Background
Attention-deficit/hyperactivity disorder (ADHD) is a condition characterized by symptoms of inattention or hyperactivity/impulsivity sufficient to cause clinically significant impairment of age-appropriate academic, social, or occupational functioning [
1]. Sleep problems have been frequently reported among children with ADHD [
2,
3]. A recent meta-analysis of subjective and objective studies comparing sleep in children with ADHD versus controls indicated that children with ADHD had significantly higher bedtime resistance, more sleep onset difficulties, night awakenings, difficulties with morning awakenings, sleep-disordered breathing, and daytime sleepiness in subjective studies [
4]. Another meta-analysis of relevant polysomnographic studies revealed that children with ADHD are more likely than controls to suffer from periodic limb movements in sleep [
5]. A recent review reported that sleep problems are very common in children who have ADHD and that the association between ADHD and sleep disturbances has been relatively overlooked in research conducted on ADHD populations [
6]. As recommended by Konofal and colleagues [
7], the relationship between sleep disorders and ADHD should be considered by healthcare practitioners as part of the global approach to the management of ADHD. A previous study reported low serum ferritin levels among children with ADHD [
8]. Similarly, a recent Egyptian study reported low serum ferritin level among Egyptian children with ADHD [
9]. Serum ferritin levels have been associated with the severity of symptoms [
10,
11]. Although several studies have examined the effect of low serum ferritin levels on the severity of symptoms, few studies have examined their effect on the sleep of children with ADHD [
12,
13]. The aim of this study was to describe sleep problems in a sample of Egyptian children with ADHD and to examine the relationship between their sleep, symptom ratings, and low serum ferritin levels. We hypothesized that sleep problems are common among Egyptian children with ADHD, and we expect a significant association between sleep disturbances, symptoms severity, and low serum ferritin levels.
Results
Sample characteristics
Of the total 41 child participants, 35 (85.4%) were boys and 6 (14.6%) were girls. Their ages ranged from 6 to 12 years, with a mean age of 8.03 years (SD = 1.66). The numbers of children with T-scores > 70 (markedly atypical) in oppositional, cognitive problems/inattention, hyperactivity, and ADHD index subscales were 32 (78.0%), 31(75.6%), 33 (80.5%), and 20 (48.8%), respectively. In this sample, 15.0% of fathers were illiterate, 65.0% had a high-school education or less, and 20.0% had graduated from university. Regarding the mothers’ level of education, 12.8% were illiterate, 69.2% had a high-school education or less, and 17.9% had graduated from university. The control group consisted of 62 healthy children, 55 of them were relatives of children with ADHD. The mean age of the control group was 8.60 ± 1.87; 43 (70.5%) were boys. There were no significant differences between the ADHD and control groups with respect to age (t = 1.594, p = 0.114), sex (x
2 = 2.980, p = 0.084), fathers’ level of education (x
2 = 1.680, p = 0.314), or mothers’ level of education (x
2 = 2.579, p = 0.303).
Sleep/wake patterns
The mean (±SD) night bedtime of the ADHD group was 23.15 ± 1.34, the mean morning wake-up time was 8.11 ± 1.42, and the mean total sleep duration was 9.40 ± 1.66 h. The mean (±SD) night bedtime of the control group was 23.24 ± 1.52, the mean morning wake-up time was 7.77 ± 2.23, and the mean total sleep duration was 9.42 ± 1.38 h. There was a significant difference between the ADHD and control groups with respect to bed time (t = 2.220, p = 0.029). There were no significant differences in wake-up time (t = 0.891, p = 0.376) or total sleep duration (t = 0.062, p = 0.951).
Comparisons of CSHQ scale scores
Comparisons of CSHQ scale scores for the ADHD and control groups are shown in Table
1. There were significant differences in bedtime resistance, sleep anxiety, parasomnias, sleep-disordered breathing, daytime sleepiness, and total scale score (p < 0.05). There was marginal difference between groups in sleep duration subscale (p = 0.056). There were no significant differences with respect to sleep-onset delay or night wakings subscales (p > 0.05).
Table 1
Comparison of CSHQ scale scores between ADHD and control groups
CSHQ subscales | | | | |
Bedtime resistance | 11.9 ± 3.0(41) | 9.4 ± 2.2(62) | 4.906 | <0.001 |
Sleep-onset delay* | 1.8 ± 0.7(40) | 1.7 ± 0.8(61) | 0.294 | 0.769 |
Sleep duration* | 5.2 ± 1.7(41) | 4.6 ± 1.7(61) | 1.933 | 0.056 |
Sleep anxiety | 8.0 ± 2.4(41) | 6.1 ± 2.0(62) | 4.413 | <0.001 |
Night wakings* | 5.1 ± 1.9(40) | 5.1 ± 1.5(62) | 0.085 | 0.932 |
Parasomnias | 11.9 ± 2.9(41) | 9.6 ± 3.3(62) | 3.567 | 0.001 |
Sleep-disordered breathing* | 4.6 ± 1.9(40) | 3.9 ± 1.5(62) | 2.021 | 0.046 |
Daytime sleepiness | 15.9 ± 3.5(41) | 14.2 ± 3.3(62) | 2.402 | 0.018 |
Total score | 60.0 ± 10.4(41) | 51.5 ± 9.2(62) | 4.400 | <0.001 |
The effect of ferritin levels on CSHQ scale scores
As shown in Table
2, there were no significant differences in CSHQ subscale scores or the total score with respect to ferritin levels (p > 0.05). There was a marginal difference between groups with respect to the total score (p = 0.05).
Table 2
The Children’s Sleep Habits Questionnaire scale scores according to ferritin levels
CSHQ subscales | | | | |
Bedtime resistance | 12.3 ± 2.9(25) | 11.3 ± 3.0(16) | 1.093 | 0.281 |
Sleep-onset delay* | 1.9 ± 0.7(24) | 1.6 ± 0.7(16) | 1.316 | 0.196 |
Sleep duration | 5.6 ± 1.7(25) | 4.7 ± 1.5(16) | 1.750 | 0.088 |
Sleep anxiety | 8.4 ± 1.9(25) | 7.4 ± 3.0(16) | 1.133 | 0.269 |
Night wakings* | 5.5 ± 1.5(24) | 4.6 ± 2.3(16) | 1.398 | 0.170 |
Parasomnias | 12.1 ± 3.1(25) | 11.6 ± 2.5(16) | 0.556 | 0.581 |
Sleep-disordered breathing* | 5.0 ± 2.2(25) | 4.1 ± 1.2(15) | 1.703 | 0.097 |
Daytime sleepiness | 16.7 ± 2.5(25) | 14.6 ± 4.5(16) | 1.714 | 0.101 |
Total score | 62.5 ± 8.5(25) | 56.1 ± 12.0(16) | 2.00 | 0.052 |
Correlation between serum ferritin levels and CSHQ scale scores
As shown in Table
3, there were significant negative correlations between serum ferritin levels and sleep duration subscale (
r = -0.309, p = 0.049) and total score (
r = -0.363, p = 0.020).
Table 3
Correlation between serum ferritin levels and CSHQ scale scores
CSHQ subscales | | |
Bedtime resistance | -0.240 | 0.131 |
Sleep-onset delay | -0.239 | 0.137 |
Sleep duration | -0.309 | 0.049 |
Sleep anxiety | -0.284 | 0.072 |
Night wakings | -0.289 | 0.070 |
Parasomnias | -0.139 | 0.388 |
Sleep-disordered breathing | -0.195 | 0.227 |
Daytime sleepiness | -0.286 | 0.070 |
Total score | -0.363 | 0.020 |
The effect of ferritin levels on CPRS-R:L subscale scores
As shown in Table
4, there were no significant differences in hyperactivity, cognitive problems/inattention, oppositional, or ADHD index subscale scores between children with serum ferritin levels <30 ng/mL and those with serum ferritin levels ≥30 ng/mL (p > 0.05).
Table 4
Conners’ Parent Rating Scale-Revised: Long Version (CPRS-R:L) subscales according to ferritin levels
CPRS-R:L subscales | | | | |
Oppositional | 21.2 ± 4.0 | 18.4 ± 5.9 | 1.761 | 0.086 |
Cognitive Problems/Inattention | 26.6 ± 6.7 | 26.4 ± 5.5 | 0.132 | 0.896 |
Hyperactivity | 18.6 ± 4.8 | 16.4 ± 4.4 | 1.530 | 0.134 |
ADHD index | 26.7 ± 5.5 | 24.7 ± 4.3 | 1.250 | 0.219 |
Correlation between serum ferritin levels and CPRS-R:L subscale scores
Table
5 shows that there were no significant correlations between serum ferritin levels and hyperactivity, cognitive problems/inattention, oppositional, or ADHD index subscale scores (p > 0.05).
Table 5
Correlation between serum ferritin levels and Conners’ Parent Rating Scale-Revised: Long Version (CPRS-R:L) subscale raw scores
CPRS-R:L subscales | | |
Oppositional | -0.277 | 0.080 |
Cognitive Problems/Inattention | -0.044 | 0.784 |
Hyperactivity | -0.094 | 0.559 |
ADHD index | -0.003 | 0.984 |
Discussion
We conducted this study to describe sleep problems in a sample of Egyptian children with ADHD and to investigate the relationship between their sleep, symptom-ratings, and low serum ferritin levels. The results show that the ADHD group had significantly higher scores in bedtime resistance, sleep anxiety, parasomnias, sleep-disordered breathing, daytime sleepiness, and global sleep disturbance (CSHQ total score) than the control group. Our results are in agreement with those of previous studies that have reported a high prevalence of sleep disturbances in children with ADHD. Owens et al. [
17] found that children with ADHD had significantly higher scores on all sleep subscales of the CSHQ than did controls. A recent study of 27 children with ADHD and 26 healthy controls reported that the ADHD group had significantly higher scores with respect to sleep-onset delay, sleep duration, night waking, parasomnias, daytime sleepiness, and total sleep disturbance factors [
18]. As reviewed by Owens [
19], several recent reports have documented a significant increase in parent-reported sleep-disordered breathing symptoms specifically in children being evaluated for or diagnosed with ADHD. Golan and colleagues [
20] reported that 50% of children that were diagnosed with ADHD had signs of sleep-disordered breathing, compared with 22% of children in the control group. In agreement with these studies, our study revealed higher sleep-disordered breathing subscale scores in children with ADHD. Several studies using the multiple sleep latency test have revealed that children with ADHD exhibit significantly more daytime sleepiness than controls [
20,
21]. A recent systematic review suggested that children with ADHD exhibit a greater extent of daytime sleepiness than controls [
22]. Recently, an association between obesity and ADHD has been reported [
23], and excessive daytime sleepiness has been implicated in this association [
24]. The present study showed that children with ADHD had higher daytime sleepiness subscale scores than did controls. Gruber and colleagues [
25] reported an ADHD group with higher scores regarding insufficient sleep and sleep anxiety factors, and they suggested that sleep-onset problems and daytime sleepiness in children with ADHD resemble the clinical picture of circadian phase delay and that the sleep problems that characterized children with ADHD might be related to the circadian system. Van der Heijden and colleagues [
26] reported that children with ADHD and chronic idiopathic sleep-onset insomnia showed a delayed sleep phase and delayed dim-light melatonin onset compared with ADHD children without sleep-onset insomnia. This proposed circadian rhythm model could explain the high rate of bedtime resistance and daytime sleepiness among our sample.
Another important finding of this study is the association between serum ferritin levels and sleep disturbances. Previous studies have demonstrated a significant relation between serum ferritin levels and sleep disturbances in children with ADHD. Konofal et al. [
27] reported improvement in sleep problems, assessed by parental interview and sleep diaries filled out by the parents, in a child with ADHD after iron supplementation for low ferritin levels. Another study reported improvement in total score, hyperactive/impulsive, and inattentive subscales of the ADHD Rating Scale and restless leg symptoms after iron supplementation [
28]. In a recent study of 68 children with ADHD, aged 6 to 14 years, Cortese and colleagues [
13] found that children with serum ferritin levels <45 μg/L had significantly higher scores on the sleep-wake transition disorders (SWTD) subscale of the Sleep Disturbance Scale for Children (SDSC) compared with children with serum ferritin levels ≥ 45 μg/L, and there was a significant inverse correlation between the serum ferritin levels and SWTD scores. The authors concluded that serum ferritin levels <45 μg/L might indicate a risk for sleep-wake transition disorders, including abnormal sleep movements, in children with ADHD. In agreement with these studies, our study revealed a significant negative correlation between serum ferritin levels and global sleep disturbance score (CSHQ total score). In addition, children with low serum ferritin had higher scores on CSHQ scales. However, this difference did not reach statistical significance, which could be attributed to the small sample size of this study. A future study featuring a larger sample size might reveal significant differences.
The mechanism through which low serum ferritin levels could affect the sleep of children with ADHD has not been previously studied. A recent study of brain iron levels in children with and without ADHD using magnetic resonance imaging reported that children with ADHD showed significantly lower estimated brain iron levels in the right and left thalamus compared to healthy controls and suggested that low iron in the thalamus may contribute to ADHD pathophysiology [
29]. Konofal and colleagues [
28] suggested that brain iron stores influence the monoamine-dependent functions in ADHD. The catecholamine systems have been implicated in the regulation of sleep and arousal [
6]. It was proposed that a potential dysfunction of dopaminergic pathways may play a significant role in the association between iron deficiency and increased motor activity in the sleep of children with ADHD [
13].
A number of studies have demonstrated a significant association between serum ferritin levels and severity of symptoms in children with ADHD [
10,
11]. A recent Indian study [
30] revealed a significant negative correlation between serum ferritin levels and oppositional sub-score on Conners’ Rating Scale. Oner and colleagues [
10] reported that lower ferritin levels were associated with higher hyperactivity scores in parental ratings. In contrast to previous studies, Millichap et al. [
31] found no significant difference in severity of attention-deficit hyperactivity disorder symptoms in 12 children with serum ferritin levels <20 ng/mL compared with 12 children with levels >60 ng/mL. Another recent study assessed the serum ferritin levels in 101 children with ADHD and 93 controls and examined the association between serum ferritin levels and ADHD severity, reporting that serum ferritin levels did not significantly differ between children with ADHD and controls and correlations between serum ferritin levels and measures related to ADHD severity were not significant [
32]. Similarly, we did not find significant correlations between serum ferritin levels and symptoms severity. Moreover, there were no significant differences in hyperactivity, cognitive problems/inattention, oppositional, or ADHD index subscales with respect to serum ferritin levels.
The main limitation of this study is that children’s sleep and symptom ratings were assessed by reports from parents, who were the only informants, which may lead to over-or underestimation of sleep and symptom severity. Another limitation is that children were recruited from a psychiatric clinic that may attract severe cases of ADHD; thus, the results may not be generalized to community children with ADHD. The sample size of this study was small and further research with a larger sample size is recommended. An objective study using polysomnography would be more effective in examining sleep disturbances among children with ADHD rather than parental reports, and further research is required to investigate the impact of low serum ferritin levels on children’s sleep and to understand the possible mechanisms underlying their behavior.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
MKA and ORA contributed to the conception and design of this study. OGS performed the laboratory analysis, and TMR performed the statistical analysis. All authors read and approved the final manuscript.