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Open Access 01-12-2022 | Autism Spectrum Disorder | Review

Biological correlates of altered circadian rhythms, autonomic functions and sleep problems in autism spectrum disorder

Authors: Liliana Dell’Osso, Leonardo Massoni, Simone Battaglini, Ivan Mirko Cremone, Claudia Carmassi, Barbara Carpita

Published in: Annals of General Psychiatry | Issue 1/2022

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by a complex and multifaceted neurobehavioral syndrome. In the last decades, several studies highlighted an increased prevalence of sleep problems in ASD, which would be associated with autonomic system and circadian rhythm disruption. The present review aimed to summarize the available literature about sleep problems in ASD subjects and about the possible biological factors implicated in circadian rhythm and autonomic system deregulation in this population, as well as possible therapeutic approaches. Shared biological underpinnings between ASD symptoms and altered circadian rhythms/autonomic functions are also discussed. Studies on sleep showed how ASD subjects typically report more problems regarding insufficient sleep time, bedtime resistance and reduced sleep pressure. A link between sleep difficulties and irritability, deficits in social skills and behavioral problems was also highlighted. Among the mechanisms implicated, alteration in genes related to circadian rhythms, such as CLOCK genes, and in melatonin levels were reported. ASD subjects also showed altered hypothalamic pituitary adrenal (HPA) axis and autonomic functions, generally with a tendency towards hyperarousal and hyper sympathetic state. Intriguingly, some of these biological alterations in ASD individuals were not associated only with sleep problems but also with more autism-specific clusters of symptoms, such as communication impairment or repetitive behaviors Although among the available treatments melatonin showed promising results, pharmacological studies for sleep problems in ASD need to follow more standardized protocols to reach more repeatable and reliable results. Further research should investigate the issue of sleep problems in ASD in a broader perspective, taking into account shared pathophysiological mechanisms for core and associated symptoms of ASD.

Biran J, Tahor M, Wircer E, Levkowitz G. Role of developmental factors in hypothalamic function. Front Neuroanat. 2015;9:47. https://doi.org/10.3389/fnana.2015.00047.CrossRefPubMedPubMedCentral

Caria A, Ciringione L, Falco S. Morphofunctional alterations of the hypothalamus and social behavior in autism spectrum disorders. Brain Sci. 2020;10(7):435. https://doi.org/10.3390/brainsci10070435.CrossRefPubMedCentral

Lorsung E, Karthikeyan R, Cao R. Biological timing and neurodevelopmental disorders: a role for circadian dysfunction in autism spectrum disorders. Front Neurosci. 2021;15: 642745. https://doi.org/10.3389/fnins.2021.642745.CrossRefPubMedPubMedCentral

Malow BA, Marzec ML, McGrew SG, Wang L, Henderson LM, Stone WL. Characterizing sleep in children with autism spectrum disorders: a multidimensional approach. Sleep. 2006;29(12):1563–71. https://doi.org/10.1093/sleep/29.12.1563.CrossRefPubMed

Hu VW, Sarachana T, Kim KS, Nguyen A, Kulkarni S, Steinberg ME, Luu T, Lai Y, Lee NH. Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism. Autism Res. 2009;2(2):78–97. https://doi.org/10.1002/aur.73.CrossRefPubMedPubMedCentral

Wu ZY, Huang SD, Zou JJ, Wang QX, Naveed M, Bao HN, Wang W, Fukunaga K, Han F. Autism spectrum disorder (ASD): disturbance of the melatonin system and its implications. Biomed Pharmacother. 2020;130: 110496. https://doi.org/10.1016/j.biopha.2020.110496.CrossRefPubMed

Baker EK, Richdale AL, Hazi A, Prendergast LA. Assessing a hyperarousal hypothesis of insomnia in adults with autism spectrum disorder. Autism Res. 2019;12(6):897–910. https://doi.org/10.1002/aur.2094.CrossRefPubMed

Bharath R, Moodithaya SS, Bhat SU, Mirajkar AM, Shetty SB. Comparison of physiological and biochemical autonomic indices in children with and without autism spectrum disorders. Medicina. 2019;55(7):346. https://doi.org/10.3390/medicina55070346.CrossRefPubMedCentral

Condy EE, Scarpa A, Friedman BH. Respiratory sinus arrhythmia predicts restricted repetitive behavior severity. J Autism Dev Disord. 2017;47(9):2795–804. https://doi.org/10.1007/s10803-017-3193-2.CrossRefPubMed

10.

Wright B, Sims D, Smart S, Alwazeer A, Alderson-Day B, Allgar V, Whitton C, Tomlinson H, Bennett S, Jardine J, McCaffrey N, Leyland C, Jakeman C, Miles J. Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behavior management strategies: a randomised controlled crossover trial. J Autism Dev Disord. 2011;41(2):175–84. https://doi.org/10.1007/s10803-010-1036-5.CrossRefPubMed

11.

Rana M, Kothare S, DeBassio W. The assessment and treatment of sleep abnormalities in children and adolescents with autism spectrum disorder: a review. J Can Acad Child Adolesc Psychiatry. 2021;30(1):25–35.PubMedPubMedCentral

12.

Kotagal S, Broomall E. Sleep in children with autism spectrum disorder. Pediatr Neurol. 2012;47(4):242–51. https://doi.org/10.1016/j.pediatrneurol.2012.05.007.CrossRefPubMed

13.

Schreck KA, Mulick JA, Smith AF. Sleep problems as possible predictors of intensified symptoms of autism. Res Dev Disabil. 2004;25(1):57–66. https://doi.org/10.1016/j.ridd.2003.04.007.CrossRefPubMed

14.

Sikora DM, Johnson K, Clemons T, Katz T. The relationship between sleep problems and daytime behavior in children of different ages with autism spectrum disorders. Pediatrics. 2012;130(Suppl 2):S83-90. https://doi.org/10.1542/peds.2012-0900F.CrossRefPubMed

15.

Goldman SE, Richdale AL, Clemons T, Malow BA. Parental sleep concerns in autism spectrum disorders: variations from childhood to adolescence. J Autism Dev Disord. 2012;42(4):531–8. https://doi.org/10.1007/s10803-011-1270-5.CrossRefPubMed

16.

Horiuchi F, Kawabe K, Oka Y, Nakachi K, Hosokawa R, Ueno SI. The association between autistic traits and sleep habits/problems in toddlers. Dev Neuropsychol. 2020;45(7–8):485–95. https://doi.org/10.1080/87565641.2020.1865357.CrossRefPubMed

17.

Türkoğlu S, Uçar HN, Çetin FH, Güler HA, Tezcan ME. The relationship between chronotype, sleep, and autism symptom severity in children with ASD in COVID-19 home confinement period. Chronobiol Int. 2020;37(8):1207–13. https://doi.org/10.1080/07420528.2020.1792485.CrossRefPubMed

18.

Miike T, Toyoura M, Tonooka S, Konishi Y, Oniki K, Saruwatari J, Tajima S, Kinoshita J, Nakai A, Kikuchi K. Neonatal irritable sleep-wake rhythm as a predictor of autism spectrum disorders. Neurobiol Sleep Circadian Rhythm. 2020;9: 100053. https://doi.org/10.1016/j.nbscr.2020.100053.CrossRef

19.

Yavuz-Kodat E, Reynaud E, Geoffray MM, Limousin N, Franco P, Bonnet-Brilhault F, Bourgin P, Schroder CM. Disturbances of continuous sleep and circadian rhythms account for behavioral difficulties in children with autism spectrum disorder. J Clin Med. 2020;9(6):1978. https://doi.org/10.3390/jcm9061978.CrossRefPubMedCentral

20.

Ballester P, Martínez MJ, Javaloyes A, Inda MD, Fernández N, Gázquez P, Aguilar V, Pérez A, Hernández L, Richdale AL, Peiró AM. Sleep problems in adults with autism spectrum disorder and intellectual disability. Autism Res. 2019;12(1):66–79. https://doi.org/10.1002/aur.2000.CrossRefPubMed

21.

Jovevska S, Richdale AL, Lawson LP, Uljarević M, Arnold SRC, Trollor JN. Sleep quality in autism from adolescence to old age. Autism Adulthood. 2020;2(2):152–62. https://doi.org/10.1089/aut.2019.0034.CrossRef

22.

Baker EK, Richdale AL, Hazi A. Employment status is related to sleep problems in adults with autism spectrum disorder and no comorbid intellectual impairment. Autism. 2019;23(2):531–6. https://doi.org/10.1177/1362361317745857.CrossRefPubMed

23.

Deserno MK, Borsboom D, Begeer S, van RentergemAgelink JA, Mataw K, Geurts HM. Sleep determines quality of life in autistic adults: a longitudinal study. Autism Res. 2019;12(5):794–801. https://doi.org/10.1002/aur.2103.CrossRefPubMedPubMedCentral

24.

Charrier A, Olliac B, Roubertoux P, Tordjman S. Clock genes and altered sleep-wake rhythms: their role in the development of psychiatric disorders. Int J Mol Sci. 2017;18(5):938. https://doi.org/10.3390/ijms18050938.CrossRefPubMedCentral

25.

Bhatti P, Zhang Y, Song X, Makar KW, Sather CL, Kelsey KT, Houseman EA, Wang P. Nightshift work and genome-wide DNA methylation. Chronobiol Int. 2015;32(1):103–12. https://doi.org/10.3109/07420528.2014.956362.CrossRefPubMed

26.

Schuch JB, Genro JP, Bastos CR, Ghisleni G, Tovo-Rodrigues L. The role of CLOCK gene in psychiatric disorders: evidence from human and animal research. Am J Med Genet B Neuropsychiatr Genet. 2018;177(2):181–98. https://doi.org/10.1002/ajmg.b.32599.CrossRefPubMed

27.

Nicholas B, Rudrasingham V, Nash S, Kirov G, Owen MJ, Wimpory DC. Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis. Mol Psychiatry. 2007;12(6):581–92. https://doi.org/10.1038/sj.mp.4001953.CrossRefPubMed

28.

Nikkie Olde Loohuis FM, Martens GJM, van Bokhoven H, Kaplan BB, Homberg JR, Aschrafi A. Altered expression of circadian rhythm and extracellular matrix genes in the medial prefrontal cortex of a valproic acid rat model of autism. Prog Neuropsychopharmacol Biol Psychiatry. 2017;77:128–32. https://doi.org/10.1016/j.pnpbp.2017.04.009.CrossRefPubMed

29.

Yang Z, Matsumoto A, Nakayama K, Jimbo EF, Kojima K, Nagata K, Iwamoto S, Yamagata T. Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients. Brain Dev. 2016;38(1):91–9. https://doi.org/10.1016/j.braindev.2015.04.006.CrossRefPubMed

30.

Abel EA, Schwichtenberg AJ, Mannin OR, Marceau K. Brief report: a gene enrichment approach applied to sleep and autism. J Autism Dev Disord. 2020;50(5):1834–40. https://doi.org/10.1007/s10803-019-03921-5.CrossRefPubMedPubMedCentral

31.

Baker EK, Richdale AL, Hazi A, Prendergast LA. Assessing the dim light melatonin onset in adults with autism spectrum disorder and no comorbid intellectual disability. J Autism Dev Disord. 2017;47(7):2120–37. https://doi.org/10.1007/s10803-017-3122-4.CrossRefPubMed

32.

Pagan C, Delorme R, Callebert J, Goubran-Botros H, Amsellem F, Drouot X, Boudebesse C, Le Dudal K, Ngo-Nguyen N, Laouamri H, Gillberg C, Leboyer M, Bourgeron T, Launay JM. The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders. Transl Psychiatry. 2014;4(11): e479. https://doi.org/10.1038/tp.2014.120.CrossRefPubMedPubMedCentral

33.

Braam W, Ehrhart F, Maas APHM, Smits MG, Curfs L. Low maternal melatonin level increases autism spectrum disorder risk in children. Res Dev Disabil. 2018;82:79–89. https://doi.org/10.1016/j.ridd.2018.02.017.CrossRefPubMed

34.

Jin Y, Choi J, Won J, Hong Y. The relationship between autism spectrum disorder and melatonin during fetal development. Molecules. 2018;23(1):198. https://doi.org/10.3390/molecules23010198.CrossRefPubMedCentral

35.

Lalanne S, Fougerou-Leurent C, Anderson GM, Schroder CM, Nir T, Chokron S, Delorme R, Claustrat B, Bellissant E, Kermarrec S, Franco P, Denis L, Tordjman S. Melatonin: from pharmacokinetics to clinical use in autism spectrum disorder. Int J Mol Sci. 2021;22(3):1490. https://doi.org/10.3390/ijms22031490.CrossRefPubMedPubMedCentral

36.

Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol. 2011;53(9):783–92. https://doi.org/10.1111/j.1469-8749.2011.03980.x.CrossRefPubMed

37.

Jonsson L, Ljunggren E, Bremer A, Pedersen C, Landén M, Thuresson K, Giacobini M, Melke J. Mutation screening of melatonin-related genes in patients with autism spectrum disorders. BMC Med Genom. 2010;3:10. https://doi.org/10.1186/1755-8794-3-10.CrossRef

38.

Hansen RL, Ozonoff S, Krakowiak P, Angkustsiri K, Jones C, Deprey LJ, Le DN, Croen LA, Hertz-Picciotto I. Regression in autism: prevalence and associated factors in the CHARGE study. Ambul Pediatr. 2008;8(1):25–31. https://doi.org/10.1016/j.ambp.2007.08.006.CrossRefPubMed

39.

Melke J, Goubran Botros H, Chaste P, Betancur C, Nygren G, Anckarsäter H, Rastam M, Ståhlberg O, Gillberg IC, Delorme R, Chabane N, Mouren-Simeoni MC, Fauchereau F, Durand CM, Chevalier F, Drouot X, Collet C, Launay JM, Leboyer M, Gillberg C, Bourgeron T. Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry. 2008;13(1):90–8. https://doi.org/10.1038/sj.mp.4002016.CrossRefPubMed

40.

Wang L, Li J, Ruan Y, Lu T, Liu C, Jia M, Yue W, Liu J, Bourgeron T, Zhang D. Sequencing ASMT identifies rare mutations in Chinese Han patients with autism. PLoS ONE. 2013;8(1): e53727. https://doi.org/10.1371/journal.pone.0053727.CrossRefPubMedPubMedCentral

41.

Veatch OJ, Pendergast JS, Allen MJ, Leu RM, Johnson CH, Elsea SH, Malow BA. Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay. J Autism Dev Disord. 2015;45(1):100–10. https://doi.org/10.1007/s10803-014-2197-4.CrossRefPubMedPubMedCentral

42.

Chaste P, Clement N, Mercati O, Guillaume JL, Delorme R, Botros HG, Pagan C, Périvier S, Scheid I, Nygren G, Anckarsäter H, Rastam M, Ståhlberg O, Gillberg C, Serrano E, Lemière N, Launay JM, Mouren-Simeoni MC, Leboyer M, Gillberg C, Jockers R, Bourgeron T. Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population. PLoS ONE. 2010;5(7): e11495. https://doi.org/10.1371/journal.pone.0011495.CrossRefPubMedPubMedCentral

43.

Carmassi C, Palagini L, Caruso D, Masci I, Nobili L, Vita A, Dell’Osso L. Systematic review of sleep disturbances and circadian sleep desynchronization in autism spectrum disorder: toward an integrative model of a self-reinforcing loop. Front Psychiatry. 2019;10:366. https://doi.org/10.3389/fpsyt.2019.00366.CrossRefPubMedPubMedCentral

44.

Pagan C, Goubran-Botros H, Delorme R, Benabou M, Lemière N, Murray K, Amsellem F, Callebert J, Chaste P, Jamain S, Fauchereau F, Huguet G, Maronde E, Leboyer M, Launay JM, Bourgeron T. Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders. Sci Rep. 2017;7(1):2096. https://doi.org/10.1038/s41598-017-02152-x.CrossRefPubMedPubMedCentral

45.

Maruani A, Dumas G, Beggiato A, Traut N, Peyre H, Cohen-Freoua A, Amsellem F, Elmaleh M, Germanaud D, Launay JM, Bourgeron T, Toro R, Delorme R. morning plasma melatonin differences in autism: beyond the impact of pineal gland volume. Front Psychiatry. 2019;10:11. https://doi.org/10.3389/fpsyt.2019.00011.CrossRefPubMedPubMedCentral

46.

Tordjman S, Anderson GM, Pichard N, Charbuy H, Touitou Y. Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biol Psychiatry. 2005;57(2):134–8. https://doi.org/10.1016/j.biopsych.2004.11.003.CrossRefPubMed

47.

Nir I, Meir D, Zilber N, Knobler H, Hadjez J, Lerner Y. Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism. J Autism Dev Disord. 1995;25(6):641–54. https://doi.org/10.1007/BF02178193.CrossRefPubMed

48.

Muscatello RA, Corbett BA. Comparing the effects of age, pubertal development, and symptom profile on cortisol rhythm in children and adolescents with autism spectrum disorder. Autism Res. 2018;11(1):110–20. https://doi.org/10.1002/aur.1879.CrossRefPubMed

49.

Priya Lakshmi MD, Geetha A, Suganya V, Sujatha S. Abnormal circadian rhythm and cortisol excretion in autistic children: a clinical study. Croat Med J. 2013;54(1):33–41. https://doi.org/10.3325/cmj.2013.54.33.CrossRef

50.

Tomarken AJ, Han GT, Corbett BA. Temporal patterns, heterogeneity, and stability of diurnal cortisol rhythms in children with autism spectrum disorder. Psychoneuroendocrinology. 2015;62:217–26. https://doi.org/10.1016/j.psyneuen.2015.08.016.CrossRefPubMedPubMedCentral

51.

Gabriels RL, Agnew JA, Pan Z, Holt KD, Reynolds A, Laudenslager ML. Elevated repetitive behaviors are associated with lower diurnal salivary cortisol levels in autism spectrum disorder. Biol Psychol. 2013;93(2):262–8. https://doi.org/10.1016/j.biopsycho.2013.02.017.CrossRefPubMed

52.

Corbett BA, Schupp CW. The cortisol awakening response (CAR) in male children with autism spectrum disorder. Horm Behav. 2014;65(4):345–50. https://doi.org/10.1016/j.yhbeh.2014.01.012.CrossRefPubMedPubMedCentral

53.

Sharpley CF, Bitsika V, Andronicos NM, Agnew LL. Further evidence of HPA-axis dysregulation and its correlation with depression in autism spectrum disorders: data from girls. Physiol Behav. 2016;167:110–7. https://doi.org/10.1016/j.physbeh.2016.09.003.CrossRefPubMed

54.

Anesiadou S, Makris G, Michou M, Bali P, Papassotiriou I, Apostolakou F, Korkoliakou P, Papageorgiou C, Chrousos G, Pervanidou P. Salivary cortisol and alpha-amylase daily profiles and stress responses to an academic performance test and a moral cognition task in children with neurodevelopmental disorders. Stress Health. 2021;37(1):45–59. https://doi.org/10.1002/smi.2971.CrossRefPubMed

55.

Pruessner JC, Wolf OT, Hellhammer DH, Buske-Kirschbaum A, von Auer K, Jobst S, Kaspers F, Kirschbaum C. Free cortisol levels after awakening: a reliable biological marker for the assessment of adrenocortical activity. Life Sci. 1997;61(26):2539–49. https://doi.org/10.1016/s0024-3205(97)01008-4.CrossRefPubMed

56.

Kidd SA, Corbett BA, Granger DA, Boyce WT, Anders TF, Tager IB. Daytime secretion of salivary cortisol and alpha-amylase in preschool-aged children with autism and typically developed children. J Autism Dev Disord. 2012;42(12):2648–58. https://doi.org/10.1007/s10803-012-1522-z.CrossRefPubMedPubMedCentral

57.

Muskens JB, Velders FP, Staal WG. Medical comorbidities in children and adolescents with autism spectrum disorders and attention deficit hyperactivity disorders: a systematic review. Eur Child Adolesc Psychiatry. 2017;26(9):1093–103. https://doi.org/10.1007/s00787-017-1020-0.CrossRefPubMedPubMedCentral

58.

Bauman ML. Medical comorbidities in autism: challenges to diagnosis and treatment. Neurotherapeutics. 2010;7(3):320–7. https://doi.org/10.1016/j.nurt.2010.06.001.CrossRefPubMedPubMedCentral

59.

Sheinkopf SJ, Levine TP, McCormick CEB, Puggioni G, Conradt E, Lagasse LL, Lester BM. Developmental trajectories of autonomic functioning in autism from birth to early childhood. Biol Psychol. 2019;142:13–8. https://doi.org/10.1016/j.biopsycho.2019.01.003.CrossRefPubMedPubMedCentral

60.

Mohd MS, Aimie-Salleh N, Wahab AHA, Sahalan M, Ashari UMM. Heart rate variability response on autism spectrum disorder and typical development children. In: 2020 4th international symposium on multidisciplinary studies and innovative technologies (ISMSIT). 2020. p. 1–3. https://doi.org/10.1109/ISMSIT50672.2020.9255015.

61.

Thapa R, Alvares GA, Zaidi TA, Thomas EE, Hickie IB, Park SH, Guastella AJ. Reduced heart rate variability in adults with autism spectrum disorder. Autism Res. 2019;12(6):922–30. https://doi.org/10.1002/aur.2104.CrossRefPubMed

62.

Anderson CJ, Colombo J, Unruh KE. Pupil and salivary indicators of autonomic dysfunction in autism spectrum disorder. Dev Psychobiol. 2013;55(5):465–82. https://doi.org/10.1002/dev.21051.CrossRefPubMed

63.

Arora I, Bellato A, Ropar D, Hollis C, Groom MJ. Is autonomic function during resting-state atypical in autism: a systematic review of evidence. Neurosci Biobehav Rev. 2021;125:417–41. https://doi.org/10.1016/j.neubiorev.2021.02.041.CrossRefPubMed

64.

Pace M, Dumortier L, Favre-Juvin A, Guinot M, Bricout VA. Heart rate variability during sleep in children with autism spectrum disorders. Physiol Behav. 2016;167:309–12. https://doi.org/10.1016/j.physbeh.2016.09.027.CrossRefPubMed

65.

Harder R, Malow BA, Goodpaster RL, Iqbal F, Halbower A, Goldman SE, Fawkes DB, Wang L, Shi Y, Baudenbacher F, Diedrich A. Heart rate variability during sleep in children with autism spectrum disorder. Clin Auton Res. 2016;26(6):423–32. https://doi.org/10.1007/s10286-016-0375-5.CrossRefPubMedPubMedCentral

66.

Tessier MP, Pennestri MH, Godbout R. Heart rate variability of typically developed and autistic children and adults before, during and after sleep. Int J Psychophysiol. 2018;134:15–21. https://doi.org/10.1016/j.ijpsycho.2018.10.004.CrossRefPubMed

67.

Chong PLH, Abel E, Pao R, McCormick CEB, Schwichtenberg AJ. Sleep dysregulation and daytime electrodermal patterns in children with autism: a descriptive study. J Genet Psychol. 2021;182(5):335–47. https://doi.org/10.1080/00221325.2021.1911919.CrossRefPubMed

68.

Sagar-Ouriaghli I, Lievesley K, Santosh PJ. Propranolol for treating emotional, behavioral, autonomic dysregulation in children and adolescents with autism spectrum disorders. J Psychopharmacol. 2018;32(6):641–53. https://doi.org/10.1177/0269881118756245.CrossRefPubMed

69.

Brown GM, Karthikeyan R, Pandi-Perumal SR, Cardinali DP. Autism spectrum disorder patients may be susceptible to covid-19 disease due to deficiency in melatonin. Med Hypotheses. 2021;149: 110544.CrossRef

70.

Vriend JL, Corkum PV, Moon EC, Smith IM. Behavioral interventions for sleep problems in children with autism spectrum disorders: current findings and future directions. J Pediatr Psychol. 2011;36(9):1017–29. https://doi.org/10.1093/jpepsy/jsr044.CrossRefPubMed

71.

Doyle CA, McDougle CJ. Pharmacotherapy to control behavioral symptoms in children with autism. Expert Opin Pharmacother. 2012;13(11):1615–29. https://doi.org/10.1517/14656566.2012.674110.CrossRefPubMed

72.

Wasdell MB, Jan JE, Bomben MM, Freeman RD, Rietveld WJ, Tai J, Hamilton D, Weiss MD. A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities. J Pineal Res. 2008;44(1):57–64. https://doi.org/10.1111/j.1600-079X.2007.00528.x.CrossRefPubMed

73.

Malow B, Adkins KW, McGrew SG, Wang L, Goldman SE, Fawkes D, Burnette C. Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. J Autism Dev Disord. 2012;42(8):1729–37. https://doi.org/10.1007/s10803-011-1418-3.CrossRefPubMedPubMedCentral

74.

Maras A, Schroder CM, Malow BA, Findling RL, Breddy J, Nir T, Shahmoon S, Zisapel N, Gringras P. Long-term efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder. J Child Adolesc Psychopharmacol. 2018;28(10):699–710. https://doi.org/10.1089/cap.2018.0020.CrossRefPubMedPubMedCentral

75.

Cuomo BM, Vaz S, Lee EAL, Thompson C, Rogerson JM, Falkmer T. Effectiveness of sleep-based interventions for children with autism spectrum disorder: a meta-synthesis. Pharmacotherapy. 2017;37(5):555–78. https://doi.org/10.1002/phar.1920.CrossRefPubMed

76.

Schroder CM, Malow BA, Maras A, Melmed RD, Findling RL, Breddy J, Nir T, Shahmoon S, Zisapel N, Gringras P. Pediatric prolonged-release melatonin for sleep in children with autism spectrum disorder: impact on child behavior and caregiver’s quality of life. J Autism Dev Disord. 2019;49(8):3218–30. https://doi.org/10.1007/s10803-019-04046-5.CrossRefPubMedPubMedCentral

77.

Ayuse T, Ozaki-Honda Y, Kurata S, Mishima G, Kiriishi K, Magata N, Kawasaki H, Yamaguchi-Komeyama K, Tanoue N, Ayuse T. Study on the preventive effect of ramelteon on the onset of sleep disorder after general anesthesia in patients with autism spectrum disorder: a study protocol. Medicine. 2020;99(43): e22826. https://doi.org/10.1097/MD.0000000000022826.CrossRefPubMedPubMedCentral

78.

Kawabe K, Horiuchi F, Oka Y, Ueno S. The melatonin receptor agonist ramelteon effectively treats insomnia and behavioral symptoms in autistic disorder. Case Rep Psychiatry. 2014;2014: 561071. https://doi.org/10.1155/2014/561071.CrossRefPubMedPubMedCentral

79.

Karthikeyan R, Cardinali DP, Shakunthala V, Spence DW, Brown GM, Pandi-Perumal SR. Understanding the role of sleep and its disturbances in autism spectrum disorder. Int J Neurosci. 2020;130(10):1033–46. https://doi.org/10.1080/00207454.2019.1711377.CrossRefPubMed

80.

Ballester P, Martínez MJ, Inda MD, Javaloyes A, Richdale AL, Muriel J, Belda C, Toral N, Morales D, Fernández E, Peiró AM. Evaluation of agomelatine for the treatment of sleep problems in adults with autism spectrum disorder and co-morbid intellectual disability. J Psychopharmacol. 2019;33(11):1395–406. https://doi.org/10.1177/0269881119864968.CrossRefPubMed

81.

Buckley AW, Sassower K, Rodriguez AJ, Jennison K, Wingert K, Buckley J, Thurm A, Sato S, Swedo S. An open label trial of donepezil for enhancement of rapid eye movement sleep in young children with autism spectrum disorders. J Child Adolesc Psychopharmacol. 2011;21(4):353–7. https://doi.org/10.1089/cap.2010.0121.CrossRefPubMedPubMedCentral

82.

Rossignol DA, Frye RE. The use of medications approved for Alzheimer’s disease in autism spectrum disorder: a systematic review. Front Pediatr. 2014;2:87. https://doi.org/10.3389/fped.2014.00087.CrossRefPubMedPubMedCentral

83.

Gabis LV, Ben-Hur R, Shefer S, Jokel A, Shalom DB. Improvement of language in children with autism with combined donepezil and choline treatment. J Mol Neurosci. 2019;69(2):224–34. https://doi.org/10.1007/s12031-019-01351-7.CrossRefPubMed

84.

Thirumalai SS, Shubin RA, Robinson R. Rapid eye movement sleep behavior disorder in children with autism. J Child Neurol. 2002;17(3):173–8. https://doi.org/10.1177/088307380201700304.CrossRefPubMed

85.

Mendez MA, Horder J, Myers J, Coghlan S, Stokes P, Erritzoe D, Howes O, Lingford-Hughes A, Murphy D, Nutt D. The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: a pilot [(11)C]Ro15-4513 positron emission tomography study. Neuropharmacology. 2013;68:195–201. https://doi.org/10.1016/j.neuropharm.2012.04.008.CrossRefPubMed

86.

Han S, Tai C, Jones CJ, Scheuer T, Catterall WA. Enhancement of inhibitory neurotransmission by GABAA receptors having α2,3-subunits ameliorates behavioral deficits in a mouse model of autism. Neuron. 2014;81(6):1282–9. https://doi.org/10.1016/j.neuron.2014.01.016.CrossRefPubMedPubMedCentral

87.

Zhu JW, Zou MM, Li YF, Chen WJ, Liu JC, Chen H, Fang LP, Zhang Y, Wang ZT, Chen JB, Huang W, Li S, Jia WQ, Wang QQ, Zhen XC, Liu CF, Li S, Xiao ZC, Xu GQ, Schwamborn JC, Schachner M, Ma QH, Xu RX. Absence of TRIM32 leads to reduced gabaergic interneuron generation and autism-like behaviors in mice via suppressing mTOR signaling. Cereb Cortex. 2020;30(5):3240–58. https://doi.org/10.1093/cercor/bhz306.CrossRefPubMed

88.

Naguy A, Pridmore S, Alamiri B. Benzodiazepines in autism spectrum disorder—wise or otherwise? CNS Spectr. 2021. https://doi.org/10.1017/S1092852921000481.CrossRefPubMed

89.

Ingrassia A, Turk J. The use of clonidine for severe and intractable sleep problems in children with neurodevelopmental disorders—a case series. Eur Child Adolesc Psychiatry. 2005;14(1):34–40. https://doi.org/10.1007/s00787-005-0424-4.CrossRefPubMed

90.

Wichniak A, Wierzbicka A, Jernajczyk W. Sleep and antidepressant treatment. Curr Pharm Des. 2012;18(36):5802–17. https://doi.org/10.2174/138161212803523608.CrossRefPubMed

91.

Posey DJ, Guenin KD, Kohn AE, Swiezy NB, McDougle CJ. A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2001;11(3):267–77. https://doi.org/10.1089/10445460152595586.CrossRefPubMed

92.

Blackmer AB, Feinstein JA. Management of sleep disorders in children with neurodevelopmental disorders: a review. Pharmacotherapy. 2016;36(1):84–98. https://doi.org/10.1002/phar.1686.CrossRefPubMed

93.

Ballester P, Richdale AL, Baker EK, Peiró AM. Sleep in autism: a biomolecular approach to aetiology and treatment. Sleep Med Rev. 2020;54: 101357. https://doi.org/10.1016/j.smrv.2020.101357.CrossRefPubMed

94.

Dosman CF, Brian JA, Drmic IE, Senthilselvan A, Harford MM, Smith RW, Sharieff W, Zlotkin SH, Moldofsky H, Roberts SW. Children with autism: effect of iron supplementation on sleep and ferritin. Pediatr Neurol. 2007;36(3):152–8. https://doi.org/10.1016/j.pediatrneurol.2006.11.004.CrossRefPubMed

95.

Bitsika V, Sharpley CF, Sweeney JA, McFarlane JR. HPA and SAM axis responses as correlates of self- vs parental ratings of anxiety in boys with an autistic disorder. Physiol Behav. 2014;127:1–7. https://doi.org/10.1016/j.physbeh.2013.12.011.CrossRefPubMed

96.

Tordjman S, Anderson GM, Bellissant E, Botbol M, Charbuy H, Camus F, Graignic R, Kermarrec S, Fougerou C, Cohen D, Touitou Y. Day and nighttime excretion of 6-sulphatoxymelatonin in adolescents and young adults with autistic disorder. Psychoneuroendocrinology. 2012;37(12):1990–7. https://doi.org/10.1016/j.psyneuen.2012.04.013.CrossRefPubMed

97.

Tordjman S, Davlantis KS, Georgieff N, Geoffray MM, Speranza M, Anderson GM, Xavier J, Botbol M, Oriol C, Bellissant E, Vernay-Leconte J, Fougerou C, Hespel A, Tavenard A, Cohen D, Kermarrec S, Coulon N, Bonnot O, Dawson G. Autism as a disorder of biological and behavioral rhythms: toward new therapeutic perspectives. Front Pediatr. 2015;3:1. https://doi.org/10.3389/fped.2015.00001.CrossRefPubMedPubMedCentral

98.

Tordjman S, Najjar I, Bellissant E, Anderson GM, Barburoth M, Cohen D, Jaafari N, Schischmanoff O, Fagard R, Lagdas E, Kermarrec S, Ribardiere S, Botbol M, Fougerou C, Bronsard G, Vernay-Leconte J. Advances in the research of melatonin in autism spectrum disorders: literature review and new perspectives. Int J Mol Sci. 2013;14(10):20508–42. https://doi.org/10.3390/ijms141020508.CrossRefPubMedPubMedCentral

99.

Amiet C, Gourfinkel-An I, Bouzamondo A, Tordjman S, Baulac M, Lechat P, Mottron L, Cohen D. Epilepsy in autism is associated with intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry. 2008;64(7):577–82. https://doi.org/10.1016/j.biopsych.2008.04.030 (Epub 2008 Jun 20).CrossRefPubMed

100.

Boucher J. Lost in a sea of time: time-parsing and autism. In: Hoerl C, McCormack T, editors. Time and memory. Oxford: Clarendon Press; 2001. p. 111–35.

101.

Wimpory D, Nicholas B, Nash S. Social timing, clock genes and autism: a new hypothesis. J Intellect Disabil Res. 2002;46(4):352–8. https://doi.org/10.1046/j.1365-2788.2002.00423.x.CrossRefPubMed

102.

Feldman R. Parent-infant synchrony and the construction of shared timing; physiological precursors, developmental outcomes, and risk conditions. J Child Psychol Psychiatry. 2007;48(3–4):329–54. https://doi.org/10.1111/j.1469-7610.2006.01701.x.CrossRefPubMed

103.

Fureix C, Benhajali H, Henry S, Bruchet A, Prunier A, Ezzaouia M, Coste C, Hausberger M, Palme R, Jego P. Plasma cortisol and faecal cortisol metabolites concentrations in stereotypic and non-stereotypic horses: do stereotypic horses cope better with poor environmental conditions? BMC Vet Res. 2013;9:3. https://doi.org/10.1186/1746-6148-9-3.CrossRefPubMedPubMedCentral

104.

Garstang J, Wallis M. Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child Care Health Dev. 2006;32(5):585–9. https://doi.org/10.1111/j.1365-2214.2006.00616.x.CrossRefPubMed

105.

Kaartinen M, Puura K, Mäkelä T, Rannisto M, Lemponen R, Helminen M, Salmelin R, Himanen SL, Hietanen JK. Autonomic arousal to direct gaze correlates with social impairments among children with ASD. J Autism Dev Disord. 2012;42(9):1917–27. https://doi.org/10.1007/s10803-011-1435-2.CrossRefPubMed

106.

Bal E, Harden E, Lamb D, Van Hecke AV, Denver JW, Porges SW. Emotion recognition in children with autism spectrum disorders: relations to eye gaze and autonomic state. J Autism Dev Disord. 2010;40(3):358–70. https://doi.org/10.1007/s10803-009-0884-3.CrossRefPubMed

107.

Bazelmans T, Jones EJH, Ghods S, Corrigan S, Toth K, Charman T, Webb SJ. Heart rate mean and variability as a biomarker for phenotypic variation in preschoolers with autism spectrum disorder. Autism Res. 2019;12(1):39–52. https://doi.org/10.1002/aur.1982.CrossRefPubMed

108.

Smeekens I, Didden R, Verhoeven EW. Exploring the relationship of autonomic and endocrine activity with social functioning in adults with autism spectrum disorders. J Autism Dev Disord. 2015;45(2):495–505. https://doi.org/10.1007/s10803-013-1947-z.CrossRefPubMed

109.

Carpita B, Marazziti D, Palego L, Giannaccini G, Betti L, Dell’Osso L. Microbiota, immune system and autism spectrum disorders: an integrative model towards novel treatment options. Curr Med Chem. 2020;27(31):5119–36. https://doi.org/10.2174/0929867326666190328151539.CrossRefPubMed

110.

Kong X, Liu J, Liu K, Koh M, Tian R, Hobbie C, Fong M, Chen Q, Zhao M, Budjan C, Kong J. Altered autonomic functions and gut microbiome in individuals with autism spectrum disorder (ASD): implications for assisting ASD screening and diagnosis. J Autism Dev Disord. 2021;51(1):144–57. https://doi.org/10.1007/s10803-020-04524-1.CrossRefPubMed

111.

Frank E, Cassano GB, Shear MK, Rotondo A, Dell’Osso L, Mauri M, et al. The spectrum model: a more coherent approach to the complexity of psychiatric symptomatology. CNS Spectr. 1998;3(4):23–34. https://doi.org/10.1017/S1092852900005836.CrossRef

112.

Dell’Osso L, Conversano C, Corsi M, Bertelloni CA, Cremone IM, Carpita B, Carbone MG, Gesi C, Carmassi C. Polysubstance and behavioral addictions in a patient with bipolar disorder: role of lifetime subthreshold autism spectrum. Case Rep Psychiatry. 2018;2018:1547975. https://doi.org/10.1155/2018/1547975.CrossRefPubMedPubMedCentral

113.

Dell’Osso L, Carpita B, Bertelloni CA, Diadema E, Barberi FM, Gesi C, Carmassi C. Subthreshold autism spectrum in bipolar disorder: prevalence and clinical correlates. Psychiatry Res. 2019;281: 112605. https://doi.org/10.1016/j.psychres.2019.112605.CrossRefPubMed

114.

Dell’Osso L, Lorenzi P, Carpita B. Autistic traits and illness trajectories. Clin Pract Epidemiol Ment Health. 2019;15:94–8. https://doi.org/10.2174/1745017901915010094.CrossRefPubMedPubMedCentral

115.

Dell’Osso L, Bertelloni CA, Di Paolo M, Avella MT, Carpita B, Gori F, Pompili M, Carmassi C. Problematic internet use in university students attending three superior graduate schools in Italy: is autism spectrum related to suicide risk? Int J Environ Res Public Health. 2019;16(7):1098. https://doi.org/10.3390/ijerph16071098.CrossRefPubMedCentral

116.

Dell’Osso L, Lorenzi P, Carpita B. The neurodevelopmental continuum towards a neurodevelopmental gradient hypothesis. J Psychopathol. 2019;25(4):179–82.

117.

Carpita B, Muti D, Muscarella A, Dell’Oste V, Diadema E, Massimetti G, Signorelli MS, Fusar Poli L, Gesi C, Aguglia E, Politi P, Carmassi C, Dell’Osso L. Sex differences in the relationship between PTSD spectrum symptoms and autistic traits in a sample of university students. Clin Pract Epidemiol Ment Health. 2019;15:110–9. https://doi.org/10.2174/1745017901915010110.CrossRefPubMedPubMedCentral

118.

Carpita B, Carmassi C, Calderoni S, Muti D, Muscarella A, Massimetti G, Cremone IM, Gesi C, Conti E, Muratori F, Dell’Osso L. The broad autism phenotype in real-life: clinical and functional correlates of autism spectrum symptoms and rumination among parents of patients with autism spectrum disorder. CNS Spectr. 2020;25(6):765–73. https://doi.org/10.1017/S1092852919001615.CrossRefPubMed

Title: Biological correlates of altered circadian rhythms, autonomic functions and sleep problems in autism spectrum disorder
Authors: Liliana Dell’Osso
Leonardo Massoni
Simone Battaglini
Ivan Mirko Cremone
Claudia Carmassi
Barbara Carpita
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Autism Spectrum Disorder
Published in: Annals of General Psychiatry / Issue 1/2022
Electronic ISSN: 1744-859X
DOI: https://doi.org/10.1186/s12991-022-00390-6

At a glance: The STEP trials

Springer Medicine

Biological correlates of altered circadian rhythms, autonomic functions and sleep problems in autism spectrum disorder

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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