**2. ADHD and sleep**

Sleep disturbance is by far one of the most reported problems (>80%) especially by parents and care-takers, who commonly recount restless, inadequate and often delayed and/or fragmented sleep in their children.

A clear distinction, however, needs to be drawn between subjective and objective sleep reports and, with respect to the latter, actigraphyc versus video-polysomnographic (vPSG) studies present a palpable difference in terms of method and quality of data accessed.

Several metanalytic reviews have been published within the last ten years, dealing with many confounding factors including gender, referral source, age range, co-morbid disorders, first versus follow-up visits, medications, number of studied nights with or without adaptation. (Owens, 2005; Cortese et al., 2006; Sadeh et al., 2006).

They all address, through various approaches, the multilevel/dimensional relationship among sleep alterations and neurobehavioral/neurocognitive functioning.

Sleep Disorders Diagnosis and Management in

influence sleep attitude and propensity.

hyperactivity is concerned.

increased number of sleep cycles.

children with periodic limb movements.

**3.1 Microstructural aspects of sleep** 

according to most estimates, and children with sleep disorders.

and neurotransmitter systems, which may deeply influence sleep patterns.

of first night sleep deprivation and adaptation to the lab conditions.

REM effect were more consistent with the IADHD type.

Children with Attention Deficit/Hyperactivity Disorder (ADHD) 33

confounding factors such as the effect of medications, co-morbid neurological and psychiatric conditions and, above all, primary sleep disorders. In fact, ADHD children could be generally subdivided in children without sleep disorders, probably less than 50%

Many authors claim that in the absence of an abnormal apnea hypopnea index (AHI) or periodic leg movements (PLMs) index, sleep variables in ADHD children are not far from age normative values (Sangal et al., 2005). In a recent thorough metanalysis of polysomnographic (PSG) studies, Sadeh et al. (2006) examined other factors of variance, including age and gender. Age, in fact, reflects maturational changes of neurobehavioral

Females with ADHD usually present less disruptive behaviors, which can also differentially

Whether or not an adaptation night is performed, it may enable the exclusion of the effects

All considered, total sleep time appears to be longer in comparison to controls in ADHD children who underwent an adaptation night. The same subjects also exhibited longer stage 2 than controls (Sadeh et al., 2006); there appears to be a gender-related effect also over time spent in stage 2, but the most consistent effect of TST and stage 1 time was age-related, with a shorter TST and longer stage 1 in younger children (<9 years) compared to older children (>9 years), as if to indicate a more severe sleep impact in the younger group, which is usually also more severely affected in terms of ADHD symptoms, especially as far as

A critical review (Bullock & Schall, 2004) examining dyssomnia in ADHD children, reports an overall concordance between authors (O'Brien et al., 2003a; Miano et al., 2006; Silvestri et al., 2009) with respect to a decreased REM percentage and an increased REM latency in ADHD kids. Most reports from France, however, contradict these studies (Lecendreux et al., 2000, Konofal et al., 2001). Furthermore, these data are not confirmed in most studies on HADHD children with nighttime periodic limb movements (Crabtree et al., 2003), as if the

Kirov et al. (2004), instead, noticed an increased duration of REM sleep and of the number of sleep cycles in ADHD children compared to controls. Also, REM latency resulted shorter in his subjects as already previously reported by Kahn (1982) and Greenhill (1983), as if a forced REM initiation may have produced a longer REM sleep duration along with an

A decreased dopaminergic activity in ADHD may be responsible for cortical dysinhibition of the motor frontal cortices, which would in turn result in the forced ultradian cycle of ADHD with REM-increased propensity. Later on, the same group reported an increased REM drive with shorter REM latency in children with coexisting tick disorders and ADHD, ascribing this type of impact to hypermotor symptoms (Kirov et al., 2007), partially contradicting previous findings (Crabtree et al., 2003) on reduced REM sleep in ADHD

What almost all authors agree about is an increase of sleep oscillations within the night that contribute to the overall daytime "hypoarousal" phenotype via a possible decrease of sleep efficiency (Gruber et al., 2007). However, while a few authors notice an increase of

In particular, the interaction of sleep with attention/arousal mechanisms in children has been highlighted by most recent studies.

#### **2.1 Subjective reports**

Items more often referred to by subjective studies on sleep and alertness in ADHD include (Cortese et al., 2006): bedtime resistance, sleep onset insomnia, night awakening, sleep duration, restless sleep, parasomnias, problems with morning awakening, sleep disordered breathing (SDB) excessive daytime sleepiness (EDS).

No major differences between adolescents with ADHD and controls were detected (Mick et al., 2000) after excluding confounding factors such as medications and psychiatric comorbidity. As for ADHD children, significantly over reported by comparison with controls were EDS (Marcotte et al., 1998, Owens et al., 2000), whether or not sleep disordered breathing (SDB) related, movements during sleep (Corkum et al., 1999, Owens et al., 2000). Also a longer sleep duration with increased night awakenings and parasomnias were observed upon comparison with controls (Owens et al., 2000). Despite the fact that bedtime resistance and sleep onset insomnia did not come across as significantly different by comparison with control subjects, after controlling for psychiatric co-morbidity and medications, it cannot be ruled out that a subgroup of ADHD children may display significant difficulties with sleep onset. Endogenous circadian alterations have been postulated by several authors (Vander Heijden et al., 2005) along with forced ultradian cycling (Kirov et al., 2004), which would make these children more prone to a delayed sleep phase (DSP). In this respect, melatonin use before bedtime with different regimen schedules and dosing has been acknowledged by several clinicians (Hodgkins et al., 2011; Owens et al., 2010; Larzelere et al., 2010).

#### **2.2 Objective studies**

Only a few actigraphic studies (Wiggs et al., 2005; Dagan et al., 1997; Corkum et al., 2001) and few video PSG studies were obtained in ADHD children, probably due to objective constraints as imposed by health policies, children restless and oppositional behavior and parents' reticence to over-night hospitalization. Concerning actigraphic studies, measures of objective sleep patterns (sleep duration, activity mean, wake time and number of awakenings) resulted not predictive of ADHD symptom severity after regression analysis (Wiggs et al., 2005) and did not correspond to parents' reports except for waking time in the morning. In particular, bedtime for the IADHD children was usually grossly underestimated by their parents, probably because of less externalizing behaviors during daytime.

Correspondence between subjective and objective assessment has been usually inconsistent with a few exceptions (Acebo et al., 1999). In fact, despite an overall very high parental report of sleep disturbance, actigraphic data did not confirm parents' concerns. Of course, some of these results could rely on the inherent incapacity of actigraphy to confirm specific sleep disorders such as SDB or sleep fragmentation at a microstructural level. Nevertheless, these results may still prove of some utility in order to provide parental reassurance and correct some of their distorted beliefs.

#### **3. Sleep architecture**

Sleep architecture with phase distribution, wake time, arousal and sleep fragmentation could be seen at best only via PSG studies. A major issue in this context is the exclusion of

In particular, the interaction of sleep with attention/arousal mechanisms in children has

Items more often referred to by subjective studies on sleep and alertness in ADHD include (Cortese et al., 2006): bedtime resistance, sleep onset insomnia, night awakening, sleep duration, restless sleep, parasomnias, problems with morning awakening, sleep disordered

No major differences between adolescents with ADHD and controls were detected (Mick et al., 2000) after excluding confounding factors such as medications and psychiatric comorbidity. As for ADHD children, significantly over reported by comparison with controls were EDS (Marcotte et al., 1998, Owens et al., 2000), whether or not sleep disordered breathing (SDB) related, movements during sleep (Corkum et al., 1999, Owens et al., 2000). Also a longer sleep duration with increased night awakenings and parasomnias were observed upon comparison with controls (Owens et al., 2000). Despite the fact that bedtime resistance and sleep onset insomnia did not come across as significantly different by comparison with control subjects, after controlling for psychiatric co-morbidity and medications, it cannot be ruled out that a subgroup of ADHD children may display significant difficulties with sleep onset. Endogenous circadian alterations have been postulated by several authors (Vander Heijden et al., 2005) along with forced ultradian cycling (Kirov et al., 2004), which would make these children more prone to a delayed sleep phase (DSP). In this respect, melatonin use before bedtime with different regimen schedules and dosing has been acknowledged by several clinicians (Hodgkins et al., 2011; Owens et

Only a few actigraphic studies (Wiggs et al., 2005; Dagan et al., 1997; Corkum et al., 2001) and few video PSG studies were obtained in ADHD children, probably due to objective constraints as imposed by health policies, children restless and oppositional behavior and parents' reticence to over-night hospitalization. Concerning actigraphic studies, measures of objective sleep patterns (sleep duration, activity mean, wake time and number of awakenings) resulted not predictive of ADHD symptom severity after regression analysis (Wiggs et al., 2005) and did not correspond to parents' reports except for waking time in the morning. In particular, bedtime for the IADHD children was usually grossly underestimated by their parents,

Correspondence between subjective and objective assessment has been usually inconsistent with a few exceptions (Acebo et al., 1999). In fact, despite an overall very high parental report of sleep disturbance, actigraphic data did not confirm parents' concerns. Of course, some of these results could rely on the inherent incapacity of actigraphy to confirm specific sleep disorders such as SDB or sleep fragmentation at a microstructural level. Nevertheless, these results may still prove of some utility in order to provide parental reassurance and

Sleep architecture with phase distribution, wake time, arousal and sleep fragmentation could be seen at best only via PSG studies. A major issue in this context is the exclusion of

probably because of less externalizing behaviors during daytime.

been highlighted by most recent studies.

breathing (SDB) excessive daytime sleepiness (EDS).

**2.1 Subjective reports** 

al., 2010; Larzelere et al., 2010).

correct some of their distorted beliefs.

**3. Sleep architecture** 

**2.2 Objective studies** 

confounding factors such as the effect of medications, co-morbid neurological and psychiatric conditions and, above all, primary sleep disorders. In fact, ADHD children could be generally subdivided in children without sleep disorders, probably less than 50% according to most estimates, and children with sleep disorders.

Many authors claim that in the absence of an abnormal apnea hypopnea index (AHI) or periodic leg movements (PLMs) index, sleep variables in ADHD children are not far from age normative values (Sangal et al., 2005). In a recent thorough metanalysis of polysomnographic (PSG) studies, Sadeh et al. (2006) examined other factors of variance, including age and gender. Age, in fact, reflects maturational changes of neurobehavioral and neurotransmitter systems, which may deeply influence sleep patterns.

Females with ADHD usually present less disruptive behaviors, which can also differentially influence sleep attitude and propensity.

Whether or not an adaptation night is performed, it may enable the exclusion of the effects of first night sleep deprivation and adaptation to the lab conditions.

All considered, total sleep time appears to be longer in comparison to controls in ADHD children who underwent an adaptation night. The same subjects also exhibited longer stage 2 than controls (Sadeh et al., 2006); there appears to be a gender-related effect also over time spent in stage 2, but the most consistent effect of TST and stage 1 time was age-related, with a shorter TST and longer stage 1 in younger children (<9 years) compared to older children (>9 years), as if to indicate a more severe sleep impact in the younger group, which is usually also more severely affected in terms of ADHD symptoms, especially as far as hyperactivity is concerned.

A critical review (Bullock & Schall, 2004) examining dyssomnia in ADHD children, reports an overall concordance between authors (O'Brien et al., 2003a; Miano et al., 2006; Silvestri et al., 2009) with respect to a decreased REM percentage and an increased REM latency in ADHD kids. Most reports from France, however, contradict these studies (Lecendreux et al., 2000, Konofal et al., 2001). Furthermore, these data are not confirmed in most studies on HADHD children with nighttime periodic limb movements (Crabtree et al., 2003), as if the REM effect were more consistent with the IADHD type.

Kirov et al. (2004), instead, noticed an increased duration of REM sleep and of the number of sleep cycles in ADHD children compared to controls. Also, REM latency resulted shorter in his subjects as already previously reported by Kahn (1982) and Greenhill (1983), as if a forced REM initiation may have produced a longer REM sleep duration along with an increased number of sleep cycles.

A decreased dopaminergic activity in ADHD may be responsible for cortical dysinhibition of the motor frontal cortices, which would in turn result in the forced ultradian cycle of ADHD with REM-increased propensity. Later on, the same group reported an increased REM drive with shorter REM latency in children with coexisting tick disorders and ADHD, ascribing this type of impact to hypermotor symptoms (Kirov et al., 2007), partially contradicting previous findings (Crabtree et al., 2003) on reduced REM sleep in ADHD children with periodic limb movements.

#### **3.1 Microstructural aspects of sleep**

What almost all authors agree about is an increase of sleep oscillations within the night that contribute to the overall daytime "hypoarousal" phenotype via a possible decrease of sleep efficiency (Gruber et al., 2007). However, while a few authors notice an increase of

Sleep Disorders Diagnosis and Management in

trial of bright-light therapy in the morning.

on performance (Gruber et al., 2007).

ADHD adults (Oosterloo et al., 2006).

(CPRS & CTRS respectively).

Platon et al., 1990).

whole ADHD group with controls.

and is described only in older groups of ADHD patients.

**4.2 Excessive Daytime Sleepiness (EDS) and narcolepsy in ADHD** 

22%) could represent a strong bias in this study (Golan et al., 2004).

hypnagogic hallucinations and paralysis) in ADHD children.

modafinil, rather than the commonly used dopaminergic stimulants.

sections.

Children with Attention Deficit/Hyperactivity Disorder (ADHD) 35

Subsequently, Ryback et al. (2006) confirmed these results in 29 ADHD adults with an open

Interestingly, the reverse relationship does not appear to occur since ADHD symptoms are not commonly found in DSP. Therefore one might assume that SOI per se, as typical of DSP, is not enough to produce daytime feature of ADHD unless accompanied by nighttime

As for sleep maintenance insomnia (SMI), several primary sleep disorders such as obstructive sleep apnea syndrome (OSAS), periodic leg movement disorder (PLMD), and restless legs syndrome (RLS) concur in increasing wakefulness after sleep onset (WASO) with night-time awakenings and lowering sleep efficiency with related detrimental effects

These aspects will be developed later on in the course of this chapter, within their respective

Early morning insomnia is not typical of children with ADHD, unless severely depressed

As previously reported in this chapter, the "hypoarousal state" theory regarding ADHD claims that there may be decreased sleep oscillations (CAP) in ADHD children without major co-occurring sleep disorders, and this might explain their daytime drowsiness as confirmed by MSLT data and, indirectly, by the Epworth Sleepiness Scale (ESS) results in

On a modified version of MSLT, ADHD children were found to be objectively more sleepy than controls, albeit a higher rate of OSAS in probands with respect to controls (50% vs.

Also, Lecendreux et al. (2000) found a shorter mean sleep latency in ADHD children compared to controls, with a significant correlation to hyperactivity impulsivity and inattentive-passivity indexes, as measured by Conners Parent and Teacher rating scales

Differences in nocturnal sleep could not account for any of these results. None of these authors, however, sought for the instrumental hallmark of narcolepsy (2 Sleep onset REMs) in their studies, nor reported on the clinical secondary features of narcolepsy (cataplexy,

The fact that reaction time values in these studies (Lecendreux et al., 2000) hold a negative correlation with the hyperactivity-impulsivity index of the CPRS indicates that a major distinction must be drawn between IADHD and HADHD. Generally, only a subgroup of ADHD children are found to be sleepier than most average ADHD subjects, thus suggesting an impaired control of their arousal system, which may induce them to switch rapidly from wakefulness to sleep when insufficiently externally stimulated during daytime (Ramos

A consequent implication of this theory would be an improved therapeutic option through the employment of noradrenergic -1 agonists (Biederman & Spencer, 1999) such as

In a more recent study (Prihodova et al., 2010), SL on MSLT in unmedicated ADHD children exhibited significant time-related changes compared to the control group, but no intergroup differences were found regarding MSLT mean sleep latency when comparing the

hyperactivity/sleep fragmentation, as in most ADHD children (Walters et al., 2008).

spontaneous or event-related arousals in their subjects' PSG (Silvestri et al., 2009; O'Brien et al., 2003a), arousals have mostly not been formally identified or reported in ADHD PSG studies. Rather, an increased number of phase shifts has been reported (Miano et al., 2006) with the same clinical significance.

The only dedicated paper in terms of a formal approach to explore the microstructural aspects of sleep in ADHD has been written by Miano et al. (2006) who analyzed the cyclic alternating pattern (CAP) in ADHD children without abnormal AHI or PLMs index. The authors reported an overall reduction of CAP rate, an index of sleep instability, in comparison to normal controls, with ongoing reduction of CAP sequences and A1 index, reflecting hypersynchronous delta waves with a protective effect on sleep continuity. This paper would then reconcile the increased fragmentation and low efficiency seen by other authors in ADHD sleep, with the relative compensatory increase of A2 and A3 subtypes, expressing sleep discontinuity.

A striking CAP similarity between ADHD and narcolepsy (Ferri et al., 2005) has been observed along with increased daytime somnolence on multiple sleep latency tests (MSLT). The latter observation is of seminal importance for the interpretation of ADHD as a primary disorder of vigilance (Weinberg & Brumback, 1990). A deficit of the arousal level fluctuations would underlie the concept and clinical considerations which tend to interpret ADHD as "a hypoarousal state" despite its contradictory daytime paradoxical hyperactivity. Further detailing of this theory and related studies are to follow in the sleep disorders section under "Narcolepsy".
