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Volume 12 No. 06
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Accepted Papers

Letters to the Editor

A Reply to Sleep Characteristics in Children with Attention Deficit Hyperactivity Disorder: Systematic Review and Meta-Analyses by Díaz-Román et al.

Keith Fluegge, PhD
Institute of Health and Environmental Research, Cleveland, OH

Díaz-Román, Hita-Yáñez, and Buela-Casal have clarified the association between sleep disturbances and attention deficit hyperactivity disorder (ADHD). In the studies assessing polysomnographic outcomes, the authors reported a main finding that children with ADHD spent significantly more time in stage 1 sleep than did controls.1 In an earlier report in JCSM, Ratnavadivel et al.2 characterized obstructive sleep apnea (OSA) with a delay to slow wave sleep (significant increase in both time spent and proportion of total sleep time in stage 1 sleep), suggesting that OSA may be a feature of ADHD. Indeed, a systematic review of the literature does indicate that attentional deficits and OSA may be linked.3

Recently, it has been posited that chronic exposure to trace amounts of the environmental air pollutant, nitrous oxide (N2O), may be a precipitating factor in the development of cognitive deficits that are represented in ADHD (i.e., working memory).4 The association between ADHD and comorbidities, like mild traumatic brain injury (mTBI), may therefore exist due to the toxicological synergisms from the underlying etiologies of these conditions (i.e., environmental exposure to N2O for ADHD and alcohol/drug abuse for mTBI).4

Interestingly, exposure to 50% N2O in O2 in healthy adult males resulted in a sleep-apnea syndrome, characterized by a reduced sleep latency to stage 2 and an overall deeper sleep.5 However, arousal-induced sleep disruptions arose more often with the lower concentration of N2O (30%) used in the study, and these disruptions occurred more during stage 1.5 As cortical arousal is a diagnostic feature of ADHD,6 these results support the hypothesis that very low level of exposure to environmental N2O may predispose a state of cortical arousal that is characteristic of ADHD while concomitantly inducing sleep disruptions in stage 1.

These results suggest that chronic exposure to increasing amounts of environmental N2O may be an etiologic factor in the development of ADHD. This correspondence offers another dimension of this hypothesis insofar as the cognitive impairment from N2O exposure may exert a compensatory cortical hyperarousal via modulation of neurotransmission that disrupts sleep patterns in ADHD.


Mr. Fluegge has indicated no financial conflicts of interest.


Fluegge K. A reply to sleep characteristics in children with attention deficit hyperactivity disorder: systematic review and meta-analyses by Díaz-Román et al. J Clin Sleep Med 2016;12(6):933.



Díaz-Román A, Hita-Yáñez E, Buela-Casal G, authors. Sleep characteristics in children with attention deficit hyperactivity disorder: systematic review and meta-analyses. J Clin Sleep Med. 2016;12:747–56. [PubMed]


Ratnavadivel R, Chau N, Stadler D, Yeo A, McEvoy RD, Catcheside PG, authors. Marked reduction in obstructive sleep apnea severity in slow wave sleep. J Clin Sleep Med. 2009;5:519–24. [PubMed Central][PubMed]


Youssef NA, Ege M, Angly SS, Strauss JL, Marx CE, authors. Is obstructive sleep apnea associated with ADHD? Ann Clin Psychiatry. 2011;23:213–24. [PubMed]


Fluegge K, author. Do toxic synergies of underlying etiologies predispose the positive association between traumatic brain injury and ADHD? J Atten Disord. 2016 Mar 8. [Epub ahead of print]. [PubMed Central]


Beydon L, Goldenberg F, Heyer L, d'Ortho MP, Bonnet F, Harf A, Lofaso F, authors. Sleep apnea-like syndrome induced by nitrous oxide inhalation in normal men. Respir Physiol. 1997;108:215–24. [PubMed]


Loo SK, Hale TS, Macion J, et al., authors. Cortical activity patterns in ADHD during arousal, activation and sustained attention. Neuropsychologia. 2009;47:2114–9. [PubMed Central][PubMed]