Abstract
It has been well-established that individuals with ADHD also experience elevated rates of sleep disturbance. However, this relationship is not well-understood, and treatment generally does not differ for individuals with chronic sleep problems, despite the additional challenges that they may face. Numerous theories have been proposed to explain the significant comorbidity between ADHD and sleep problems. These tend to take one of two forms, either (1) contending that the symptoms of one disorder contributes to the manifestation of the other, or else (2) focusing on potential underlying neural pathophysiology common to both concerns. While the direction of effect remains unclear, the considerable literature studying sleep problems in ADHD contains valuable suggestions to improve day-to-day functioning in this population, in addition to providing a critical framework for future research.
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of difficulties sustaining attention, impulsiveness and excessive motor activity. The disorder presents differently among individuals, and can be variably diagnosed as each of three subtypes, with ADHD-Hyperactivity/Impulsivity (ADHD-HI) referring to primarily problems of impulsiveness and excessive motor activity, ADHD-Inattention (ADHD-I) primarily manifesting in attention deficits, and a combination type, ADHD-C characterized by substantial deficits in both domains. In the DSM-5 (2013), the American Psychiatric Association reported that 5% of children have ADHD. Other studies using community samples have estimated that closer to 9% of children and adolescents have ADHD (National Survey of Children’s Health, 2016), making it the most commonly diagnosed mental disorder in children. While ADHD has typically been construed as a disorder of childhood, nearly half of children diagnosed with ADHD will continue to meet the diagnostic criteria as adults.
Literature review
Due to similar or overlapping symptom profiles, ADHD is commonly associated with learning disabilities, conduct disorder and mood disorders, and it is true that children with ADHD are at increased risk of experiencing each of these conditions. However, sleep disorders are actually the most common comorbid disorder in ADHD populations. Indeed, the presence of sleep problems is so common in this population that it was included in the diagnostic criteria for ADHD up until the DSM-IV. Various studies have estimated that between 50% and 75% of children with ADHD also experience a sleep disorder. This comorbidity is even more strongly observed in adult populations, with up to 83% of ADHD adults reporting significant sleep disturbances.
Numerous studies have attempted to elucidate the profile of typical sleep disturbances in ADHD. Studies have identified a wide range of sleep problems in individuals with ADHD, including longer sleep onset latency, disrupted circadian rhythms, non-restorative sleep, poorer sleep efficiency, less total sleep, and daytime sleepiness. Some results have been outright contradictory, especially those measuring sleep architecture; while some polysomnography studies have found significantly shorter duration of REM sleep in ADHD groups compared to controls (Gruber et al., 2008), others have found increased REM sleep (Prehn-Kristensen et al., 2011).
Limitations
There are several factors that may contribute to the conflicting reports populating this area of research. Traditional subjective reports may be biased because of the inability of children to accurately report their own symptoms, and parent proxies may be unaware of sleep problems or downplay their significance compared to the trials of daytime hyperactivity. It also appears that the different ADHD subtypes are associated with different sleep disturbances—perhaps, unsurprisingly, given the considerable differences in symptom presentation among subtypes. Studies of sleep disturbances according to ADHD subtype have found that ADHD-HI is strongly associated with restless sleep (including restless leg syndrome) and parasomnias, while individuals with ADHD-I are more likely to experience excessive daytime sleepiness and hypersomnia, and those with ADHD-C have elevated rates of circadian rhythm disorder (Chiang, Gau, Ni, Chiu, Shang, Wu, Lin, Tai, & Soong, 2010). Although several sleep disturbances have been observed across subtypes, the oversampling of one subtype may bias study results and even produce conflicting results. Treatment of ADHD, which commonly includes stimulant medications, may also be a source of variation among ADHD cohorts. Finally, the presence of other psychiatric comorbidities, like depression, may affect sleep in some individuals with ADHD.
A central problem for researchers and clinicians is the so-called “ADHD-sleep conundrum.” The symptoms and consequences of ADHD and sleep disturbances frequently overlap, and both can cause behavioral problems and impaired academic or professional performance. Deficits in attention, vigilance, memory, emotional regulation, reward-based decision making, and executive function are all common to both ADHD and sleep-disordered populations. As a result, sleep disturbances may mimic, be the consequence of, or contribute to ADHD symptoms. The directionality of the relationship between sleep problems and ADHD is therefore the source of considerable debate.
Linkage Mechanisms
Four principal models have been proposed to explain the relationship between ADHD and sleep disturbances. (1) Elevated rates of sleep problems may follow from the behavioral dysregulation in ADHD, or be the result of the pharmacologic interventions used to treat the disorder. (2) Poor sleep may disrupt neurocognition through its effect on brain plasticity, producing symptoms of ADHD. (3) The relationship may be bidirectional, such that ADHD contributes to poor sleep, and poor sleep contributes to the exacerbation or increased manifestation of ADHD symptoms. (4) Abnormalities in biological systems may underlie both sleep and neurocognitive defects in ADHD.
Effects of ADHD on Sleep
Circadian Rhythm Dysregulation
Several studies have found that non-medicated children with ADHD may have delayed circadian rhythms, as evidenced by a delayed nighttime increase in dim light melatonin (Van der Heijden, Smits, Van Someren, & Gunning, 2005; Van der Heijden, Smits, Van Someren, Ridderinkhof, & Gunning, 2007), as well as observed delays in sleep onset and waking. Adults with ADHD have been shown to have alterations in circadian rhythms at the behavioral, endocrine, and molecular levels (Baird, Coogan, Siddiqui, Donev, & Thome, 2011). It has also been suggested that the circadian-mediated surge in alertness pre-sleep (the so-called “forbidden zone”) is exaggerated in children with ADHD, hindering sleep onset. Increased motor activity observed at the time of sleep onset and resultant increases in sleep latency have often been attributed to the use of psychostimulants in ADHD treatment. However, the disruption of circadian rhythms may be responsible for this effect (Ironside, Davidson, & Corkum, 2010), as well as other sleep abnormalities observed in ADHD populations.
The role of homeostatic dysregulation as a contributor to both the increased propensity for sleep and daytime fatigue in children with ADHD and the oft-reported difficulty with “turning off” mental activity at bedtime (bedtime refusal) has remained largely unexplored. One potential agent of interest is adenosine, a sleep-promoting neuromodulator that accumulates with sleep debt and which is also involved in the effects on dopamine transmission produced by stimulant medications (Mioranzza et al., 2010).
In addition to the internal aspects of the circadian clock, sleep propensity is affected by a variety of physiological, behavioral, and environmental factors to which children with ADHD might be more sensitive. The most prominent such zeitgeber (“time giver”) is light. The effects on internal rhythmicity of evening light exposure may be exacerbated in some children with ADHD, in whom an enhanced sensitivity to evening light delays evening melatonin release. ADHD is also commonly accompanied by sensory-integration deficits, which could increase vulnerability to sleep disturbance due to auditory or tactile stimuli present in the sleep environment. Inattention may manifest at bedtime as increased sensitivity to competing priorities for sleep like watching TV or talking to friends, while the academic difficulties associated with ADHD may preclude sleep if there is still homework to be done. ADHD in adolescence is associated with inconsistent routine, high caffeine intake and overuse of electronic media, all of which might contribute to sleep problems. Children with ADHD also tend to have less routine; the impulsivity and inattention of children with ADHD makes it difficult for caregivers to impose consistent routines (Weiss, Wasdell, Bomben, Rea, & Freeman, 2006). Since the circadian sleep-wake cycle is in part dependent on synchronization of the system by environmental zeitgebers—including light and darkness, but also regular timing of activities like meals or exercise—the variable routines of children with ADHD may serve to “weaken” circadian regulation. In this case, enhancing sleep hygiene and improving sleep behaviors could be an effective strategy to reduce some of the sleep problems associated with ADHD.
Psychostimulant Medication
An intuitive concern is that stimulants used in the treatment of ADHD may lead to sleep disturbances. However, recent subjective and objective studies investigating the effects of stimulants on sleep in ADHD have produced mixed results. Some studies have found that psychostimulant treatment is associated with delayed sleep onset, night awakenings, shorter sleep duration and dyssomnias. Other studies suggest that stimulant medication is associated with reduced sleep-onset latency and more restorative sleep. In adults, results are mixed but generally show positive effects, including reduced sleep onset latency and awakenings and more restorative sleep (Lunsford-Avery, Krystal, & Kollins, ____). In addition, stimulant medications may be associated with an indirect evening “rebound effect,” wherein ADHD symptoms increase over base-line values when the medication wears off. Some sleep problems attributed to stimulant use might therefore be the result of rebound restlessness rather than a direct effect of the medication (Konofal, Lecendreux, & Cortese, 2010); for these individuals, a low evening dose of stimulant medication may actually improve sleep.
Hypoarousal and Sleepiness
A fairly recent addition to the literature argues that ADHD is primarily a disorder of hypoarousal. Based on studies suggesting that children with ADHD have lower baseline levels of arousal—including a higher propensity to fall asleep during the day and greater “daytime sleepiness” (Golan et al., 2004; Lecendreux et al., 2000)—this theory suggests that phenotypical hyperactivity is actually a compensatory strategy to maintain wakefulness and vigilance (Weinberg & Brumback, 1990). If the central biological abnormality associated with ADHD is irregular arousal, it follows that sleep problems are the natural correlate of the disorder. Hypoarousal and irregular sleep propensity may both arise from the dysregulation or impaired coordination of brain centers responsible for maintaining wakefulness, vigilance, and executive control of attention and that promote sleep.
Effects of Sleep on ADHD Symptoms
Sleep Disturbances as a Risk Factor for ADHD
The existence of sleep disturbances like fragmented sleep, bedtime resistance, and sleep onset insomnia in early childhood have been found to be associated with increased likelihood of developing ADHD symptoms later on (Cassoff, Wiebe, & Gruber, ___). Studies have found sleep disturbances at age 4 to be predictive of attention difficulties at age 15. This suggests that sleep disturbances in early childhood maybe either an initial symptom of ADHD, or they may actually be a causal factor in the development of future ADHD symptoms. Furthermore, the stability of impaired sleep over time appears to be an important factor in determining its predictive effect on later ADHD symptoms. These findings suggest that the existence of stable sleep disturbances over childhood may be a significant risk factor for the development of subsequent ADHD.
Effects of Sleep Loss on Cognition, Behavior and Mood
Many of the effects of sleep deprivation are strikingly similar to the core symptoms of ADHD. Sleep loss impairs performance on measures of executive functions, and affects problem-solving, divergent thinking ability and working memory. A substantial literature has demonstrated the link between insufficient sleep or low quality sleep and poorer academic performance (Buckhalt, El-Sheikh, Keller, & Kelly, 2009; El-Sheikh, Buckhal, Cummings, & Keller, 2007; Meijer, 2008; Wolfson, Spaulding, Dandrow, & Baroni, 2007). Sleep loss is also associated with behavioral problems in school, and may contribute to tardiness or truancy (Pagel, Forister, & Kwiatkowki, 2007). If sleep debt becomes sufficiently large, the body may respond by overriding wakefulness, producing excessive daytime sleepiness and moment-to-moment variability in attention and waking cognitive functions requiring executive function. Studies have also shown that insufficient sleep is linked to changes in reward-based decision making, such that adults who have not slept enough take greater risks and are less concerned with potential negative consequences of their behaviors (Dijk, 2011).
Sustained sleep loss also has profound effects on the brain. Animal studies have documented the negative effects of sleep loss on a wide range of basic brain processes (including gene activation and expression, neurogenesis, and protection and repair from injury and stress exposure) that would be expected to impact learning ability and cognitive function (Leibowitz, Lopes, Anderson, & Kushida, 2006). Functional neuroimaging studies have shown that sleep loss produces altered activity in the cerebrum, a region which mediates alertness and attention as well as higher cognitive functions (Diekelmann & Born, 2010; Drummond et al., 2000; Drummond, Gillin, & Brown, 2001; Wu et al., 1991). Sleep deprivation is also linked to vast deactivations in the prefrontal and posterior parietal cortices and the heteromodal association areas, as well as the Brodmann’s areas in the prefrontal and posterior parietal cortices, which are involved in higher-order analysis and integration of sensory-motor information and cognition. In addition, sleep deprivation has effects on brain circuits underlying generation and regulation of emotions, producing heightened emotional response and less emotional control.
This array of effects, many of which mirror precisely the core deficits associated with ADHD, suggest that in some individuals, an underlying sleep disturbance is responsible for the appearance of ADHD symptoms. In others, sustained sleep problems may significantly worsen existing symptoms. Each of these possibilities highlights the importance of addressing chronic sleep problems in patients presenting with both ADHD and sleep difficulties.
Bidirectional Pathways
Sleep Deficits and Clinical Outcomes in ADHD
In addition to the typical effects of sleep loss on neurocognition, specific sleep problems have been linked to greater cognitive impairment in ADHD individuals. Studies have shown that the presence of REM abnormalities is associated with greater deficits in language, attention, visual/spatial cognition, executive function and memory in ADHD samples, while reduced functionality of slow oscillations during REM sleep has been linked to poorer consolidation of declarative memory (Díaz-Román, Hita-Yáñez, & Buela-Casal, ____).
A critical question in modern ADHD research is why some children seem to grow out of the disorder, while for others it persists into adulthood. Sleep disturbance in adolescence is one biological process that may contribute to the persistence of ADHD symptoms. Chronic sleep problems during adolescence may contribute to a vicious cycle for some ADHD youth, in which syndrome-related neural development, cognitive, and psychosocial impairments are compounded by chronic sleep deficits, resulting in greater impairment and maintenance of core ADHD symptoms into adulthood (Lunsford-Avery, Krystal, & Kollins, ____).
– Longitudinal studies of ADHD youth have found evidence for neuro-maturational delays across adolescence: peak cortical thickness/area is delayed by 2-5 years, and there is emerging evidence of a global delay in the development of white matter integrity/connectivity plus slower maturation of specific fiber tracts
– Neurodevelopmental delays in ADHD may contribute to abnormal trajectories of the SWS declines expected to occur during puberty
– SWS abnormalities may in turn interfere with normative neurodevelopment in ADHD
– Studies have shown abnormalities in sleep-dependent areas of the brain (e.g. thalamus) in ADHD youth, as well as parts of the brain commonly impacted by insomnia, including the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC)
Common Underlying Pathophysiology
A final and compelling area of research suggests that a common underlying pathophysiology is responsible for both the symptoms of ADHD and the presence of sleep problems. Despite the high incidence of ADHD, researchers have yet to identify the specific causes of the disorder. That said, some of the structures most strongly implicated in models of ADHD pathophysiology are also closely tied to the regulation of sleep and wakefulness. Various studies have found evidence of abnormalities in the frontal, dorsolateral and ventrolateral prefrontal and dorsal anterior cingulate cortices, as well as in the striatum and lateral temporal and parietal regions in ADHD (Bush, Valera, & Seidman, 2005; Seidman, Valera, & Makris, 2005; Swanson et al., 1998). Dysregulation of limbic-prefrontal circuits and altered connectivity between prefrontal regions and the hippocampus and amygdala, key circuits involved in sleep-dependent learning, have also been observed in ADHD (Konrad & Eickhoff, 2010; Sheridan, Hinshaw, & D’Esposito, 2010; Wang et al., 2009; Zang et al., 2007).
Prefrontal Cortex
A prominent candidate in this research is the prefrontal cortex, which is implicated in the regulation of sleep and wakefulness, as well as executive functioning. Various sleep deprivation studies have found that the functions that are most affected are those controlled by the PFC (namely, the executive functions). These include behavioral inhibition, attentional tasks, set-shifting, working memory, contextual memory, and the analysis and synthesis of information. Deficits in these executive functions is a key symptom of ADHD, and functional neuroimaging studies on people with ADHD have found significant decreases in activity in the prefrontal cortex compared to healthy individuals. Abnormalities in the structure or function of the prefrontal cortex could contribute to both the executive function deficits associated with ADHD, and problems with the regulation of sleep and wakefulness.
Catecholaminergic System
Neuroimaging and genetic studies (Konrad & Eickhoff, 2010; Pagel et al., 2007; Wang et al., 2009; Zang et al., 2007) point to the involvement of the catecholaminergic system in both ADHD and sleep regulation. A number of investigations support the idea that many of the core deficits of ADHD are due to dysregulation of dopamine and norepinephrine. Dopamine especially is strongly associated with ADHD symptomology, as well as the regulation of sleep and waking. Dopamine is important in modulating performance on tasks of executive function, and dopamine levels in the substantia nigra and the ventral tegmental area are involved in promoting wakefulness. Higher dopaminergic activity helps promote wakefulness, while lower dopamine levels are associated with sleep debt. Most medications used in the treatment of ADHD work by increasing the activity of dopamine and norepinephrine in the brain.
Another systems-level variation of interest is COMT, a gene that encodes for a dopamine-degrading enzyme. It has been suggested that COMT activity contributes to sleep problems in individuals with ADHD because of its role in the metabolism of dopamine. The high activity variant of the gene (the Val allele) results in lower concentrations of dopamine compared to the Met allele. Studies comparing sleep in individuals with ADHD with the Val-Val or Val-Met polymorphisms to those with the Met-Met polymorphism found that children with decreased cortical dopamine had worse sleep continuity.
Hypocretin/Orexin System
Studies using MSLT to objectively assess levels of sleepiness/alertness in children with ADHD have found that ADHD patients are objectively “sleepier” than controls (Golan et al., 2004; Lecendreux et al., 2000; Prihodova et al., 2010). One possible explanation involves alterations in the hypocretin/orexin neurotransmitter system in ADHD. This theory suggests that hypocretin/orexin neurons located in perifornical and dorsal medial hypothalamus areas (which increase arousal) are hypoactive, while those located in the lateral hypothalamus (which are associated with reward-processing, appetite, and other reward-seeking behaviors) are hyperactive in children with ADHD (Cortese, Konofal, & Lecendreux, 2008). This theory aligns neatly with the some of the core symptoms of ADHD, and would help explain the existence of comorbid sleep problems in ADHD populations, but more evidence is required.
Gene Alterations
Specific gene alterations, such as those of “clock” genes, may also be common both to ADHD and sleep rhythm disorders. This area still remains largely unexplored, but identified genetic markers have been linked to specific sleep disorders, as well as different circadian preferences. Researchers have raised the possibility that polymorphisms encoding for melatonin-synthesizing enzymes or receptors in “clock” genes in children with ADHD could account for differences in circadian rhythmicity.
Discussion
The relationship between sleep problems and ADHD has been recognized for several decades. Countless researchers have undertaken the task of examining this relationship, but many questions remain unanswered. The prototypical symptoms of ADHD—including irregular levels of arousal, attentiveness, and executive function—intersect in various ways with the domain of sleep, and untangling the relationship between ADHD and disturbed sleep has proven extremely challenging. Several explanations for this comorbidity have been proposed, including (1) that poor sleep is the consequence of disorder-related behavioral symptoms or stimulant use; (2) that the symptoms classified as ADHD, in at least some cases, represent the effects of low quality or dysfunctional sleep that should be treated as the primary concern; and (3) that some underlying neurochemical or structural abnormality is responsible for both the symptoms of ADHD and the presence of sleep disturbances. While there is evidence for each of these theories, some of the most sophisticated research in this field in recent years has pointed to the existence of underlying structural or systemic abnormalities in individuals with ADHD that likely contribute to the elevated rates of sleep disturbance in this population. Future research into the biological causes of ADHD, which remain largely unknown, is imperative, and will likely help explain the nature of the relationship between ADHD and sleep.
Although the precise mechanisms responsible for the elevated rates of sleep disturbance in ADHD populations remain unknown, several preliminary findings—including those linking sleep problems in ADHD individuals to circadian dysregulation, increased sensitivity to external wakefulness cues, and psychostimulant use—can be incorporated into treatment. Improving sleep hygiene practices, monitoring medication intake (especially around bedtime), and maintaining a consistent daily routine are simple interventions that may improve sleep in individuals with ADHD. Attending to the sleep habits of this group is especially important given the possibility that chronic poor sleep may significantly worsen performance in several of the domains where individuals with ADHD already experience deficits. While further research may illuminate the nature of this relationship, it is essential that current treatment programs give due emphasis to importance of quality sleep in order to improve the daily functioning and clinical trajectories of individuals with ADHD.