PEDIATRICS Vol. 110 No. 4 October 2002, pp. 850-852
Attention-Deficit/Hyperactivity Disorder and Sleep
To the Editor.—As an epidemiologist who studies attention-deficit/hyperactivity disorder (ADHD), I read with great interest the recent report by Chervin et al1 on the association between symptoms of ADHD and sleep-disordered breathing (SDB). I am concerned, however, that their conclusions are preliminary and that the statistical analysis is potentially misleading.
In particular, the conclusion that from 15% to 39% of ADHD cases may be attributable to SDB cannot be justified at this time. This statistic, the population attributable risk percent, describes the proportion of cases in a population comprised of exposed and nonexposed individuals that is caused by the exposure of interest. As the authors point out, this requires that a causal link be established between exposure and disease. The presentation of this statistic is premature because it has not been established that SDB is causally related to symptoms of ADHD, and questions regarding the validity of the association reported by Chervin et al are raised by methodological limitations.
The authors indicate in the limitations section of their report that the association they found was cross-sectional and did not allow them to demonstrate if SDP preceded the symptoms of ADHD or vice versa. Establishing such a time sequence is a minimal criterion for demonstrating causality. Furthermore, the current state of knowledge regarding sleep problems in ADHD subjects is very sparse and is far from establishing a consistent pattern of results that could reasonably suggest that SDB is causally linked with ADHD or its symptoms. Thus, it was inappropriate to calculate and present the population attributable risk percent because there is no convincing evidence that SBD is causally related to symptoms of ADHD.
Methodological limitations also raise concerns regarding the validity of the associations reported by Chervin et al. The association between symptoms of ADHD and SBD is likely to be confounded by important factors that have been shown to modify the risk for sleeping problems in children with ADHD.2,3 Previous studies have shown that comorbidity with anxiety and other disruptive behavior disorders accounts for much of the sleep problems reported by children with ADHD. This research also shows that treatment of ADHD with stimulants impacts the relative risk of sleep problems reported in ADHD samples. Although psychiatric comorbidity and stimulant therapy may also confound association between symptoms of ADHD and SDB, Chervin et al addressed potential confounding by neither of these important factors. Because the estimates of relative risk are likely biased by lack of attention to known confounders, it was inappropriate to use them to calculate the population attributable risk percent.
Identifying the causal risk factors for ADHD and the proportion of cases that could be attributable to them is a very important endeavor and is in need of much more research. However, these measures need to be based upon valid estimates of increased risk drawn from a wide database of research if they are to have any impact on public health. If published prematurely, the population attributable risk percent will needlessly confuse clinicians and their patients and could interfere with the delivery of appropriate and better studied treatments.
Eric Mick, ScD
Department of Psychiatry
Massachusetts General Hospital and Harvard Medical School
Boston, MA 02114
REFERENCES
1. Chervin RD, Archbold KH, Dillon JE, et al. Inattention, hyperactivity, and symptoms of sleep-disordered breathing.
Pediatrics.2002; 109
:449
–456
2. Mick E, Biederman J, Jetton J, Faraone SV. Sleep disturbances associated with attention deficit hyperactivity disorder: the impact of psychiatric comorbidity and pharmacotherapy. J Child Adolesc Psyhopharmacol.2000; 10 :223 –231
3. Corkum P, Moldofsky H, Hogg-Johnson S, Humphries T, Tannock R. Sleep problems in children with attention-deficit/hyperactivity disorder: impact of subtype, comorbidity, and stimulant medication. J Am Acad Child Adolesc Psychiatry.1999; 38 :1285 –1293[CrossRef][Web of Science][Medline]
In Reply.—
In dismissing the likelihood that sleep-disordered breathing (SDB) does contribute to inattentive and hyperactive behavior (HB), Dr Mick ignores clinical and physiological data, overlooks literature on specific sleep disorders, focuses on nonspecific "sleep problems," and relies mainly on a lack of longitudinal epidemiological studies. Since the first modern description of SDB in children 26 years ago,1 published reports have consistently noted high frequencies of HB, as well as improvement in HB after treatment for SDB.2–5 Similar daytime behavior also is reported in several other primary sleep disorders, as is behavioral improvement after treatment for those conditions.6–10 In controlled experimental settings, sleep deprivation causes inattentive behavior and cognitive changes that could contribute to HB.11,12 Inattention and hyperactivity are described as important symptoms or consequences of SDB in current sleep textbooks,13,14 review articles,15–17 national academy courses,18 and American Academy of Pediatrics literature reviews19 and clinical practice guidelines.20 Many sleep researchers are now more interested in explaining how, rather than whether, sleep disorders change behavior and underlying cognitive processes.21 Animal models and functional imaging have already provided valuable clues.22,23 In short, abundant data provide convergent support, if not proof, for the less-than-astonishing hypothesis that interruption of normal brain function during the one third of a child’s existence spent asleep does have important ramifications on brain function during the remaining two thirds.
In this context, our recent article24 was conservative and reserved rather than premature or misleading. We were careful to point out that our own data do not prove SDB causes HB. We discussed the possibility of a causal relationship only among other potential explanations for the association we identified. We were careful not to imply a causal relationship in the title of the manuscript, an all too common phenomenon even when the study design used precludes definitive identification of cause-and-effect relationships.25,26
The concerns expressed about our methods neglect important considerations from both clinical and epidemiological standpoints. Considerable biological overlap exists among disruptive behavior disorders, and sleep disorders are believed to influence a number of psychiatric conditions in addition to HB, including anxiety.17 To have adjusted our results for behavioral outcomes comorbid with HB most likely would have resulted in overadjustment, reducing the apparent association between SDB symptoms and HB for reasons that are artificial rather than valid. Adjustment for stimulant use was not necessary: a confounder must be associated both variables in a relationship, and a physiological explanation for how stimulants would increase snoring is not known or readily imaginable. In any case, our previous work showed that adjustment for stimulant use does not eliminate the association between SDB symptoms and HB.27 Perhaps Dr Mick was misled by results of his own research, which focused exclusively on sleep-related behavioral issues: sleep walking, dream anxiety, sleep terrors, and 19 nonspecific "sleep problems" such as going to bed willingly, waking up at night, falling asleep easily, fear of sleeping in the dark, talking about pleasant dreams, and smiling while asleep.25 The unsurprising conclusion that most of these behavioral problems showed stronger associations with anxiety and stimulants than with ADHD yields no information pertinent to sleep-disordered breathing—which was not mentioned or assessed—and hardly identifies "known confounders" of the results we reported. Authors of a previous, similar study of ADHD correlates were careful to point out that their research did not address SDB.28
The concerns about our use of the population attributable risk percent (PARP) confuse what we reported. First, the PARP for the entire sample of 866 children was 15%; the higher figure (39%) applied only to the specific subgroup of 295 boys younger than 8 years old. Second, we did not study ADHD cases, but rather HB as assessed by 2 well-validated measures. The PARP was not mentioned in the abstract, overemphasized as the main finding, or discussed without redundant reminders that it is contingent on the belief that SDB can contribute to HB. Most clinicians interested in childhood sleep disorders already believe that SDB can promote HB, at least in some cases. Otolaryngologists, for example, frequently consider attention deficit to be an indication for adenotonsillectomy, a common treatment for childhood SDB.29 We presented the PARP with exceptional care so that readers could make an informed decision about its validity, based on their own level of conviction about an underlying cause-and-effect relationship.
As already emphasized in our article,24 we agree that more work is needed to prove, quantify, and better define a causal link between SDB and HB. Such work may profit considerably from increased collaboration between epidemiologists and sleep specialists. Our work, including the PARP we calculated, helps to quantify the reward that may accrue from such efforts and thereby helps to motivate needed research. As explained by Dr Mick himself, in an article published only 1 month before our own, "Even in the absence of a conclusive causal link, estimating how many cases could be attributable to a specific risk factor is often valuable in focusing research and clinical resources."26
Ronald D. Chervin, MD, MS
Sleep Disorders Center
Department of Neurology
University of Michigan, Ann Arbor, MI 48109-0117
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29. Weatherly RA, Mai EF, Ruzicka DL, Chervin RD. Adenotonsillectomy in children: indications, practices, and outcomes reported by otolaryngologists. Sleep.2000; 24(suppl) :A212 –A213
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
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