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Volume 09 No. 11
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Review Articles

The Relationship between Depressive Symptoms and Obstructive Sleep Apnea in Pediatric Populations: A Meta-Analysis

http://dx.doi.org/10.5664/jcsm.3178

Elif Yilmaz, M.D.1; Karim Sedky, M.D., M.Sc., F.A.A.S.M.2; David S. Bennett, Ph.D.1
1Department of Child and Adolescent Psychiatry, Drexel University College of Medicine, Philadelphia, PA; 2Department of Psychiatry, Cooper Medical School at Rowan University, Camden, NJ

ABSTRACT

Background:

A higher incidence of depressive disorders and symptoms has been suggested among children suffering from obstructive sleep apnea (OSA). Yet, the extent to which OSA is related to increased depression is unclear.

Objectives:

To evaluate (a) the relationship between depressive symptoms and OSA in pediatric populations, and (b) the efficacy of adenotonsillectomy (AT) for decreasing depressive symptoms among children with OSA.

Methods:

A meta-analysis was conducted to assess the relationship between depressive symptoms and OSA, and the efficacy of AT for decreasing depressive symptoms. Studies reporting depressive symptoms of children with OSA through January 2013 were included.

Results:

Eleven studies assessed depressive symptoms in both children diagnosed with OSA (n = 894) and a comparison group (n = 1,096). A medium relationship was found between depressive symptoms and OSA (Hedges' g = 0.43, 95% CI: 0.22-0.64; p = 0.0005). Addressing the second question, 9 studies (n = 379 children) examined depressive symptoms pre- and post-AT. A medium improvement in depressive symptoms was found at follow-up (Hedge's g = 0.41, 95% CI: 0.20-0.62; p ≤ 0.001).

Conclusion:

Our findings suggest that depressive symptoms are higher among children with OSA. Therefore, patients with depressive symptomatology should receive screening for sleep disordered breathing. Treatment of OSA with AT might decrease clinical symptoms of depression, reduce pharmacotherapy, improve sleep patterns, and promote better health.

Citation:

Yilmaz E; Sedky K; Bennett DS. The relationship between depressive symptoms and obstructive sleep apnea in pediatric populations: a meta-analysis. J Clin Sleep Med 2013;9(11):1213-1220.


Childhood depression is a significant problem that may lead to elevated psychosocial problems and physical disabilities.1 Adolescents with depression have an added risk of suicide and substance abuse.1 Subclinical depressive symptoms have also been associated with similar health problems including, poor quality of life, smoking and substance abuse, and future clinical depression.24 Depression affects approximately 1% of preschoolers, 2% of school-aged children, and 5% to 8% of adolescents in community samples and is a risk factor for noncompliance with medical treatment.5,6

Sleep disordered breathing (SDB) in children represents a spectrum of disorders ranging in severity from primary snoring to more severe forms such as obstructive sleep apnea (OSA).7 OSA, which is best assessed by full-night polysomnography, affects up to 2% of children, while subtle “subclinical” forms of SDB may affect many more.79 Although OSA is thought to be equally prevalent among both genders in childhood, the incidence of OSA increases gradually during adolescence when it becomes more common among males.10

In the adult literature, inconsistencies about the relation between depression and OSA exist. For example, Guilleminault et al. reported a high rate of depressive and anxiety symptoms (24%) among adults with OSA.11 In contrast, some studies did not find such a relation. Bardwell and colleagues, for example, reported that the relation between depressive symptoms and OSA was no longer significant after controlling for age, body mass index (BMI), and hypertension.12 The child literature is similarly inconsistent. Differences in diagnostic methods and criteria to identify OSA and its severity, as well as differences in how depressive symptoms are assessed, may affect the magnitude of the effect size (ES) between depressive symptoms and OSA.

Due to the inconsistent relationship between depressive symptoms and OSA, further research is needed to address the extent to which these problems are related. Enhanced understanding of the relationship between depressive symptoms and OSA may have important clinical implications. The use of antidepressant medications in children is controversial as they have limited efficacy,13 adverse events are common,14 and as a result medications are often considered only for severe cases or in those with a partial or non-response to therapy. At least in a subpopulation of children and adolescents presenting with depressive symptoms, screening for OSA may suggest alternative causes and treatment of depressive symptoms, preventing significant distress, disability, and financial loss. As the most common cause of OSA in children is enlargement of adenoids and/or tonsils, the first line of treatment involves adenotonsillectomy (AT),15 which might lead to significant decreases in depressive symptoms for those with OSA.

Using meta-analysis, we sought to examine (a) the strength of the relationship between depressive symptoms and OSA in children and adolescents, and (b) the effectiveness of AT on reducing depressive symptoms for children and adolescents with OSA.

METHODS

Study Selection

The PubMed/Medline, PsychInfo, Cochrane library, and Google Scholar data bases were searched using the terms “adenotonsillectomy,” “sleep disordered breathing,” “SDB,” “obstructive sleep apnea,” “OSA” and “depression,” “depressive symptoms,” “mood,” crossed by “child,” “children,” and “adolescents.” English-language studies through January 2013 were examined.

Inclusion and Exclusion Criteria

Selection of the articles was conducted by the first author (EY) and revised by the second (KS). Coded information included: sample size, age, gender, BMI, and study quality using the Newcastle-Ottawa scale.16 Studies of patients up to age 18 years were included in the meta-analysis (0-18 years old; no study was included if the oldest individual was older than 18).

Although there are several proposed methods to diagnose OSA, the gold standard diagnostic test remains polysomnography (PSG).17 Thus, in addressing our first question (i.e., the extent of a relationship between depressive symptoms and OSA), studies needed to include both PSG and a depression assessment measure in both the OSA and comparison groups. Twenty-two published studies were initially identified: 11 were excluded: 4 due to lack of the use of PSG to detect OSA (one lacked PSG in the control group18),1922 4 for the absence of a depression measure,2326 1 lacked a comparison group,27 and 1 was excluded due to division of groups into snorers versus non-snorers, without assessing for OSA.28 Eleven studies satisfied the inclusion criteria.1,2938 To avoid publication bias, our team searched for unpublished data including dissertations. Two unpublished dissertations were found; one was excluded due to the lack of a depression measure,39 and the other for the lack of PSG.40 Of the 11 included studies, 8 were dependent on the parent/caregiver to complete the forms, of which 4 also included teacher ratings of depressive symptoms. Three studies used child reports of depressive symptoms (see Table 1). Examining specific measures, 7 studies used the Child Behavior Checklist (CBCL), 2 of which also used the Teacher Report Form (TRF). Three other studies used the Children's Depression Inventory (CDI), and one used the Behavior Assessment Scale for Children (BASC).

Demographic information by group and the scale used

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Table 1

Demographic information by group and the scale used

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In the second part of the study, we examined whether depressive symptoms improved following AT. The follow-ups were conducted between 1.5 and 6 months post-surgery. Seventeen articles were identified, of which 9 were included in the meta-analysis.18,34,4147 Of the 8 excluded studies, 2 were excluded due to lack of PSG,48,49 one for the use of respiratory sinus arrhythmia rather than PSG,50 and 5 due to lack of a depression measure.5155 In all 9 included studies, parents/caregivers were the source of children's depressive symptom ratings, with one also including teacher ratings. Four studies used the CBCL and 5 used the BASC.

Data Analysis

All statistics included mean values with their standard deviation (SD). Data were analyzed using the Comprehensive Meta-Analysis, version 2.0 (Biostat, Englewood, NJ) software program. ES was calculated using Hedges' g and a random effects model, as is appropriate when there is heterogeneity in methodology among analyzed studies. Depressive symptom scores were compared between OSA and comparison groups in the first part, while pre- and post-adenotonsillectomy depressive symptom levels were compared in the second part of the study.

RESULTS

In the first part of the study, 11 studies were included; a total of 894 children in the OSA group and 1,096 in the comparison group. After excluding one study in each group that did not report gender data, the overall percentage of males was 57.83% (447/773) in the OSA group and 47.98% (476/992) in the comparison group. The mean unweighted age for the 10 studies in the OSA group was 8.85 ± 2.63 years, compared to 8.92 ± 2.38 for the comparison group.

Question 1: Is there an elevated rate of depressive symptoms in children with OSA compared to those without?

A significant relationship between depressive symptoms and OSA was found. Hedges' g was 0.43 (95% CI = 0.22-0.64; p = 0.00005; see Figure 1), indicating a medium relationship.56 Testing for heterogeneity, the Q value with 10 d.f. was 20.46, signifying mild heterogeneity across studies, while I2 was 51.13, p = 0.03, indicating moderate inconsistency among studies. When excluding one study that included children previously diagnosed with attention deficit hyperactivity disorder,34 the overall ES remained similar; 0.39 (95% CI = 0.18-0.60; p = 0.0002; see Figure 1). Testing for heterogeneity, the Q value with 9 d.f. was 17.39, again signifying mild heterogeneity across studies, while I2 was 48.24, p = 0.04. In addition, Kendall's tau = 0.05; this suggests that the standard errors of the means and the effect sizes were independent, indicating that there was not significant publication bias. To examine the ES of depressive symptoms separately in children with OSA versus those with primary snoring (PS), 4 studies were identified that included both OSA and primary snoring groups.29,32,37,57 While 3 of these studies used as criteria the presence of snoring and an AHI < 1 to diagnose PS, Crabtree and colleagues used a criteria of “mild OSA” for their snoring group. A nonsignificant ES was found in comparing children with OSA to those with PS (Hedges' g = 0.04, p = 0.76, Figure 2), indicating that depressive symptoms are similarly elevated among children with PS as well as OSA. This was consistent after including only the 3 studies that satisfied the strict criteria of PS (Hedges' g = 0.06, p = 0.73).

The relationship between OSA and depression

Group A represents the OSA group, while group B represents the depression group. *Groups having sleep disordered breathing (which is OSA with primary snoring) not only OSA. OSA, obstructive sleep apnea; LL, lower limit; UL, upper limit.

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Figure 1

The relationship between OSA and depression. Group A represents the OSA group, while group B represents the depression group. *Groups having sleep disordered breathing (which is OSA with primary snoring) not only OSA. OSA, obstructive sleep apnea; LL, lower limit; UL, upper limit.

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Difference in effect size between children with OSA and children with PS

OSA group are patients diagnosed with OSA, while PS group are children with primary snoring. OSA, obstructive sleep apnea; PS, primary snoring; LL, lower limit; UL, upper limit; Dep Sx, depressive symptoms.

jcsm.9.11.1213b.jpg

jcsm.9.11.1213b.jpg
Figure 2

Difference in effect size between children with OSA and children with PS. OSA group are patients diagnosed with OSA, while PS group are children with primary snoring. OSA, obstructive sleep apnea; PS, primary snoring; LL, lower limit; UL, upper limit; Dep Sx, depressive symptoms.

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While the relatively small number of studies limited our ability to identify significant moderators of the relation between depressive symptoms and OSA, we did explore several potential moderators using the mean weighted ESs. Gender was found to be a significant moderator as studies having a higher percentage of males had higher ESs (beta = 0.66, p = 0.03). Thus, the relationship between depressive symptoms and OSA appears to be stronger for boys than for girls. None of the other potential moderators were significant: average group age (beta = 0.07, p = 0.83), BMI (beta = -0.31, p = 0.43), or study quality (beta = 0.47; p = 0.13).

Question 2: Do depressive symptoms decrease following adenotonsillectomy?

In the second part of the study, 379 children across nine studies were assessed for depressive symptoms both pre- and post-surgery. Demographics of this group are presented in Table 2. The overall ES change between pre- versus post-surgery was 0.41 (95% CI = 0.20-0.62; p ≤ 0.001; see Figure 3), indicating a medium improvement56 occurred in depressive symptoms after AT. Testing for heterogeneity, the Q value with 8 d.f. was 16.11, again signifying mild heterogeneity across studies, while I2 was 50.34, p = 0.04, indicating moderate inconsistencies between studies. Of the 9 studies, 7 studies found ESs greater in the post-AT period compared to pre-surgery (ES = 0.54; p ≤ 0.001). One study found a negative effect size (ES = -0.94, 99% CI = -1.98-0.10; p = 0.08), while another found essentially no improvement following surgery (ES = -0.07; Figure 3). Of note, the largest ESs tended to be observed in studies that did not have a comparison group. Among the 3 studies that did have a comparison group, one showed mild improvement in the AT group compared to controls, the second showed no change, while the third showed worsening of symptoms after AT.

Demographic information of the clinical group undergoing adenotonsillectomy (AT) pre- and post-surgery

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Table 2

Demographic information of the clinical group undergoing adenotonsillectomy (AT) pre- and post-surgery

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Pre- and post-adenotonsillectomy depression/anxiety

LL, lower limit; UL, upper limit.

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Figure 3

Pre- and post-adenotonsillectomy depression/anxiety. LL, lower limit; UL, upper limit.

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DISCUSSION AND CONCLUSION

This study found a medium relation between depressive symptoms in children with OSA, with an ES of 0.45. This relationship was moderated by gender, as males showed a stronger relationship between depressive symptoms and OSA. In addition, children were found to exhibit fewer depressive symptoms after AT compared to pre-surgery, with an ES of 0.41. In the TuCASA study, 63 children suffering from RDI in the higher 15% were compared to 340 children suffering from the other 85% gradient.58 Higher anxious/depressed values were observed as assessed by CBCL in children suffering the severe form of OSA (55.3 ± 7.9 vs 54.4 ± 7.7), with an ES of 0.12 and variance = 0.02.

The underlying etiological mechanisms for the relationship between depressive symptoms and OSA remains poorly understood, although there are several possible explanations. OSA is associated with blood oxygen desaturation, which may cause micro-awakenings at night, decrease the slow wave stage, and cause restless sleep, thus leading to daytime fatigue and depressive symptoms.59,60 Hypoxia from desaturation might also lead to structural changes in the brain that in turn lead to depressive symptoms.61 In one study, lower blood oxygen desaturation gradients correlated with more profound depressive symptoms among patients with OSA.62 It is also possible that hormonal changes associated with OSA can lead to depressive symptoms. For example, among children with metabolic syndrome, those with OSA were found to exhibit higher leptin levels than those without OSA, suggesting leptin insensitivity in this population (i.e., with leptin insensitivity and relatively lower levels, this leads to increased appetite and weight gain).63 Given that leptin is involved in regulating food intake, leptin insensitivity may lead to obesity. Due to low self-esteem associated with body image and obesity, children and adolescents (especially females) might develop depression.64 Leptin levels normalized after 3 months of continuous positive airway pressure (CPAP).

Alternatively, obesity may contribute to both depressive symptoms and OSA. Obesity is a risk factor for both OSA10 and depression, although the effect of obesity on depression may be greater among adults.65 Obese children are often bullied and can have associated decreased mobility, thus, presenting with higher levels of internalizing symptoms secondary to their appearance (each of which can lead to the other).66,67 More severe OSA was found among obese children than normal-weight children with OSA and those with PS.57,68 Depressive symptoms were also significantly higher in the obese group than the other 2 groups. Likewise, obese patients can have fat deposition around the neck, hypotonia of airway muscles, and limited lung volumes leading to OSA,10 so it is possible that the associations between depressive symptoms and obesity with OSA may be caused by distinct mechanisms.

The effect of depression leading to obesity and worsening OSA has also been reported. Some depressed children have a higher tendency to overeat, have less energy leading to a sedentary lifestyle, and are socially isolated, possibly leading to weight gain and worsening of OSA.69 In addition, OSA has been linked to low serotonin levels, which is associated with depression, to sleep cycle irregularity, a known risk factor for depression, and to upper airway tone dyscontrol, also a risk factor for OSA.61

We found the relation between depressive symptoms and OSA to be greatest in studies with a higher proportion of males. The incidence of both OSA and depression occur equally in preschool children.70 However a higher incidence of depression in females is observed in the post-pubertal period compared to males. OSA, on the other hand, occurs at a higher prevalence and more severe level in males than females after puberty, possibly suggesting a role of anthropometric face bony structure and female hormones as a protective factor to OSA.71 Usually males have coarse bony structures with possibly narrower airway. A dramatic increase in OSA risk occurs in postmenopausal women; this risk was decreased with hormone replacement therapy.71 Of note, some research has found obesity to be more strongly associated with depression in males than females during adolescence.72 This raises the possibility that while the BMI itself did not predict the ES between depressive symptoms and OSA in the current study, obesity and gender may interact such that obese boys with OSA are at greatest risk for increased depressive symptoms. Of note, however, most studies had similar proportions of males and females with the exception of Huang et al., who had a high proportion of males and a high ES. Thus, given that the significant moderator effect of gender on the relation between depressive symptoms and OSA was largely due to this one study, replication of this finding is needed.

Adenotonsillectomy, the main treatment for OSA in children, was associated with decreased depressive symptoms compared to pre-surgery levels. The effect size was fairly consistent across studies, with the exception of a large negative effect size found in one study of only 7 patients.18 Also of note, the ESs appeared to be lower among the 3 that had a comparison group, raising the possibility that some of the observed decrease in depressive symptoms could be related to regression to the mean or due to the effects of administering a measure of depressive symptoms over multiple time points,73 highlighting the need for future studies to include comparison groups of children who did not receive adenotonsillectomy. Although the exact mechanism for this improvement is unclear, improved oxygenation and nighttime sleep might explain children's improvement in depressive symptoms. It is not clear if hormonal normalization (e.g., leptin) might contribute to long-term improvements in children's depressive symptoms. However, weight gain is not an uncommon outcome post-AT surgery in the short term (i.e., within a 6-month period).74 Accordingly, it is possible that such weight gain (usually a change of more than 10%-15% of the baseline weight) would actually contribute to the worsening of OSA and depression in the post-surgery period. It remains unclear whether this weight gain would contribute to the worsening of OSA and relapse and/or worsening of the depressive symptoms later on. Of importance to note, although AT improves the severity of the OSA in most children, it might not cure it in many cases, necessitating reevaluation of possible residual OSA.75 Another treatment option in this population is continuous positive airway pressure (CPAP). Although there are limited studies relating CPAP to depressive symptoms in children, controversies exists in adults. In a study involving 51 patients with OSA treated with CPAP, depressive and anxiety symptoms decreased after 1 and 3 months of treatment.76 However, in a double-blind, placebo control study, CPAP treatment dramatically decreased AHI but had no effect on depressed mood.77 A limitation of these studies included small sample sizes and assessment of depression shortly after treatment duration possibly affecting the outcome.

Finally, OSA in children and in adults has been associated with poor concentration and negative effects on behavior and mood.78,79 A recent meta-analysis80 found a slightly greater relation between sleep disordered breathing and attention deficit hyperactivity disorder symptoms (Hedges' g = 0.57) than was found between OSA and depressive symptoms in the current meta-analysis, indicating that OSA may be related to a variety of psychiatric symptoms. As such, this highlights the importance of screening for emotional and behavioral adjustment among children with OSA.

Several limitations to this study exist. First, several studies included children with PS in the OSA group, possibly lowering the ES for the relationship between depressive symptoms and OSA.1,30,35,36,81 However, when the 4 studies including children with PS were compared to OSA children as measured by depressive symptoms, the ES was almost zero (Hedges' g = 0.04, p = 0.76),29,32,37,57 indicating that the inclusion of children with PS likely did not lower the strength of relationship between OSA and depressive symptoms. This was maintained when incorporating only the 3 studies that used the strict criteria for PS. Second, all of the included studies used either the BASC or CBCL depression scales, which are not necessarily the most comprehensive measures of depressive symptoms in children. The CBCL “anxious/depressed” subscale, for example, includes anxiety as well as depressive symptoms. Moreover, studies of depressive symptoms and OSA have largely relied on parent ratings of depressive symptoms, but self-reports may be more valid for depressive symptom assessment, particularly among adolescents.82 Some depression scales might have better validity than those previously used in this literature. For example, the Center for Epidemiological Studies Depression Scale for Children (CES-DC)83 and the Beck Depression Inventory for adolescents might be preferred.84 On a related note, none of the included studies used a diagnostic interview, which would be the best measure of a diagnosis of depression.85 Inclusion of a diagnostic interview that included the assessment of other psychiatric problems (e.g., anxiety and disruptive behavior disorders) that may be comorbid to depression86 would be helpful to both assess the relation of OSA to clinical depression as well as the extent to which OSA is specific to depression versus other psychiatric problems. A recent meta-analysis, for example, found SDB to have a similar, medium relation to ADHD symptoms as the current meta-analysis found for depressive symptoms.78 Third, the relatively modest number of studies included in the current meta-analysis limits our ability to identify moderators of the relationship between depressive symptoms and OSA. Finally, the definition of OSA varied across studies as some used 1/h as the cutoff, while others used 5/hour. This might suggest that children with milder forms of OSA (AHI between 1-5/h) have the strongest relationship to depressive symptoms. Thus, using a cutoff of AHI of 5/h or more might bias the relationship outcome.

Overall, the current study indicates that there is a medium relationship between depressive symptoms and OSA among children and adolescents. Treatment of depression includes primarily psychotherapy in mild to moderate cases, while psychopharmacological agents (e.g., antidepressant medications) can be used in more severe or therapy unresponsive cases.87 However, medication side effects, especially the debated risk of elevated rates of suicide in child populations, may limit the viability of medication as a treatment option.87 This meta-analysis suggests that depressive symptoms might improve in children having comorbid OSA, without the need for directly treating the depressive symptoms.

This meta-analysis also highlights the importance of screening for depressive symptoms in children presenting with OSA. Yet, well-controlled research is needed. Ideally, children from multiple clinics should be involved, with standardization of diagnostic criteria for OSA and exclusion of those with PS, given that the relationship with PS and depressive symptoms are not well delineated. Close monitoring of the AHI, as well as depressive symptoms before and after AT, and comparison of depressive symptoms in those with cured OSA versus those with residual symptoms will address more accurately whether a decrease in depressive symptoms directly coincides with a decrease in OSA. Despite the need for more research, this meta-analysis suggests that treating OSA may improve children's depressive symptoms, possibly avoiding the need for psychopharmacological treatment.

DISCLOSURE STATEMENT

This was not an industry supported study. The authors have indicated no financial conflicts of interest.

ACKNOWLEDGMENTS

The authors would like to thank Dr. Ron Mitchell and his team for providing supplemental data from their published studies that were included in the meta-analysis.

REFERENCES

1 

Carotenuto M, Esposito M, Parisi L, et al., authors. Depressive symptoms and childhood sleep apnea syndrome. Neuropsychiatr Dis Treat. 2012;8:369–73. [PubMed Central][PubMed]

2 

Glied S, Pine DS, authors. Consequences and correlates of adolescent depression. Arch Pediatrics Adolesc Med. 2002;156:1009–14.

3 

Pine DS, Cohen E, Cohen P, Brook J, authors. Adolescent depressive symptoms as predictors of adult depression: moodiness or mood disorder? Am J Psychiatry. 1999;156:133–5. [PubMed]

4 

Hawkins WE, Hawkins MJ, Seeley J, authors. Stress, health-related behavior and quality of life on depressive symptomatology in a sample of adolescents. Psychol Rep. 1992;71:183–6. [PubMed]

5 

Son SE, Kirchner JT, authors. Depression in children and adolescents. Am Fam Physician. 2000;62:2297–2308. 2311–2. [PubMed]

6 

DiMatteo MR, Lepper HS, Croghan TW, authors. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Int Med. 2000;160:2101–7.

7 

Cardiorespiratory sleep studies in children. Establishment of normative data and polysomnographic predictors of morbidity. American Thoracic Society. Am Respir Crit Care Med. 1999;160:1381–7.

8 

Ali NJ, Pitson DJ, Stradling JR, authors. Snoring, sleep disturbance, and behaviour in 4-5 year olds. Arch Dis Child. 1993;68:360–6. [PubMed Central][PubMed]

9 

Dillon JE, Blunden S, Ruzicka DL, et al., authors. DSM-IV diagnoses and obstructive sleep apnea in children before and 1 year after adenotonsillectomy. J Am Acad Child Adolesc Psych. 2007;46:1425–36.

10 

Sedky K, Akhtar U, Oluwabusi O, authors. The ABCDEs of obstructive sleep apnea. Curr Psychiatry. 2013;12:41–2.

11 

Guilleminault C, Eldridge FL, Tilkian A, Simmons FB, Dement WC, authors. Sleep apnea syndrome due to upper airway obstruction: a review of 25 cases. Arch Int Med. 1977;137:296–300.

12 

Bardwell WA, Berry CC, Ancoli-Israel S, Dimsdale JE, authors. Psychological correlates of sleep apnea. J Psychosom Res. 1999;47:583–96. [PubMed]

13 

Tsapakis EM, Soldani F, Tondo L, Baldessarini RJ, authors. Efficacy of antidepressants in juvenile depression: meta-analysis. Br J Psychiatry. 2008;193:10–7. [PubMed]

14 

Cheung AH, Emslie GJ, Mayes TL, authors. Review of the efficacy and safety of antidepressants in youth depression. J Child Psychol Psychiatry. 2005;46:735–54. [PubMed]

15 

Lipton AJ, Gozal D, authors. Treatment of obstructive sleep apnea in children: do we really know how? Sleep Med Rev. 2003;7:61–80. [PubMed]

16 

Stang A, author. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5. [PubMed]

17 

Chervin RD, Hedger K, Dillon JE, Pituch KJ, authors. Pediatric sleep questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems. Sleep Med. 2000;1:21–32. [PubMed]

18 

Lewin DS, Rosen RC, England SJ, Dahl RE, authors. Preliminary evidence of behavioral and cognitive sequelae of obstructive sleep apnea in children. Sleep Med. 2002;3:5–13. [PubMed]

19 

Chervin RD, Dillon JE, Bassetti C, Ganoczy DA, Pituch KJ, authors. Symptoms of sleep disorders, inattention, and hyperactivity in children. Sleep. 1997;20:1185–92. [PubMed]

20 

Ali NJ, Pitson D, Stradling JR, authors. Sleep disordered breathing: effects of adenotonsillectomy on behaviour and psychological functioning. Eur J Pediatr. 1996;155:56–62. [PubMed]

21 

Ali NJ, Pitson D, Stradling JR, authors. Natural history of snoring and related behaviour problems between the ages of 4 and 7 years. Arch Dis Child. 1994;71:74–6. [PubMed Central][PubMed]

22 

Kohyama J, Furushima W, Hasegawa T, authors. Behavioral problems in children evaluated for sleep disordered breathing. Sleep Hypn. 2003;5:89–94.

23 

Gruber R, Xi T, Frenette S, Robert M, Vannasinh P, Carrier J, authors. Sleep disturbances in prepubertal children with attention deficit hyperactivity disorder: a home polysomnography study. Sleep. 2009;32:343–50. [PubMed Central][PubMed]

24 

Esteller More E, Barcelo Mongil M, Segarra Isern F, et al., authors. Neurocognitive and behavioural abnormalities in paediatric sleep-related breathing disorders. Acta Otorrinolaringol Esp. 2009;60:325–31. [PubMed]

25 

Giordani B, Hodges EK, Guire KE, et al., authors. Neuropsychological and behavioral functioning in children with and without obstructive sleep apnea referred for tonsillectomy. J Int Neuropsychol Soc. 2008;14:571–81. [PubMed Central][PubMed]

26 

Halbower AC, Degaonkar M, Barker PB, et al., authors. Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury. PLoS Med. 2006;3:e301. [PubMed Central][PubMed]

27 

Pagel JF, Snyder S, Dawson D, authors. Obstructive sleep apnea in sleepy pediatric psychiatry clinic patients: polysomnographic and clinical correlates. Sleep Breath. 2004;8:125–31. [PubMed]

28 

Liukkonen K, Virkkula P, Haavisto A, et al., authors. Symptoms at presentation in children with sleep-related disorders. Int J Pediatr Otorhinolaryngol. 2012;76:327–33. [PubMed]

29 

Beebe DW, Ris MD, Kramer ME, Long E, Amin R, authors. The association between sleep disordered breathing, academic grades, and cognitive and behavioral functioning among overweight subjects during middle to late childhood. Sleep. 2010;33:1447–56. [PubMed Central][PubMed]

30 

Blunden S, Lushington K, Kennedy D, Martin J, Dawson D, authors. Behavior and neurocognitive performance in children aged 5-10 years who snore compared to controls. J Clin Exp Neuropsychol. 2000;22:554–68. [PubMed]

31 

Kurnatowski P, Putynski L, Lapienis M, Kowalska B, authors. Physical and emotional disturbances in children with adenotonsillar hypertrophy. J Laryngol Otol. 2008;122:931–5. [PubMed]

32 

Crabtree VM, Varni JW, Gozal D, authors. Health-related quality of life and depressive symptoms in children with suspected sleep-disordered breathing. Sleep. 2004;27:1131–8. [PubMed]

33 

Landau YE, Bar-Yishay O, Greenberg-Dotan S, Goldbart AD, Tarasiuk A, Tal A, authors. Impaired behavioral and neurocognitive function in preschool children with obstructive sleep apnea. Pediatr Pulmonol. 2012;47:180–8. [PubMed]

34 

Huang YS, Guilleminault C, Li HY, Yang CM, Wu YY, Chen NH, authors. Attention-deficit/ hyperactivity disorder with obstructive sleep apnea: a treatment outcome study. Sleep Med. 2007;8:18–30. [PubMed]

35 

O'Brien LM, Mervis CB, Holbrook CR, et al., authors. Neurobehavioral implications of habitual snoring in children. Pediatrics. 2004;114:44–9. [PubMed]

36 

Rosen CL, Storfer-Isser A, Taylor HG, Kirchner HL, Emancipator JL, Redline S, authors. Increased behavioral morbidity in school-aged children with sleep-disordered breathing. Pediatrics. 2004;114:1640–8. [PubMed]

37 

Bourke RS, Anderson V, Yang JS, et al., authors. Neurobehavioral function is impaired in children with all severities of sleep disordered breathing. Sleep Med. 2011;12:222–9. [PubMed]

38 

Ting H, Wong RH, Yang HJ, Lee SP, Lee SD, Wang L, authors. Sleep-disordered breathing, behavior, and academic performance in Taiwan school children. Sleep Breath. 2011;15:91–8. [PubMed]

39 

Sutton AM, author. Executive function in the presence of sleep disordered breathing. 2008. Atlanta, GA: Dissertation, Georgia State University.

40 

Ax EE, author. Implications of sleep disorders symptoms on school behavior , academics, and quality of life. 2006. Tampa, FL: Dissertation, University of South Florida.

41 

Li HY, Huang YS, Chen NH, Fang TJ, Lee LA, authors. Impact of adenotonsillectomy on behavior in children with sleep-disordered breathing. Laryngoscope. 2006;116:1142–7. [PubMed]

42 

Galland BC, Dawes PJ, Tripp EG, Taylor BJ, authors. Changes in behavior and attentional capacity after adenotonsillectomy. Pediatr Res. 2006;59:711–6. [PubMed]

43 

Tran KD, Nguyen CD, Weedon J, Goldstein NA, authors. Child behavior and quality of life in pediatric obstructive sleep apnea. Arch Otolaryngol Head Neck Surg. 2005;131:52–7. [PubMed]

44 

Mitchell RB, Kelly J, authors. Child behavior after adenotonsillectomy for obstructive sleep apnea syndrome. Laryngoscope. 2005;115:2051–5. [PubMed]

45 

Mitchell RB, Kelly J, authors. Long-term changes in behavior after adenotonsillectomy for obstructive sleep apnea syndrome in children. Otolaryngol Head Neck Surg. 2006;134:374–8. [PubMed]

46 

Mitchell RB, Kelly J, authors. Behavioral changes in children with mild sleep-disordered breathing or obstructive sleep apnea after adenotonsillectomy. Laryngoscope. 2007;117:1685–8. [PubMed]

47 

Mitchell RB, Boss EF, authors. Pediatric obstructive sleep apnea in obese and normal-weight children: impact of adenotonsillectomy on quality-of-life and behavior. Dev Neuropsychol. 2009;34:650–61. [PubMed]

48 

Ericsson E, Lundeborg I, Hultcrantz E, authors. Child behavior and quality of life before and after tonsillotomy versus tonsillectomy. Int J Pediat Otorhinolaryngol. 2009;73:1254–62.

49 

Goldstein NA, Fatima M, Campbell TF, Rosenfeld RM, authors. Child behavior and quality of life before and after tonsillectomy and adenoidectomy. Arch Otolaryngol Head Neck Surg. 2002;128:770–5. [PubMed]

50 

Broekman BF, Olff M, Tan FM, Schreuder BJ, Fokkens W, Boer F, authors. The psychological impact of an adenoidectomy and adenotonsillectomy on young children. Int J Pediatr Otorhinolaryngol. 2010;74:37–42. [PubMed]

51 

Walker P, Whitehead B, Gulliver T, authors. Polysomnographic outcome of adenotonsillectomy for obstructive sleep apnea in children under 5 years old. Otolaryngol Head Neck Surg. 2008;139:83–6. [PubMed]

52 

Ye J, Li Y, Liu H, et al., authors. Impact of adenotonsillectomy on quality of life in children with sleep disordered breathing. J Clin Otorhinolaryngol Head Neck Surg. 2007;21:254–8.

53 

Guilleminault C, Huang YS, Glamann C, Li K, Chan A, authors. Adenotonsillectomy and obstructive sleep apnea in children: a prospective survey. Otolaryngol Head Neck Surg. 2007;136:169–75. [PubMed]

54 

Mitchell RB, Kelly J, Call E, Yao N, authors. Long-term changes in quality of life after surgery for pediatric obstructive sleep apnea. Arch Otolaryngol Head Neck Surg. 2004;130:409–12. [PubMed]

55 

Flanary VA, author. Long-term effect of adenotonsillectomy on quality of life in pediatric patients. Laryngoscope. 2003;113:1639–44. [PubMed]

56 

Cohen J, author. Statistical power analysis for the behavioral sciences. 1988. 2nd ed. Lawrence Erlbaum Associates.

57 

Tripuraneni M, Paruthi S, Armbrecht ES, Mitchell RB, authors. Obstructive sleep apnea in children. Laryngoscope. 2013;123:1289–93. [PubMed]

58 

Mulvaney SA, Goodwin JL, Morgan WJ, Rosen GR, Quan SF, Kaemingk KL, authors. Behavior problems associated with sleep disordered breathing in school-aged children--the Tucson children's assessment of sleep apnea study. J Pediatr Psychol. 2006;31:322–30. [PubMed]

59 

Mitchell RB, Kelly J, authors. Behavior, neurocognition and quality-of-life in children with sleep-disordered breathing. Int J Pediatr Otorhinolaryngol. 2006;70:395–406. [PubMed]

60 

Lam RW, author. Sleep disturbances and depression: a challenge for antidepressants. Int Clin Psychopharmacol. 2006;21 Suppl 1:S25–29. [PubMed]

61 

Schroder CM, O'Hara R, authors. Depression and obstructive sleep apnea (OSA). Ann Gen Psychiatry. 2005;4:13. [PubMed Central][PubMed]

62 

Aikens JE, Mendelson WB, authors. A matched comparison of MMPI responses in patients with primary snoring or obstructive sleep apnea. Sleep. 1999;22:355–9. [PubMed]

63 

Nakra N, Bhargava S, Dzuira J, Caprio S, Bazzy-Asaad A, authors. Sleep-disordered breathing in children with metabolic syndrome: the role of leptin and sympathetic nervous system activity and the effect of continuous positive airway pressure. Pediatrics. 2008;122:e634–42. [PubMed]

64 

Reeves GM, Postolache TT, Snitker S, authors. Childhood obesity and depression: connection between these growing problems in growing children. Int J Child Health Hum Dev. 2008;1:103–14. [PubMed Central][PubMed]

65 

Luppino FS, de Wit LM, Bouvy PF, et al., authors. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010;67:220–9. [PubMed]

66 

Roberts AL, Rosario M, Slopen N, Calzo JP, Austin SB, authors. Childhood gender nonconformity, bullying victimization, and depressive symptoms across adolescence and early adulthood: an 11-year longitudinal study. J Am Acad Child Adolesc Psychiatry. 2013;52:143–52. [PubMed]

67 

Pulgaron ER, author. Childhood obesity: a review of increased risk for physical and psychological comorbidities. Clin Ther. 2013;35:A18–32. [PubMed]

68 

Kang KT, Lee PL, Weng WC, Hsu WC, authors. Body weight status and obstructive sleep apnea in children. Int J Obes. 2012;36:920–4.

69 

Rofey DL, Kolko RP, Iosif AM, et al., authors. A longitudinal study of childhood depression and anxiety in relation to weight gain. Child Psych Hum Dev. 2009;40:517–26.

70 

Lumeng JC, Chervin RD, authors. Epidemiology of pediatric obstructive sleep apnea. Proc Am Thorac Soc. 2008;5:242–52. [PubMed Central][PubMed]

71 

Ralls FM, Grigg-Damberger M, authors. Roles of gender, age, race/ethnicity, and residential socioeconomics in obstructive sleep apnea syndromes. Curr Opin Pulm Med. 2012;18:568–73. [PubMed]

72 

Merikangas AK, Mendola P, Pastor PN, Reuben CA, Cleary SD, authors. The association between major depressive disorder and obesity in US adolescents: results from the 2001-2004 National Health and Nutrition Examination Survey. J Behav Med. 2012;35:149–54. [PubMed]

73 

Finch A Jr, Saylor CF, Edwards GL, McIntosh JA, authors. Children's Depression Inventory: Reliability over repeated administrations. J Clin Child Psychol. 1987;16:339–41.

74 

Smith DF, Vikani AR, Benke JR, Boss EF, Ishman SL, authors. Weight gain after adenotonsillectomy is more common in young children. Otolaryngol Head Neck Surg. 2013;148:488–93. [PubMed]

75 

Hsu WC, Kang KT, Weng WC, Lee PL, authors. Impacts of body weight after surgery for obstructive sleep apnea in children. Int J Obes (Lond). 2013;37:527–31.

76 

Sanchez AI, Buela-Casal G, Bermudez MP, Casas-Maldonado F, authors. The effects of continuous positive air pressure treatment on anxiety and depression levels in apnea patients. Psych Clin Neurosci. 2001;55:641–6.

77 

Lee IS, Bardwell W, Ancoli-Israel S, Loredo JS, Dimsdale JE, authors. Effect of three weeks of continuous positive airway pressure treatment on mood in patients with obstructive sleep apnoea: a randomized placebo-controlled study. Sleep Med. 2012;13:161–6. [PubMed Central][PubMed]

78 

Liu X, Zhou H, authors. Sleep duration, insomnia and behavioral problems among Chinese adolescents. Psych Res. 2002;111:75–85.

79 

Roberts RE, Roberts CR, Chen IG, authors. Functioning of adolescents with symptoms of disturbed sleep. J Youth Adolesc. 2001;30:1–18.

80 

Sedky K, Bennett D, Carvalho K, authors. The relationship between attention deficit hyperactivity disorder and sleep disordered breathing in pediatric populations: a meta-analysis. Sleep. 2013;36(Abstract Supplement):A310.

81 

O'Brien LM, Mervis CB, Holbrook CR, et al., authors. Neurobehavioral correlates of sleep-disordered breathing in children. J Sleep Res. 2004;13:165–72. [PubMed]

82 

Moretti MM, Fine S, Haley G, Marriage K, authors. Childhood and adolescent depression: child-report versus parent-report information. J Am Acad Child Psychiatry. 1985;24:298–302. [PubMed]

83 

Faulstich ME, Carey MP, Ruggiero L, Enyart P, Gresham F, authors. Assessment of depression in childhood and adolescence: an evaluation of the Center for Epidemiological Studies Depression Scale for Children (CES-DC). Am J Psychiatry. 1986;143:1024–7. [PubMed]

84 

Bennett DS, Ambrosini PJ, Bianchi M, Barnett D, Metz C, Rabinovich H, authors. Relationship of Beck Depression Inventory factors to depression among adolescents. J Affect Disord. 1997;45:127–34. [PubMed]

85 

Gotlib IH, Lewinsohn PM, Seeley JR, authors. Symptoms versus a diagnosis of depression: differences in psychosocial functioning. J Consult Clin Psychol. 1995;63:90–100. [PubMed]

86 

Maughan B, Collishaw S, Stringaris A, authors. Depression in childhood and adolescence. J Can Acad Child Adolesc Psychiatry. 2013;22:35–40. [PubMed Central][PubMed]

87 

March JS, Silva S, Petrycki S, et al., authors. The Treatment for Adolescents With Depression Study (TADS): long-term effectiveness and safety outcomes. Arch Gen Psychiatry. 2007;64:1132–43. [PubMed]