Insomnia symptoms, objective sleep duration and hypothalamic-pituitary-adrenal activity in children
Julio Fernandez-Mendoza
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorCorresponding Author
Alexandros N. Vgontzas
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Correspondence to: Alexandros N. Vgontzas, MD, Department of Psychiatry H073, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Tel.: (717) 531 7278; fax: (717) 531 6491; e-mail: [email protected]Search for more papers by this authorSusan L. Calhoun
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorAngeliki Vgontzas
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorMarina Tsaoussoglou
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorJordan Gaines
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorDuanping Liao
Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorGeorge P. Chrousos
First Department of Pediatrics and Unit of Endocrinology, Metabolism and Diabetes, University of Athens, Athens, Greece
Search for more papers by this authorEdward O. Bixler
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorJulio Fernandez-Mendoza
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorCorresponding Author
Alexandros N. Vgontzas
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Correspondence to: Alexandros N. Vgontzas, MD, Department of Psychiatry H073, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Tel.: (717) 531 7278; fax: (717) 531 6491; e-mail: [email protected]Search for more papers by this authorSusan L. Calhoun
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorAngeliki Vgontzas
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorMarina Tsaoussoglou
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorJordan Gaines
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorDuanping Liao
Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorGeorge P. Chrousos
First Department of Pediatrics and Unit of Endocrinology, Metabolism and Diabetes, University of Athens, Athens, Greece
Search for more papers by this authorEdward O. Bixler
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, PA, USA
Search for more papers by this authorAbstract
Background
Insomnia symptoms are the most common parent-reported sleep complaints in children; however, little is known about the pathophysiology of childhood insomnia symptoms, including their association with hypothalamic-pituitary-adrenal (HPA) axis activation. The objective of this study is to examine the association between parent-reported insomnia symptoms, objective short sleep duration and cortisol levels in a population-based sample of school-aged children.
Design
A sample of 327 children from the Penn State Child Cohort (5–12 years old) underwent 9-h overnight polysomnography and provided evening and morning saliva samples to assay for cortisol. Objective short sleep duration was defined based on the median total sleep time (i.e., < 7·7 h). Parent-reported insomnia symptoms of difficulty initiating and/or maintaining sleep were ascertained with the Pediatric Behavior Scale.
Results
Children with parent-reported insomnia symptoms and objective short sleep duration showed significantly increased evening (0·33 ± 0·03 μg/dL) and morning (1·38 ± 0·08 μg/dL) cortisol levels. In contrast, children with parent-reported insomnia symptoms and ‘normal’ sleep duration showed similar evening and morning cortisol levels (0·23 ± 0·03 μg/dL and 1·13 ± 0·08 μg/dL) compared with controls with ‘normal’ (0·28 ± 0·02 μg/dL and 1·10 ± 0·04 μg/dL) or short (0·28 ± 0·02 μg/dL and 1·13 ± 0·04 μg/dL) sleep duration.
Conclusions
Our findings suggest that insomnia symptoms with short sleep duration in children may be related to 24-h basal or responsive physiological hyperarousal. Future studies should explore the association of insomnia symptoms with short sleep duration with physical and mental health morbidity.
References
- 1Smedje H, Broman JE, Hetta J. Parents' reports of disturbed sleep in 5–7-year-old Swedish children. Acta Paediatr 1999; 88: 858–65.
- 2Liu X, Sun Z, Uchiyama M, Shibui K, Kim K, Okawa M. Prevalence and correlates of sleep problems in Chinese schoolchildren. Sleep 2000; 23: 1053–62.
- 3Stein MA, Mendelsohn J, Obermeyer WH, Amromin J, Benca R. Sleep and behavior problems in school-aged children. Pediatrics 2001; 107: E60.
- 4Spruyt K, O'Brien LM, Cluydts R, Verleye GB, Ferri R. Odds, prevalence and predictors of sleep problems in school-age normal children. J Sleep Res 2005; 14: 163–76.
- 5Fricke-Oerkermann L, Pluck J, Schredl M, Heinz K, Mitschke A, Wiater A et al. Prevalence and course of sleep problems in childhood. Sleep 2007; 30: 1371–7.
- 6Singareddy R, Moole S, Calhoun S, Vocalan P, Tsaoussoglou M, Vgontzas AN et al. Medical complaints are more common in young school-aged children with parent reported insomnia symptoms. J Clin Sleep Med 2009; 5: 549–53.
- 7Calhoun SL, Fernandez-Mendoza J, Vgontzas AN, Liao D, Bixler EO. Prevalence of insomnia symptoms in a general population sample of young children and preadolescents: gender effects. Sleep Med 2014; 15: 91–95.
- 8 American Academy of Sleep Medicine. The International Classification of Sleep Disorders: Diagnostic and Coding Manual, 2nd Edn. Westchester: American Academy of Sleep Medicine; 2005.
- 9Vgontzas AN, Tsigos C, Bixler EO, Stratakis CA, Zachman K, Kales A et al. Chronic insomnia and activity of the stress system: a preliminary study. J Psychosom Res 1998; 45: 21–31.
- 10Vgontzas AN, Bixler EO, Lin HM, Prolo P, Mastorakos G, Vela-Bueno A et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J Clin Endocrinol Metab 2001; 86: 3787–94.
- 11Monroe LJ. Psychological and physiological differences between good and poor sleepers. J Abnorm Psychol 1967; 72: 255–64.
- 12Johns MW, Gay TJA, Masterton JP, Bruce DW. Relationship between habits, adrenocortical activity and personality. Psychosom Med 1971; 33: 499–508.
- 13Adam K, Tomeny M, Oswald I. Physiological and psychological differences between good and poor sleepers. J Psychiatr Res 1986; 20: 301–16.
- 14Rodenbeck A, Huether G, Ruther E, Hajak G. Interactions between evening and nocturnal cortisol secretion and sleep parameters in patients with severe chronic primary insomnia. Neurosci Lett 2002; 324: 159–63.
- 15Shaver JL, Johnston SK, Lentz MJ, Landis CA. Stress exposure, psychological distress, and physiological stress activation in midlife women with insomnia. Psychosom Med 2002; 64: 793–802.
- 16Rodenbeck A, Cohrs S, Jordan W, Huether G, Rüther E, Hajak G. The sleep-improving effects of doxepin are paralleled by a normalized plasma cortisol secretion in primary insomnia. A placebo-controlled, double-blind, randomized, cross-over study followed by an open treatment over 3 weeks. Psychopharmacology 2003; 170: 423–8.
- 17Varkevisser M, Van Dongen HP, Kerkhof GA. Physiologic indexes in chronic insomnia during a constant routine: evidence for general hyperarousal? Sleep 2005; 28: 1588–96.
- 18Bonnet MH. Hyperarousal as the basis for insomnia: effect size and significance. Sleep 2005; 28: 1500–1.
- 19Irwin M, Clark C, Kennedy B, Christian Gillin J, Ziegler M. Nocturnal catecholamines and immune function in insomniacs, depressed patients, and control subjects. Brain Behav Immun 2003; 17: 365–72.
- 20Bonnet MH, Arand DL. 24-Hour metabolic rate in insomniacs and matched normal sleepers. Sleep 1995; 18: 581–8.
- 21Nofzinger EA, Nissen C, Germain A, Moul D, Hall M, Price JC et al. Regional cerebral metabolic correlates of WASO during NREM sleep in insomnia. J Clin Sleep Med 2006; 2: 316–22.
- 22Stepanski E, Glinn M, Zorick F, Roehrs T, Roth T. Heart rate changes in chronic insomnia. Stress Med 1994; 10: 261–6.
- 23Bonnet MH, Arand DL. Heart rate variability in insomniacs and matched normal sleepers. Psychosom Med 1998; 60: 610–5.
- 24Spiegelhalder K, Fuchs L, Ladwig J, Kyle SD, Nissen C, Volderholzer U et al. Heart rate and heart rate variability in subjectively reported insomnia. J Sleep Res 2010; 20: 137–45.
- 25Lichstein K, Johnson RS. Pupillometric discrimination of insomniacs. Behav Res Ther 1994; 32: 123–9.
- 26Riemann D, Klein T, Rodenbeck A, Feige B, Horny A, Hummel R et al. Nocturnal cortisol and melatonin secretion in primary insomnia. Psychiatry Res 2002; 113: 17–27.
- 27El-Sheikh M, Buckhalt JA, Keller PS, Granger DA. Children's objective and subjective sleep disruptions: links with afternoon cortisol levels. Health Psychol 2008; 27: 26–33.
- 28Räikkönen K, Matthews KA, Pesonen AK, Pyhälä R, Paavonen EJ, Feldt K et al. Poor sleep and altered hypothalamic-pituitary-adrenocorticol and sympatho-adrenal-medullary system activity in children. J Clin Endocrinol Metab 2010; 95: 2254–61.
- 29Pesonen AK, Kajantie E, Heinonen K, Pyhälä R, Lahti J, Jones A et al. Sex-specific associations between sleep problems and hypothalamic-pituitary-adrenocortical axis activity in children. Psychoneuroendocrinology 2012; 37: 238–48.
- 30Bixler EO, Vgontzas AN, Lin HM, Liao D, Calhoun S, Fedok F et al. Blood pressure associated with sleep-disordered breathing in a population sample of children. Hypertension 2008; 52: 841–6.
- 31Bixler EO, Vgontzas AN, Lin HM, Liao D, Calhoun S, Vela-Bueno A et al. Sleep disordered breathing in children in a general population sample: prevalence and risk factors. Sleep 2009; 32: 731–6.
- 32Lindgren SD, Koeppl GK. Assessing child behavior problems in a medical setting: development of the Pediatric Behavior Scale. In: RJ Prinz, editor. Advances in Behavioral Assessment of Children and Families. Greenwich: JAI; 1987: pp 57–90.
- 33 American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir Crit Care Med 1996; 153: 866–78.
- 34 National Heart, Lung, and Blood Institute Obesity Education Initiative Expert Panel. The practical guide: Identification, evaluation and treatment of overweight and obesity in adults. 2000; NIH publication 00-4084. Available at: http://www.nhlbi.nih.gov/guidelines/obesity/prctgd_c.pdf. Accessed on 1 November 2013.
- 35Hatzinger M, Brand S, Perren S, Stadelmann S, von Wyl A, von Klitzing K et al. Electroencephalographic sleep profiles and hypothalamic-pituitary-adrenocortical (HPA)-activity in kindergarten children: early indication of poor sleep quality associated with increased cortisol secretion. J Psychiatr Res 2008; 42: 532–43.
- 36Hatzinger M, Brand S, Perren S, Stadelmann S, von Wyl A, von Klitzing K et al. Sleep actigraphy pattern and behavioral/emotional difficulties in kindergarten children: association with hypothalamic-pituitary-adrenal (HPA) activity. J Psychiatric Res 2009; 44: 253–61.
- 37Scher A, Hall WA, Zaidman-Zait A, Weinberg J. Sleep quality, cortisol levels, and behavioral regulation in toddlers. Dev Psychobiol 2010; 52: 44–53.
- 38Gribbin CE, Watamura SE, Cairns A, Harsh JR, Lebourgeois MK. The cortisol awakening response (CAR) in 2- to 4-year-old children: effects of acute nighttime sleep restriction, wake time, and daytime napping. Dev Psychobiol 2012; 54: 412–22.
- 39Bonnet MH, Arand DL. Hyperarousal and insomnia: state of the science. Sleep Med Rev 2010; 14: 9–15.
- 40Vgontzas AN, Fernandez-Mendoza J, Liao D, Bixler EO. Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Sleep Med Rev 2013; 17: 241–54.
- 41Frankel BL, Buchbinder R, Coursey R, Snyder F. Sleep patterns and psychological test characteristics of chronic primary insomniacs. Sleep Res 1973; 2: 149.
- 42Freedman RR, Sattler HL. Physiological and psychological factors in sleep onset insomnia. J Abnorm Psychol 1982; 91: 380–9.
- 43Bonnet MH, Arand DL. Physiological activation in patients with sleep state misperception. Psychosom Med 1997; 59: 533–40.
- 44Lichstein KL, Johnson RS, Sen Gupta S, O'Laughlin DL, Dykstra TA. Are insomniacs sleepy during the day? A pupillometric assessment Behav Res Ther 1992; 30: 283–92.
- 45Lichstein KL, Wilson NM, Noe SL, Aguillard RN, Bellur SN. Daytime sleepiness in insomnia: behavioral, biological and subjective indices. Sleep 1994; 17: 693–702.
- 46Drake CL, Roth T. Predisposition in the evolution of insomnia: evidence, potential mechanisms and future direction. Sleep Med Clin 2006; 1: 333–49.
10.1016/j.jsmc.2006.06.005 Google Scholar
- 47Forbes EE, Williamson DE, Ryan ND, Birmaher B, Axelson DA, Dahl RE. Peri-sleep-onset cortisol levels in children and adolescents with affective disorders. Biol Psychiatry 2006; 59: 24–30.
- 48Vgontzas AN, Liao D, Bixler EO, Chrousos GP, Vela-Bueno A. Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep 2009; 32: 491–7.
- 49Fernandez-Mendoza J, Vgontzas AN, Liao D, Shaffer ML, Vela-Bueno A, Basta M et al. Insomnia with objective short sleep duration and incident hypertension: the Penn State Cohort. Hypertension 2012; 60: 929–35.
- 50Vgontzas AN, Liao D, Pejovic S, Calhoun S, Karataraki M, Bixler EO. Insomnia with objective short sleep duration is associated with type 2 diabetes: a population-based study. Diabetes Care 2009; 32: 1980–5.
- 51Fernandez-Mendoza J, Calhoun S, Bixler EO, Pejovic S, Karataraki M, Liao D et al. Insomnia with objective short sleep duration is associated with deficits in neuropsychological performance: a general population study. Sleep 2010; 33: 459–65.
- 52Fernandez-Mendoza J, Calhoun S, Bixler EO, Karataraki M, Liao D, Vela-Bueno A et al. Sleep misperception and chronic insomnia in the general population: role of objective sleep duration and psychological profiles. Psychosom Med 2011; 73: 88–97.
- 53Troxel WM, Kupfer DJ, Reynolds CF 3rd, Frank E, Thase ME, Miewald JM et al. Insomnia and objectively measured sleep disturbances predict treatment outcome in depressed patients treated with psychotherapy or psychotherapy-pharmacotherapy combinations. J Clin Psychiatry 2012; 73: 478–85.
- 54Vgontzas AN, Liao D, Pejovic S, Calhoun S, Karataraki M, Basta M et al. Insomnia with short sleep duration and mortality: the Penn State cohort. Sleep 2010; 33: 1159–64.
- 55Backhaus J, Junghanns K, Hohagen F. Sleep disturbances are correlated with decreased morning awakening salivary cortisol. Psychoneuroendocrinology 2004; 29: 1184–91.
