubMed  Google Scholar 

  • Wiggs L, Stores G. Sleep patterns and sleep disorders in children with autistic spectrum disorders: insights using parent report and actigraphy. Dev Med Child Neurol. 2004;46:372–80.

    Article  PubMed  Google Scholar 

  • Wirojanan J, Jacquemont S, Diaz R, et al. The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. J Clin Sleep Med. 2009;5:145–50.

    PubMed  Google Scholar 

  • Wright B, Sims D, Smart S, et al. Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial. J Autism Dev Disord. 2011;41:175–84.

    Article  PubMed  Google Scholar 

  • Zhdanova IV. Melatonin as a hypnotic: pro. Sleep Med Rev. 2005;9:51–65.

    Article  PubMed  Google Scholar 

  • Zhdanova IV, Wurtman RJ, Lynch HJ, et al. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther. 1995;57:552–8.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, 4301 W Markham St # 531, 72205, Little Rock, AR, USA

    Sheila J. Asghar

  2. Vanderbilt Kennedy Center, Vanderbilt University, PMB 40, 230 Appleton Place, 37203-5721, Nashville, TN, USA

    Beth A. Malow

Authors
  1. Sheila J. Asghar
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  2. Beth A. Malow
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Correspondence to Beth A. Malow .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, Faculty of Science & Technology, London, United Kingdom

    Vinood B. Patel

  2. Nutritional Sciences Division and Genomics Centre, King's College London, London, United Kingdom

    Victor R. Preedy

  3. Faculty of Society and Health, Buckinghamshire New University, Middlesex, United Kingdom

    Colin R. Martin

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Asghar, S.J., Malow, B.A. (2014). Melatonin Use in Autism Spectrum Disorders. In: Patel, V., Preedy, V., Martin, C. (eds) Comprehensive Guide to Autism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4788-7_146

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  • DOI: https://doi.org/10.1007/978-1-4614-4788-7_146

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  • Print ISBN: 978-1-4614-4787-0

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