Sleep in Autism Spectrum Disorder and At
Sleep in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder Kanwaljit Singh, MD, MPH, and Andrew W. Zimmerman, MD
Sleep problems are common in autism spectrum disorder (ASD) and attention deficit
hyperactivity disorder (ADHD). Sleep problems in these disorders may not only worsen
daytime behaviors and core symptoms of ASD and ADHD but also contribute to parental
stress levels. Therefore, the presence of sleep problems in ASD and ADHD requires prompt
attention and management. This article is presented in 2 sections, one each for ASD and
ADHD. First a detailed literature review about the burden and prevalence of different types
of sleep disorders is presented, followed by the pathophysiology and etiology of the sleep
problems and evaluation and management of sleep disorders in ASD and ADHD. Semin Pediatr Neurol ]:]]]-]]] C 2015 Elsevier Inc. All rights reserved.Prevalence and Types of Sleep Disorders in ASD
Sleep Disorders in Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a group of neurodeve- lopmental disabilities characterized by persistent deficits manifesting in early development of social communication and social interaction, restricted and repetitive patterns of behavior interests or activities, and which are not better explained by intellectual disability or global developmental delay. Along with the presence of behavioral issues, ASD is frequently accompanied by a variety of sleep problems that can significantly add on to the disease burden and morbidity in not only the patients themselves but also their families. Sleep problems in children with ASD not only worsen daytime behaviors and core symptoms such as stereotypical and repetitive behavior but also increase parental and family stress levels. Recent Centers for Disease Control and
Prevention reports indicate that the prevalence of ASD has increased dramatically in the past few decades; therefore it is not unreasonable to believe that the burden of sleep disorders has increased proportionally as well. This subsection of the literature review details the burden and types of sleep disorders in patients with ASD as well as the evaluation and treatment of sleep problems in this population.
Although the types of sleep problems that occur in children with ASD generally span the same spectrum of disorders that occur in typically developing children, children with ASD suffer from these problems at a higher rate. The prevalence of sleep disorders in typically developing chil- dren has been estimated to be approximately 25%-40 Children with
ASD also have a higher prevalence of sleep disorders than children with other neurodevelopmental disabilities. Wiggs and reported that as compared with parents of children with developmental disabilities such as Down syndrome and cerebral palsy, parents of children with ASD reported the presence of sleep disorders at a higher rate (68% vs 55% and 43%). Schreck and Mulick, in a study comparing age-matched groups of children with cognitive impairment and developmental disabilities, ASD, and pervasive developmental disorder—not otherwise speci- fied, also reported that parents with children with ASD reported sleep disorders at the highest rate. It is not clear whether there is a relationship between the prevalence of sleep problems in ASD and age. Much of the research evaluating sleep disorders in ASD has been cross-sectional rather than longitudinal, which makes it difficult to accu- rately assess the temporal progression of sleep disorders in ASD. Although on one hand a large retrospective- longitudinal study found no relationship of sleep disorders with developmental stages in ASD, another longitudinal 1071-9091/14/$-see front matter & 2015 Elsevier Inc. All rights reserved.
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From the Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA.
Address reprint requests to Andrew W. Zimmerman, MD, Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Ave N S5-842, Worcester, MA 01655. E-mail: study with a short follow-up of 1 year and a few other cross-sectional studies did find that sleep difficulties tended to decrease with The evidence linking the increased prevalence of sleep problems with severity of cognitive and intellectual disability is also not consistent, with different studies reporting conflicting data. Richdale and found that lower functioning children with ASD (those with intelligence quotient o55) had higher chances of increased sleep latency, shortened total sleep time, and early termi- nation of sleep as compared with higher functioning (intelligence quotient 455) children with ASD. Gail Wil- liams et al reported increased nighttime awakenings in children with ASD along with mental retardation as com- pared with children with ASD but without mental retarda- tion. In contrast, several more studies have found the presence of sleep problems in patients with ASD regardless of their level of cognitive In addition, it has been shown that lack of adequate sleep is associated with increased severity of ASD symptoms such as stereo- typical behaviors, impaired social connectivity, increased aggressiveness, and self-injurious behavior. The types of sleep disorders in ASD can be broadly classified into insomnias, parasomnias, sleep-related breath- ing disorders (SRBDs), and sleep-related movement disor- ders. Sleep-onset insomnia (SOI) or difficulty initiating sleep (increased sleep latency or time to fall asleep) and sleep- maintenance insomnia (decreased sleep duration, decreased sleep continuity, and increased and early awakenings) are among the most common sleep problems reported in ASD.
ASD and 36 typically developing children and found that although nighttime arousals did not differ significantly
Richdale and Prio reported that children with ASD had long sleep latencies, frequent nighttime awakenings, and shortened total sleep time. Couturier et compared 23 pairs of age- and gender-matched ASD and control cases and found that patients with ASD had higher prevalence of sleep onset, sleep duration, and sleep anxiety problems. In ASD, SOI appears to be more common as compared with sleep maintenance insomnia. Gail Williams et al in a survey on 500 children with ASD reported that although difficulty falling asleep, restlessness during sleep, inability to fall asleep in own bed, and frequent nighttime awakenings were common, problems with sleep onset were by far the most frequently reported complaint (53%). Sleepwalking, morn- ing headaches, crying during sleep, and nightmares or night terrors were least comm in a study of 303 ASD and 163 typically developing children also reported that sleep onset problems were more prevalent (as high as 51%) as compared with sleep maintenance problems such as nighttime awakenings (10%) in the ASD group as compared with typically developing children.
Several studies using noninvasive modalities such as actigraphy have confirmed the sleep questionnaire findings that insomnia, specifically sleep-onset insomnia, is the most prevalent in , There are not many studies using polysomnography (PSG) that have been conducted for evaluating sleep disorders in ASD. The few that have been conducted confirm and validate the questionnaire and decreased sleep effi as well as reduced time in bed, total sleep time, sleep period time, and rapid eye movement (REM) Although they are not as common as sleep onset or sleep maintenance insomnias, parasomnias consisting of non-REM
(NREM) and REM sleep-related disorders have been described in ASD. A few studies have reported the occur- rence of NREM arousal conditions such as sleepwalking and night terrors in deeper or slow-wave NREM sleep stages more often than in controls. Patzold et al compared 31
between the 2 groups, the children with ASD, when awakened, stayed awake for a longer period of time and were more likely to experience nightmares (13% vs 11%), nocturnal enuresis (10% vs 3%), and were more likely to indulge in unusual and disruptive behaviors such as muttering to self, grunting, laughing, and head banging. Schreck and Mulick also compared a group of 55 patients with ASD with 49 typically developing children and found that the ASD group experienced more nightmare behaviors such as screaming, sleepwalking, and acting out their dreams. Limoges et al performed PSGs on 16 pairs of adolescent or adult ASD and reference controls and found that patients with ASD had more frequent nocturnal awakenings combined with decreased NREM (stages 2-4) sleep and decreased slow-wave sleep. Ming et al per- formed sleep questionnaires and 2-night PSGs in a group of
23 age-matched ASD and control children pairs, and found that children with ASD had a much higher likelihood of experiencing NREM parasomnias (14 of 23) as compared with the control group children (3 of 23). These findings correlated remarkably well with questionnaire findings, which reported that 16 patients with ASD had NREM parasomnias such as sleep terrors, confusional arousals, sleepwalking, bruxism, and enuresis In an earlier study,
Many parent or caregiver reported studies confirm this
Richdale and did not find an overall increased occurrence of nighttime arousals and nightmares in ASD; rather they reported that typically developing children were more likely to experience these episodes.
A few studies evaluating sleep architecture in ASD have found an increased occurrence of REM-associated sleep disturbances in ASD. Buckley et performed PSG in 60 children with autism, 15 typically developing and 13 with developmental delay, which revealed that children with ASD had a shorter total sleep time, greater slow-wave sleep percentage, and a smaller REM sleep percentage. The study by Limoges et al mentioned earlier also had fewer REMs during the REM sleep stages. The study by Ming et al cited earlier also reported impaired REM architecture whereby the children with ASD experienced increased spontaneous arousals, had prolonged REM latency, and a reduced REM percentage as compared with the control group. Very rarely, REM sleep behavior disorder (RBD) can also occur where the subjects may act on their dreams. Thirumalai et performed nocturnal PSGs on 11 children with ASD who had symptoms of disturbed sleep and nocturnal awaken- however has not been substantiated in subsequent studies, which excluded ASD subjects on psychotropic medications and did not find the occurrence of REM , SRBDs such as obstructive sleep apnea (OSA) may also occur in ASD. The prevalence of SRBDs in the general pediatric population has been estimated to be approximately , described the presence of OSA in 34% of the study sample of 53 children with ASD. The risk factors for SRBD are the same in children with ASD as in typically developing children, for example, obesity, craniofacial abnormalities, abnormalities of muscle tone, the point being that ASD per se does not increase the risk of SRBD. SRBDs in children with ASD may often lead to adverse daytime behavior and possibly worsened core ASD symptoms however, at the same time adverse daytime behaviors are noted in typically developing children with SRBDs too. Indeed, treatment of sleep apnea in a case of ASD was found to improve daytime behaviors (sleep, social communication, inattention, repet- itive behaviors, and hypersensitivity). Similar improve- ments in daytime behavior and inattention have been described in typically developing children after treatment of their Sleep-related movement disorders such as restless legs syndrome (RLS), periodic limb movements in sleep (PLMS), periodic limb movement disorder (PLMD), and rhythmical movement disorder may occur in RLS is a condition characterized by an involuntary urge to move the legs. RLS may occur at any time but is more common at bedtime, is worse during rest, and relieved by movement. PLMS are repetitive stereotypic limb movements during sleep. PLMD is characterized by repetitive stereotypic movements and is accompanied by insomnia and daytime sleepin Rhyth- mic movement disorder is characterized by involuntary, repetitive movements of body parts such as the head, trunk, and limbs that occurs immediately before and during sleep. It most often involves the head and neck and is manifested by head RLS causes SOI, but does not by itself disrupt sleep. PLMD disrupts sleep as the PLMs cause arousals. There are no physical symptoms while awake in PLMD, except that it may cause excessive daytime sleepi- ness. PLMD is diagnosed by PSG. RLS is mainly diagnosed by history. Diagnoses of these conditions such as RLS and PLMS pose special challenges in ASD because of communi- cation and language deficits in children with ASD and because it is very difficult to perform PSG in these children owing to anxiety and sensory Pathophysiology and Causes of Sleep
Disorders in ASD
The causes of sleep disturbances in ASD are many, and they range from genetic mutations and disrupted neurotransmit- ters to medical and psychiatric comorbidities and nutritional deficiencies. Abnormal expressions of several neurotransmit- acid (GABA), have been described in ASD and these neuro- transmitters also play vital roles in maintenance of sleep-wake cycles.
Melatonin and its metabolites are necessary for promoting sleep and some studies have described reduced melatonin levels in found abnormal circadian patterns and reduced serum levels of melatonin in a group of young adults with severe autism. Kulman et al found significantly lower serum melatonin levels in 14 children with ASD as compared with 20 age-matched controls. Tordjman et compared nocturnal urinary excretion of
6-sulphatoxymelatonin (a metabolite of melatonin) in 49
ASD and 88 age-matched controls and found a significantly lower urinary excretion rate of 6-sulphatoxymelatonin in
children with ASD as compared with controls. Genetic mutations in melatonin-regulating pathways have also been described. Melke et al found polymorphisms in genes regulating acetylserotonin-O-methyltransferase (ASMT) and lower levels of ASMT activity in a group of 250 children with ASD as compared with 255 reference controls. Cai et al also found higher rates of partial duplication of the
ASMT gene in a group of 279 subjects with ASD as compared with 248 reference controls. Jonsson et found mutations in regulatory regions of ASMT, melatonin recep- tor 1A, and melatonin receptor 1B in 109 patients with ASD. However, a larger study by Toma et did not find any differences in ASMT gene activity in 390 ASD cases and 490 reference controls.
Melatonin is produced from serotonin, and thus altered serotonin synthesis can lead to abnormal melatonin levels. Some studies have described abnormal platelet serotonin levels in ASD. Connors et measured plasma serotonin levels in 17 children with ASD and their families and discovered lower levels in mothers as well as children with ASD compared with their typical siblings and fathers, in contrast to those in control families. Cook et described reduced serotonin synaptic functional activity in autism. GABA is the primary inhibitory neurotransmitter in the central nervous system and activation of GABA A receptors is necessary for maintenance of sleep-wake Nelson et al have described a disruption of GABA interneurons as manifested by increased peripheral expression of brain- derived neurotrophic factor in 69 children with ASD, as compared with 54 reference controls. A mutation in chromosome 15q that contains GABA genes has also been identifi These mutations may result in disruption of
GABA-related inhibitory functions and thereby contribute to the sleep disorders in ASD.
Several co-occurring medical comorbidities in ASD may also interfere with sleep. Medical conditions such as epilepsy, gastrointestinal disorders (eg, gastric reflux and constipation), and psychiatric comorbidities as well as core behavioral problems in ASD such as depression, anxiety, stereotypic or repetitive and obsessive behavior, environ- mental hypersensitivity, and emotional dysregulation can interfere with sleep continuity and result in a vicious feedback loop whereby these conditions can worsen insom- their typical language and communication deficits can make it difficult for patients with ASD to communicate some of these issues that cause pain and discomfort. Furthermore, medications commonly used to treat seizures (such as lamotrigine and barbiturates) and psychotropic medications (such as methylphenidate, risperidone, and SSRIs) can disrupt sleep. In addition, typical behaviors intrinsic to
ASD (such as sensitivity to environmental stimuli and daytime behavioral problems) may themselves lead to sleep problems.
Potential causes of insomnia in ASD also include nutri- tional deficiencies. These are often a manifestation of personal food preferences related to restricted diet, food phobias, and atypical mealtime rituals and behavio Some studies have reported that as many as 50%-70% of children with ASD may have problems with feeding These behaviors may lead to nutritional deficiencies such as iron deficiency. RLS and PLMD have been shown to be associated with low serum ferritin Studies have demonstrated that correction of iron deficiency in ASD may lead to an improvement of RLS and PLMD.
Evaluation and Management of Sleep Disorders in ASD
The first step in evaluation of sleep disorders in ASD, as in any other condition, is to obtain a thorough medical
psychiatric, sleep, and family history. The sleep history in particular should include detailed information on sleeping habits, such as bedtime, waking time, any pattern of daytime sleepiness, and ability to maintain sleep during the night. It is also important to assess behaviors associated with ASD, especially as nighttime insomnia and daytime sleepiness may manifest as hyperactivity and increased core ASD behaviors. Standardized rating scales to assess behavior, such as the Aberrant Behavior Checklist, and questionnaires such as the Children’s Sleep Habits Questionnaire and Family
Inventory of Sleep Habit may provide vital information on repetitive or stereotypical behavior, aggressiveness, self- injurious behaviors, anxiety, and hyperactivity, as well as providing objective and easily quantified measures of sleep, bedtime routines, and sleep environment. A psychiatric consultation should be obtained if there is a suspicion of a coexisting disorder such as anxiety or depression that may also affect sleep. Family history should be obtained for insomnia or psychopathology such as maternal depression or bipolar disorder, which may help elucidate the child’s sleep problem.
Two investigative modalities are available to evaluate risk factors for primary sleep disorders such as SRBD, RLS or PLMS, or epilepsy: PSG and actigraphy. PSG is a multi- parametric test that involves comprehensive recording of physiological changes occurring during sleep, and monitors brain activity (electroencephalography), eye movements (electrooculography), skeletal muscle activity (electromyog- raphy), and heart rate and rhythm (electrocardiogram). transducers along with respiratory effort using belts. Blood oxygenation is evaluated using pulse oximetry. PSG is clinically useful to identify if there is anything that is disturbing sleep, such as SRBD or OSA and PLMD. PSG in conjunction with multiple sleep latency test (MSLT) can be used to diagnose the presence of hypersomnia and narcolepsy. PSG cannot by itself rule out parasomnias, and in fact is not usually done for establishing or ruling out a parasomnia, as with circadian disorders. It may however be done to find out if another sleep disorder such as SRBD or PLMD is driving a parasomnia. Although PSG is very reliable, its use may be problematic and challenging for children with ASD owing to tactile sensitivity and anxiety in patients with ASD. “Mock” PSG sessions may help in desensitization and improve their tolerance and chances for safe completion of the procedure.
Actigraphy is performed in the home environment, evaluates sleep patterns based on limb movements, and is useful in insomnia. Because of at-home implementation, it is also helpful in cases in which the child has a high degree of anxiety or sensory sensitivities. However, it is important to recognize that PSG and actigraphy cannot be used inter- changeably. That is, actigraphy is not an alternative to a PSG. Indications for each are different. Actigraphy is generally done for several days (2-4 weeks) to get a more objective idea of sleep-wake pattern (than from the history). It is used mainly for Delayed Sleep Phase Syndrome, and, in some instances for insomnia—particularly if a good history is not available or reliable.
Management of Sleep Problems in ASD Treatment of sleep disorders in ASD is multifactorial.
Medical conditions should be evaluated and treated along with sleep disorders. Evaluating for the presence of primary sleep disorders will ensure that the conditions that are treatable (such as OSA) are identified and treated. As described earlier, if a diagnosis of PLMS or RLS is found and subsequent laboratory tests show low ferritin levels, correction of iron deficiency in ASD may lead to an improvement of RLS and PLMS symptoms. If no primary treatable causes are found, the treatment of insomnia is based on a combination of ensuring good sleep hygiene and environment and behavioral interventions. Pharmacologic therapy using melatonin or other drugs such as clonidine should be considered, either in conjunction with behavioral interventions or if the behavioral measures have limited effects.
Sleep Hygiene and Behavioral Interventions
Sleep education and good sleep hygiene along with behav- ioral interventions are the cornerstones of successful man- agement of sleep problems in ASD. Behavioral interventions that involve parents in treating sleep problems in children with ASD are not only helpful in alleviating sleep problems themselves but also improve parental stress levels and their et al conducted a study involving parent-based behavioral interventions and sleep educational workshops on insomnia in parents of 20 children with ASD who had chronic sleep problems. These workshops involved teaching parents about how to establish effective daytime and bedtime routines and habits, and optimize parental interactions during bedtime and nighttime awakenings. At the end of 2 weeks, significant improvements in both subjective (parent-reported Child- ren’s Sleep Habit Questionnaire scores) as well as objective (improved sleep latency) measures of sleep health were assessed the effectiveness of a distance-based approach using telephone contact and pro- viding a treatment handbook for parents of children with
ASD and demonstrated a long-lasting improvement in their children’s sleep onset latency
Good sleep hygiene involves not only bedtime routines but also habits during the daytime and evening routines, and ensuring optimal sleeping environment. Limiting day- time naps and caffeine intake, exercise during the day, and decreasing visual stimulation (especially electronics such as television) during the evening hours all help promote good nighttime sleep habits. Limiting exposure to television and video screens during the evening hours is especially important. Salti et found that daily exposure to tele- vision screens for 1 week in children 6-13 years of age leads to a decrease in urinary excretion of melatonin metabolites. Gooley et al (2011) found that exposure to room light before bedtime suppressed melatonin secretion duration by approximately 90 minutes and a reduction of presleep melatonin levels by 71.4%. Ensuring that the sleeping location is without any unnecessary extraneous lights and distracting noises will help promote good sleep hygiene. Some children may benefit from using a machine that generates “white-noise” which will help buffer distracting noises that interrupt Many children with ASD, on the contrary, may be hypersensitive to background noises; thus ensuring an optimal sleep environment may require some degree of individualization.
In addition to light and sound sensitivity, some children with ASD have tactile sensitivity. It has been suggested that weighted blankets may provide a consistent sensory input, help calm the child, and ensure uninterrupted However, a recent phase 3, randomized, placebo-controlled, crossover trial of weighted blankets in 73 children with ASD failed to demonstrate any significant benefits as measured by actigraphy (such as increased total sleep time or improved behavioral Ensuring a consistent bedtime routine with as little night- to-night variability as possible is very important. Once established, children with ASD respond well to these bed- time routines. These routines should consist of simple bedtime tasks and activities that are performed daily and help with supporting circadian rhythms by serving as time cues. A visual reminder of the bedtime routines is helpful in reinforcing the routines. A “photo-story” consisting of the steps involved in the routines can help and children follow of other children following the bedtime routines may help provide an “example” to follow and help caretakers to communicate the expectation for sleep to the children.
For those children with ASD who are higher functioning and have bedtime resistance (as manifested by crying, calling out, or leaving their rooms at bedtime), positive reinforce- ment behavioral modifications such as the Bedtime Pass Program can be helpful. This program has been shown to be helpful in greatly reducing bedtime resistance—at least in typically developing children, and consists of requiring children to go to bed, providing them with a card exchangeable for 1 trip out of the room or a parental visit. The Autism Treatment Network recommends that this Pass Program may help children with ASD too (ATN/AIR-P Sleep Quick Tips). For those children who have trouble falling asleep (SOI), an approach involving initially moving the bedtime hour to later in the night (the bedtime fading approach) as well as restricting the sleep hours may be helpful. Once the child is trained to fall asleep quickly the time-to-bed may be gradually moved up and sleep hours gradually Another approach that has been considered very helpful
—at least in typically developing children, is a “systematic ignoring” approach which, in its most extreme form (unmodified extinction, or “crying it out” approach) involves putting the child to bed at a designated bedtime and then ignoring the child until a set point the next morning. However, this approach can be understandably distressing to the parents. An alternative “graduated extinc- tion” approach involves gradually weaning the child from the parent being present in the room with the child on a chair until the child falls asleep, and then very gradually moving the chair further out toward the door on successive nights until the child is able to gradually learn to fall asleep alone. The effectiveness of these approaches in children with ASD requires further study.
Pharmacologic Interventions
As described earlier, behavioral intervention and promotion of sleep hygiene are generally the first steps toward treating sleep disorders in ASD. Even though there are no medi- cations approved by the United States Food and Drug Administration specifically for treating insomnia in children, melatonin is frequently used in conjunction with behavioral intervention with variable degrees of success. Synthetic melatonin is available over the counter in both regular (short-acting) and long-acting forms. Several short-term studies have suggested that melatonin is generally efficacious and reasonably well tolerated. Rossignol and Frye con- ducted a metaanalysis combining the data (comprising 57 patients) on 5 randomized, double-blind placebo-controlled trials of melatonin in ASD and found that as compared with placebo, treatment with melatonin (treatment duration of 14 days to 6 months) resulted in an increased sleep duration by 73 minutes and decreased sleep latency by 66 minutes. Andersen et al treated 108 children with ASD using improvements in sleep latency, and these improvements were mostly maintained until the 12-month follow-up visits. The most common side effects, although rare, were parental reports of morning sleepiness and increased enu analyzed 27 studies on the use of melatonin and found no significant overall increase in seizure activity in most studies, and the studies that did report an increase in seizure activity had patients with preexisting uncontrolled seizures.
In clinical practice to treat sleep-onset insomnia, melato- nin is generally prescribed with doses starting at 1 mg approximately 30 minutes before the intended bedtime. Doses may be raised up to as high as 3 mg depending upon clinical efficacy. Very rarely high doses of 6 mg or more may be prescribed. Lower doses of melatonin may be used to advance the timing of sleep onset. In this situation the dose is administered 3-4 hours before bedtime. Long-term administration is needed to maintain the sleep pattern even after the clinical effective dosage has been reached and sleep pattern stabilized. Melatonin has a short half-life of approx- imately 20-50 minutes. Therefore mostly the regular release preparations have been used and are efficacious for sleep- onset insomnia. Its efficacy for sleep maintenance insomnia is less clear. Extended release preparations can be used in these cases but are not available in liquid form.
There is very limited evidence with respect to other medications to treat sleep disorders in ASD. Although Owens et a performed a survey of child and adolescent psychia- trists on the use of drugs such as clonidine, antidepressants, and atypical antipsychotics for treatment of insomnia in their practices, the data on these drugs in ASD are very limited. Ming et performed an open-label study on the use of clonidine in children with ASD and reported its efficacy in reducing sleep latency and nighttime awakenings in the majority of 19 children in the study. The use of other medications such as antidepressants or atypical antipsychotics is usually based on the presence of other coexisting neuro- logic or psychiatric conditions in ASD. For example, risper- idone may be used in patients with ASD who have coexisting aberrant behaviors such as irritability and aggressiveness.
Summary
Sleep disorders are common in ASD and if untreated can significantly add to morbidity. There is no single approach that is helpful in treating these disorders in this population. Management of sleep disorders in ASD is often multifactorial and in most patients may require a degree of individualiza- tion, depending upon their specific needs and symptomatol- ogy. Ultimately, a combination of behavioral interventions and sleep hygiene routines along with pharmacologic agents such as melatonin may be effective. Research into the effective use of drugs is lacking, and more studies, especially placebo- controlled studies, are needed with long-term follow-up to conclusively demonstrate the safety and efficacy of drugs such
Sleep Disorders in Attention Deficit Hyperactivity Disorder
Attention deficit hyperactivity disorder (ADHD) is a chronic condition marked by persistent inattention, varying degrees
of hyperactivity, and sometimes impulsivity. Like autism, many studies have shown a high prevalence of sleep disorders in ADHD. As many as 25%-50% of children and more than 50% of adults with ADHD have been reported to experience sleep problems. Similar to ASD, sleep disturbances in ADHD may affect cognitive and physical function that can worsen ADHD symptoms. However, unlike autism, the evidence in ADHD is rather inconsistent, with a significant discrepancy between the studies using subjective parent questionnaires and studies using objective measures (such as PSG and actigraphy), the latter reporting different types of sleep disorders in ADHD. In addition, there is also a question of whether sleep disorders in ADHD are intrinsic to the disorder or whether they are because of comorbid sleep disorders, or even if in some cases, sleep disorders lead to ADHD-type symptoms. This subsection of the literature review details the burden and types of sleep disorders in patients with ADHD as well as the evaluation and treatment of the sleep problems in this population.
Types of Sleep Disorders in ADHD
Studies Using Parent Questionnaires Several studies using parent questionnaires have consistently reported sleep problems in ADHD, with the most frequent problems reported being SOI, increased nighttime awaken- ings, snoring, parasomnias and nightmares, short total sleep time, and subsequent daytime sleepiness. Ball et al in a comparison of 102 children with ADHD and 78 control children found that parents of children with ADHD more frequently reported the presence of sleep problems (diffi- culty initiating sleep, waking up at night, insisting on keeping a light on during sleep, frequent nightmares, and subsequent daytime fatigue and sleepiness) than the parents of control children. Chervin et al compared 27 children with ADHD and 43 non-ADHD psychiatric controls and found that patients with ADHD reported more habitual snoring than the control group participants. Marcotte et al examined 43 children with ADHD and compared them to 86 reference controls for the presence of sleep and breathing problems, sleepiness, and behavioral problems, using a custom-developed research questionnaire. They found that the ADHD group had worse scores on the sleep and breathing problems scale and sleepiness scale—indicating that children with ADHD were more likely to have severe sleep and breathing Ring et al compared 13 children with ADHD with their 16 healthy siblings and found that children with ADHD had higher rates of SOI and frequent nighttime awakenings, as well as presence of nocturnal enuresis and sleepwalking. Notably, the mean total sleep time did not differ between children with ADHD and controls. Owens et al compared 46 ADHD and had increased rates of SOI, nighttime awakenings, para- somnias, decreased total sleep time, and increased daytime sleepiness.
Stein et administered a sleep questionnaire inquiring about the presence of insomnia, restless sleep, hypersomnia, morning and daytime fatigue, headaches following awaken- ing, snoring, and the use of hypnotics in 17 adolescents with ADHD on medication, 18 adolescents with ADHD not on medication, and 46 reference controls, and found that although nonmedicated participants with ADHD and con- trols did not differ in the presence or severity of sleep disturbances, the medicated participants with ADHD had worse scores on majority of the questionnaire domains, indicating a higher prevalence and increased severity of sleep disturbances. LeBourgeois et al compared the 45 children with ADHD and 29 reference controls for the presence of sleep disturbances, and found that children with ADHD had a higher rate of daytime sleepiness, poor sleep quality, SOI, and trouble waking up in the morning. Shur- Fen Gau investigated the 6-month prevalence rates of sleep-related problems and their association with daytime napping, inattention, hyperactivity, impulsivity, and opposi- tional symptoms in a school-based sample of 2463 children.
They reported that parasomnias, dyssomnias, sleep- disordered breathing problems, daytime inadvertent nap- ping, and abnormal sleep schedules were related to ADHD- related symptoms as assessed by mothers’ and teachers’ Lim et al compared 101 children with ADHD and 60 controls and found a reduced total sleep time in the
ADHD group compared with reference controls. Sung et reported that in a group of 239 children with ADHD, 30% had mild sleep problems and 45% of them had moderate to severe sleep problems such as SOI, nighttime awakenings, restlessness during sleep, and daytime fatigue. Hvolby et in a comparison of 45 participants with ADHD and 276 controls found that children with ADHD had increased bedtime resistance, increased sleep-onset latency, sleep-talking, bruxism, nightmares, and difficulty waking up in the morning as compared with healthy controls. Finally, Li et al, in a large study of 853 participants with ADHD and 19,299 control participants, reported that after control- ling for age, gender, and medication status, a history of ADHD was associated with SOI, sleep anxiety, nighttime awakenings, parasomnias, sleep-disordered breathing, and daytime sleepiness.
Studies Using Objective Modalities In contrast to studies using questionnaires, which more or less consistently reported the presence of similar types of sleep disturbances in ADHD, studies using objective meth- ods such as PSG or actigraphy have reported more variable findings.
Some studies have reported increased sleep-onset latency. Hvolby et performed actigraphy in 45 children with
ADHD, 64 psychiatric controls, and 97 healthy controls, and reported that children with ADHD had significantly longer sleep latencies (26.3 minutes vs o19 minutes in the actigraphy on 87 children with ADHD with SOI and 33 children with ADHD without SOI, and found that the ADHD with SOI group had, not surprisingly, significantly longer sleep onset latency.
Some studies have also reported daytime sleepiness. Palm et al in a small 2-night PSG study of 10 children with deficits in attention, motor control, and perception (DAMP) and 18 reference controls reported that some children with DAMP had decreased sleep onset latency in the MSLT, indicating daytime sleepiness. Golan et al performed
1-night PSG on 34 ADHD and 32 control participants and found that the ADHD group had symptoms suggestive of daytime sleepiness.
Increased REM sleep latency has been described in a few studies. The study by Palm et cited earlier reported an increase in REM sleep latency on the second night of the PSG in patients with DAMP. Busby et performed a 5-night PSG in 11 hyperkinetic children and 11 controls and reported an increased REM latency in the hyperkinetic group. O’Brien et al performed 1-night PSGs in 71 children with ADHD and 39 controls and reported that children with ADHD had an increased REM sleep latency as compared with reference controls. O’Brien et al, in another 1-night PSG study on 100 children with ADHD and 49 reference controls, reported similar findings of increased sleep latency in children with ADHD. Silvestri et al performed 1-night PSGs on 55 children with ADHD and 20 controls and reported that as compared with controls, children with ADHD had an increased REM sleep latency.
There are significant discrepancies among studies as to whether ADHD has an increased or decreased REM sleep percentage. For instance, both of the O’Brien studies mentioned earlier reported a decreased REM sleep percent- age in ADHD as compared with controls. Gruber et al performed 1-night PSG on 15 ADHD and 23 controls and also reported a decrease in REM percentage in the ADHD group. The study by Silvestri et al mentioned earlier also reported that the ADHD group had a decreased REM sleep percentage. The study by Golan et mentioned earlier on the contrary reported an increased REM sleep percent- age. Kirov et performed 2-night PSGs on 17 ADHD and 20 controls and also reported an increased total REM percentage.
Confusion also exists regarding the total sleep time in ADHD as reported in studies using PSG. For example, the study by Kirov et al mentioned earlier reported an increase in total sleep time in ADHD. On the contrary,
Miano et compared 20 pairs of ADHD and control participants in a 2-night PSG study and found a decrease in total sleep time. The study by Gruber et mentioned earlier also reported a decrease in total sleep time in ADHD. Owens et al performed a 5-night actigraphy study on 107 children with ADHD and 46 controls and found that the ADHD group had a decreased real sleep time, which was attributed to more interruptions during sleep. The study by Silvestri et mentioned earlier also reported a decrease There are at least a few studies using actigraphy and PSG that reported no sleep abnormalities in ADHD. Corkum et al performed a 7-night actigraphy on 25 pairs of ADHD and control participants and reported that the actigraphy itself showed no differences between ADHD and controls, although parents reported increased sleep duration, latency, restless sleep, and difficulty getting up in the morning. Wiggs et al had similar findings; they performed a 5-night actigraphy study on 42 ADHD and 21 control participants, and found that, although parents reported some sleep disturbances (earlier sleep onset time and increased latency), there were no significant differences in actigraphies. Crabtree et performed 1-night PSGs on
97 ADHD participants and found that only a small percentage had abnormalities on PSG (6%-7% had sleep- disordered breathing and sleep fragmentation). Sangal et al performed 1-night PSG on 40 ADHD participants and reported no sleep abnormalities. Interestingly though, as both of these studies (Crabtree et al and Sangal et al) did not have a control group, their findings are likely not readily comparable. A few more studies using PSG or actigraphy in ADHD have described night-to-night variability in the sleep architecture. Gruber et performed 5-night actigraphy on 38 children with ADHD and 64 controls, and although they found no significant differences in sleep onset latency or total sleep time between ADHD and controls, the standard deviations of these variables were significantly different between the 2 groups. Gruber and in yet another
5-night actigraphy study on 24 ADHD and 25 control participants, again reported a similar night-to-night varia- bility in sleep onset time, total sleep time, and true sleep time in the ADHD group.
The fact that there is such a wide discrepancy in the types of sleep disturbances reported in the studies using objective methodologies and the way they differed from subjective parent-reported symptoms may be partly due to differences in research methodology. Different investigators used differ- ent methods, for example, actigraphy vs PSG. There also are differences in the duration of follow-up: some studies employed 1-night PSG, others used 2-night PSGs; there are similar differences in the nights that were employed for actigraphy. Some researchers have suggested that the discrepancy between studies using parent reports and those using objective methodologies might be due to parents of children with ADHD being more likely to report a pattern of disturbed sleep in their child, which may not be substan- tiated by objective measures. The diversity of reports may also reveal the complexity of ADHD, where a patient who presents with, for example, ADHD and increased REM sleep, has a type of ADHD that is different from a patient who has
may account for variable outcomes among the studies. Primary Sleep Disorders Causing ADHD-like Symptoms There are at least a few studies which have described
Although it is not known for sure if primary sleep disorders are causative of ADHD or not, sleep fragmentation and sleep deprivation in these disorders may lead to excessive daytime sleepiness, which interferes with attentiveness, mood, mem- ory, and learning processes. compared 74 adults with hypersomnia and 61 adults with ADHD to assess possible diagnostic confusion between excessive day- time sleepiness and ADHD in adults. All patients completed the Epworth Sleepiness Scale. The investigators found that as many as 19% of patients with hypersomnia fulfilled the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria of ADHD.
Some studies have reported the occurrence of ADHD symptoms in RLS and PLMS. Picchietti and Walters conducted a retrospective review of 129 children and adolescents with PLMS, and they found that 93% of children with moderate to severe PLMS had ADHD symp- toms and met the DSM-IV ADHD criteria. Chervin et al, in a large study of 866 children enrolled from community based general pediatrics clinics, found a relatively high correlation between positive hyperactivity index (HI) scores and restless legs as measured by a validated PLMS ques- tionnaire. Gaultney et administered a Pediatric Sleep
Questionnaire to the parents of 283 children and also found a strong correlation between symptoms of PLMS and ADHD. Wagner et evaluated the occurrence of ADHD symptoms in 62 adults with RLS, 32 adults with insomnia, and 77 adult controls, and found that as compared with patients with insomnia and adult controls, a significantly greater percentage of RLS patients with RLS (26% vs 6%) had ADHD symptoms using the age-adjusted DSM-IV ADHD criteria.
Studies have also described an association of ADHD-like symptoms with SRBDs. Chervin and Archbold in an observational study of 113 children with suspected SRBD administered a PSG and Conners Parental Rating Scale and found that children with SRBD on PSG had high hyper- activity scores on the Conners scale. The study by Chervin et mentioned earlier, also found an association between high HI scores and habitual snoring. Urschitz et al explored an association between SRBDs and impaired attention and neurocognitive deficits as assessed by poor school academic performance in 1144 children. They found an association between snoring frequency and intermittent hypoxia (measured by nocturnal home pulse oximetry) and poor school performanc adminis- tered the Connors Abbreviated Symptom Questionnaire on 108 children with suspected SRBD and found a correlation between symptoms of ADHD and SRBD. The study by Gaultney et al described earlier also reported the occur- rence of ADHD symptoms in patients with SRBD. In an earlier study, Ali et al described a significant improve- ment in aggression, inattention, and hyperactivity on the Conners Parental Rating Scale after adeno-tonsillectomy in children with moderate SRBD. A few studies have also described the occurrence of ADHD symptoms in patients with OSA. Lewin et al compared 28 otherwise healthy