J. Sleep Res.

(2011) 20, 338347 Sleep in children

doi: 10.1111/j.1365-2869.2010.00882.x

Sleep in children with autism with and without autistic regression

FLAVIA GIANNOTTI, FLAVIA CORTESI, ANTONELLA CERQUIGLINI,
C R I S T I N A V A G N O N I and D O N A T E L L A V A L E N T E
Center of Pediatric Sleep Disorders, Department of Developmental Neurology and Psychiatry, University of Rome La Sapienza, Italy

Accepted in revised form 25 June 2010; received 24 January 2010

SUMMARY The purpose of the present investigation was to characterize and compare traditional
sleep architecture and non-rapid eye movement (NREM) sleep microstructure in a well-
dened cohort of children with regressive and non-regressive autism, and in typically
developing children (TD). We hypothesized that children with regressive autism would
demonstrate a greater degree of sleep disruption either at a macrostructural or
microstructural level and a more problematic sleep as reported by parents. Twenty-two
children with non-regressive autism, 18 with regressive autism without comorbid
pathologies and 12 with TD, aged 510 years, underwent standard overnight multi-
channel polysomnographic evaluation. Parents completed a structured questionnaire
(Childrens Sleep Habits QuestionnaireCSHQ). The initial hypothesis, that regressed
children have more disrupted sleep, was supported by our ndings that they scored
signicantly higher on CSHQ, particularly on bedtime resistance, sleep onset delay,
sleep duration and night wakings CSHQ subdomains than non-regressed peers, and
both scored more than typically developing controls. Regressive subjects had
signicantly less ecient sleep, less total sleep time, prolonged sleep latency, prolonged
REM latency and more time awake after sleep onset than non-regressive children and
the TD group. Regressive children showed lower cyclic alternating pattern (CAP) rates
and A1 index in light sleep than non-regressive and TD children. Our ndings suggest
that, even though no particular dierences in sleep architecture were found between the
two groups of children with autism, those who experienced regression showed more
sleep disorders and a disruption of sleep either from a macro- or from a microstructural
viewpoint.
keywords autism, autistic regression, polysomnography, sleep, sleep architecture

disorder not otherwise specied. Other rare, very severe

INTRODUCTION
Autism spectrum disorders (ASD) are characterized by varying
degrees of impairment in communication skills, social interac-
tions and restricted, repetitive and stereotyped patterns of
behaviour, ranging from a severe form, called autism, to a
milder form, Asperger syndrome. If a child has symptoms of
either of these disorders, but does not meet the specic criteria
for either, the diagnosis is called pervasive developmental
Correspondence: Flavia Giannotti MD, Center of Pediatric Sleep
Disorders, Department of Developmental Neurology and Psychiatry,
University of Rome La Sapienza, Via dei Sabelli 108, 00185 Rome,
Italy. Tel.: +390644712219; fax: +39064957857; e-mail: avia.gian
notti@uniroma1.it
disorders that are included in the autism spectrum disorders
are Rett syndrome and childhood disintegrative disorder
(American Psychiatric Association, 2000). The precise neuro-
biological causes of autism and other ASD have yet to be
found, but some in cases genetic abnormalities have been
identied. In about one-third of children, autism becomes
apparent after a period of apparently normal or only relatively
delayed development, with as a loss of previously acquired
abilities (Davidovitch et al., 2000; Goldberg et al., 2003). The
main clinical features of this phenomenon, which has been
dened as autistic regression, is the loss of spoken language,
but social interests and other communicative skills are often
also aected. Regression typically takes place between 1 and

338  2010 European Sleep Research Society


3 years of age, with a peak around 24 months. Estimates of the
prevalence of this regressive pattern range between 15% and
40% of children with autism (Davidovitch et al., 2000;
Goldberg et al., 2003; Lord et al., 2004; Ozono et al., 2005;
Rice, 2007; Richler et al., 2006). Even though the mechanisms
underlying regression are still unknown, it has been postulated
that anatomical remodelling of the brain with synaptic growth
and pruning during the second year of life is impaired in
autism due to a gene-based mechanism (Carper and Cour-
chesne, 2005), resulting in a variable behavioural phenotype.
The core decits of autism and their underlying neurophys-
iology and neurochemistry may predispose children with ASD
to intrinsic stressors that threaten sleep. According to available
studies, sleep problems are endemic in children with ASD and
have been reported clinically in an estimated 4080% (Hering
et al., 1999; Honomichl et al., 2002; : Liu et al., 2006; Polimeni
et al., 2005; Schreck and Mulick, 2000; Wiggs, 2001). The
main clinical manifestations are resistance to go to bed at an
appropriate time, diculty in initiating sleep, frequent and
prolonged night-time awakenings or early morning awaken-
ings, irregularity in sleep wake pattern and poor sleep routines
(Giannotti et al., 2006; Krakowiak et al., 2008; Takase et al.,
1998; Williams et al., 2004).
In one of our previous studies, we found that over 50% of
children with autism had at least one sleep problem (Giannotti
et al., 2006), with a peak age of onset during the second year of
life, similar to what is known for autistic regression. The
remarkable temporal overlap between peak age of onset of
sleep problems and that of regression might be coincidental,
but could also be interpreted as the expression of a biologically
determined substrate which inuences a particular develop-
mental trajectory in critical phase of development. Addition-
ally, in a more recent questionnaire-based study, we found that
regressed children showed more disrupted sleep wake patterns
than non-regressed children (Giannotti et al., 2008). More
recently Wiggins et al. (2009), evaluating the phenomenon of
autistic regression using population-based data, reported that
regressed children showed more sleeping diculties than did
children with an ASD without documented regression.
Although conicting in some aspects, polysomnographic
studies have conrmed sleep disruption in children with ASD
quite consistently (Diomedi et al., 1999; Elia et al., 2000;
Limoges et al., 2005; Malow et al., 2006; Miano et al., 2007,
2008). In particular, a study on sleep architecture in autism
found normal rapid eye movement (REM) sleep percentage
and increased REM density (Elia et al., 2000), whereas a
signicant reduction of REM sleep, an increase of undieren-
tiated sleep and increased number of awakenings with a clear
abundance of spindle activity not only during Stage 2 non-
REM (NREM) sleep but also during slow wave sleep (SWS)
and REM sleep was reported by Diomedi et al. (1999). Other
investigators found longer sleep latency, more frequent awak-
enings, lower sleep eciency, increased duration of Stage 1
NREM sleep and decreased SWS as well as decreased density
of spindle activity in a group of high functioning adults with
autism (Limoges et al., 2005). In a study on children with
 2010 European Sleep Research Society, J. Sleep Res., 20, 338347
Sleep in autism 339
autism and severe mental retardation, Miano et al. (2007)
found reduced total sleep time and duration associated with
shorter REM latency. In contrast, Malow et al. (2006), in a
polysomnography (PSG) study on a group of selected children
with autism without mental retardation, found lower sleep
eciency, prolonged sleep latency, decreased REM sleep and
increased NREM Stages 34 and reported higher prevalence of
sleep problems compared to children with autism without sleep
problems and typically developing (TD) children.
Moreover, the microanalysis of the sleep electroencephalo-
gram (EEG) structure have led to the identication of the
cyclic alternating pattern (CAP) that provides a further
approach to the classication of sleep and amplies the
existing rules by Rechtschaen and Kales (1968), representing
a marker of instability of the sleep process. CAP consists in a
prolonged oscillation of the arousal level between two
reciprocal functional states termed phase A (greater arousal
level; cluster of EEG transient) and phase B (lesser arousal
level, interval between the successive clusters) and is considered
one of the elementary structures in the organization of NREM
sleep Terzano et al., 1985, 1988; Terzano and Parrino, 2000).
Using CAP analysis, Miano et al. (2007) found peculiarities in
sleep microstructure in children with autism characterized by a
low CAP rate associated with a low A1 index and a slight
increase of A2 and A3 subtypes, indicative of subtle alteration
of the arousal level of uctuations during NREM sleep.
The conicting data on sleep architecture in ASD might be
due to the heterogeneity in age, IQ and comorbidity with other
physical and psychological disorders, as well as the inclusion of
mixed diagnostic group in the same cohort that characterizes
the majority of the studies conducted. This emphasizes the
need for patients selection process based on more stringent
diagnostic criteria.
To the best of our knowledge, no studies specically
investigated sleep architecture of children with autism who
displayed regression. As a part of a larger study examining
sleep wake patterns in ASD, the purpose of the present
investigation was to characterize and compare traditional sleep
architecture and NREM sleep microstructure in a well-dened
cohort of children with regressive and non-regressive autism,
and in TD children. We hypothesized that children with
regressive autism would demonstrate a greater degree of sleep
disruption either at a macrostructural or microstructural level
and more problematic sleep as reported by parents. Further-
more, to avoid potential comorbid conditions and to enhance
patient compliance with the PSG study, we excluded subjects
with moderate to profound mental retardation.
METHODS
Participants
Participants were recruited from referrals to the developmental
disabilities speciality clinic of the Department of Developmen-
tal Neuropsychiatry over a 24-month period. Inclusion criteria
were: (1) clinical diagnosis of autistic disorder according to the
340 F. Giannotti et al.
Diagnostic and Statistical Manual of Mental Disorders, 4th
edition, Text Revision (DSM-IV TR) criteria (American
Psychiatric Association, 2000), conrmed by the Autistic
Diagnostic InterviewRevised 3rd edition (ADI-R) (Rutter
et al., 2003), and the Autism Diagnostic Observation Sche-
duleGeneric (ADOS-G) (Lord et al., 2000); (2) age between 5
and 10 years; (3) non-verbal IQ > 50 assessed by the Leiter
International Performance Scale with revised norms (Roid and
Miller, 1997); and (4) absence of other serious neurological,
psychiatric, bipolar disorder or medical conditions.
For all patients a detailed history was taken and full physical
and neurological examinations were performed. The absence
of associated pathologies was ascertained by a diagnostic
protocol, which included high-resolution banding karyotype,
brain magnetic resonance imaging and neurometabolic screen-
ing. Multi-modal evoked responses and prolonged awake and
sleep EEG were also performed to exclude the most frequently
associated conditions such as epilepsy, phenylketonuria, fragile
X syndrome or other chromosomal disorders, tuberous scle-
rosis, visual hearing or motor impairment and other structural
alterations of the central nervous system. No subjects with
autism were obese and the parents did not report snoring at the
time of the study. All subjects had a normal haematological
screening, were free of any infections, inammatory or allergic
reactions for at least 2 months prior to blood samplings and
were drug-free for at least 6 months prior to the beginning and
throughout the study. In order to exclude the associated
behaviours and psychiatric comorbidity seen frequently in
autistic disorder, parents, who were largely mothers, com-
pleted the Child Behavior Checklist (CBCL) (Achenbach and
Rescorla, 2000) during the initial screening. Children reporting
a T-score 70 on any of the syndrome scales and three
composite scores were not included in this study.
A non-convenience TD cohort was selected based on age
and gender recruited from area schools and recreation centres,
then screened for the absence of neurodevelopmental dis-
orders, including ASD, using the ADOS-G and the absence of
psychopathology on the basis of internalizing problems,
externalizing problems and total problems CBCL composite
scores.
According to inclusion criteria, a total of 42 subjects with
autism, selected from 130 patients with autism, and 12 TD
children were recruited for the study. Of the 78 children with
autism excluded, 19 suer from epilepsy, 25 showed EEG
abnormalities, 2 had tuberous sclerosis, 3 had fragile X
syndrome, 7 showed severe mental retardation and 22 showed
psychiatric comorbidity.
Children with autism were classied further according to
whether or not their parent had reported a history of loss of
skills (autistic regression) on the ADI-R. The occurrence of
regression is explored in two independent sections of the ADI-
R: language skill loss and general skill loss. The denition of
loss within the ADI-R is twofold: it requires that any loss be
coded only if the skill was established initially for at least
3 months, and the loss of skill must last at least 3 months. For
the specic features of the skill that were lost, each section
probes the intensity of the loss, the age when the loss was rst
apparent, the duration of the loss and the association with
physical illness. In order to be eligible for a loss of language
skills, it must be established that the child has attained
sucient language skills, such as the communicative use of at
least ve words on a daily basis. Children were classied as
regressed if they received a score of 1 on question 11 (loss of
at least ve words) and or 2 on question 20 (loss of general
skills) and or 2 on question 25 (probable or denite loss of
social interest and engagement). The loss of skills had to have
taken place before 36 months of age and lasted at least
3 months (Lord et al., 1994).
The presence of sleep disturbances was not a selection
criterion. However, children with breathing disturbances
during sleep were excluded clinically by investigating the
presence at least one of the following criteria: parental report
of snoring heavy or loud breathing, snoring more than half the
time, snoring loudly, trouble breathing, sleeping with open
mouth, congested nose at night, stopping breathing at night,
shaking sleeping child to breathe, awakening with a snoring
sound, physical examination investigating tonsillar hypertro-
phy and being overweight.
The nal sample consisted of three groups of children: one
with non-regressive autism [22 subjects, male sex 75%, mean
age 5.5 years, standard deviation (SD) 2.1], one with regressive
autism (18 subjects, male sex 80%, mean age 5.10 years, SD
3.9) and one with TD (12 subjects, male sex 75%, mean age
5.8 years, SD 2.4).
Informed written consent was obtained from the parents
of all participants to the study. The study was approved by
the Ethic Review Board of Rome University School of
Medicine.
Measures
The ADI-R is a semi-structured standardized parent interview
designed to assess the presence and severity of symptoms of
autism. An ADI-R diagnosis of autism is conferred on the
basis of an algorithm that distinguishes reliably children with
autism from those with other developmental delays or typical
development. A diagnosis of autism was assigned with scores
of 8 (7 if non-verbal), 10 and 3 for communication, social and
behaviour, respectively.
The ADOS-G is a semi-structured observational play-based
instrument, which discriminates between the narrower deni-
tion of autism and the broader PDD-NOS on the basis of
severity. Because not all children with autism were verbally
uent Module 1 or Module 2 were used, while Module 3 was
used for TD children. Diagnostic algorithm scores for
reciprocal social interaction and communication are calculated
with cuto values for Autism and Autistic Spectrum Disor-
ders. Items are scored from 0 (typical for age or not autistic in
quality) to 3 (unquestionably abnormal and autistic in
quality). Items are summed into a social communication
algorithm score that provides ranges for ASDs (711 points)
and autistic disorder (12 points).
 2010 European Sleep Research Society, J. Sleep Res., 20, 338347

The CBCL is a parentally completed questionnaire validated
in children aged 1.518 years, used to provide normative
values for domains of daytime behaviour in children. This
measure was chosen because is applicable for TD children or
with neurodevelopmental problems. The age-appropriate
module (1.55 years or 618 years) was completed by parents.
A T-score of 70 and above (at least 2 SD above the mean for
the general population) is generally considered to be clinically
signicant, and was used as the criterion for clinical signif-
icance in the present study.
Participants current level of non-verbal cognitive functioning
was evaluated using the Leiter International Performance Scale
with revised norms (Roid and Miller, 1997) for individuals
between 2 years and 20 years of age. TD children were admin-
istered individually one of the following standardized measures
of intellectual functioning. The Wechsler intelligence sca-
lesthe Wechsler Preschool and Primary Scale of Intelligence,
3rd edition (WPPSIIII) (Wechsler, 2008) and the Wechsler
Intelligence Scale for Children, 3rd edition (WISCIII) (Wechs-
ler, 2006)are standardized intelligence tests designed for indi-
viduals across the lifespan. In order to compare non-verbal
IQ more eectively, we considered WPSSI Performance IQ
and WISC Perceptual Reasoning Index for TD children.
The Childrens Sleep Habits Questionnaire (CSHQ) (Owens
et al., 2000) is a parent-completed questionnaire used in a large
number of studies to examine sleep behaviour in children. This
instrument has shown good psychometric properties and is
clinically useful for screening of sleep problems in TD children
at these young ages as well as in children with diverse
neurodevelopmental diagnoses. It includes items relating to a
number of key sleep domains grouped conceptually into eight
subscales reecting: (1) bedtime resistance; (2) sleep onset
delay; (3) sleep duration; (4) sleep anxiety; (5) night wakings;
(6) parasomnias; (7) sleep disordered breathing; and (8)
daytime sleepiness. In the present study CSHQ showed
adequate internal consistency in clinical and control groups
(Cronbachs alpha of 0.80 and 0.85, respectively). The alpha
coecients for CHSQ subscales ranged from 0.70 (night
wakings) to 0.91 (sleep disordered breathing) across all groups.
The sleep diary is a standardized weekly form that asks the
parent to note the specic sleep-related events on a daily basis:
times of sleep onset, awakenings from sleep, subsequent
returns to sleep, bedtime and waking times and times of day
naps.
Video-polysomnography
An overnight attended PSG for each participant was per-
formed in the sleep laboratory.
EEG recordings and electrode placement were performed
according the 1020 International System and the PSG
montage included at least 11 EEG channels (Fp1, Fp2, C3,
C4, Cz, P3, P4, T3, T4, O1, O2) referenced to contralateral
mastoid, left and right electroculogram (EOG), chin electro-
myogram (EMG), left and right tibialis anterior EMG and
electrocardiogram (ECG), one derivation. Infrared EEG-
 2010 European Sleep Research Society, J. Sleep Res., 20, 338347
Sleep in autism 341
synchronized video monitoring and a sensitive intercom were
also used. Analogue electrophysiological signal was digitized
using a commercially available PSG system (Embla N7000
and Somnologica Software; Medcare Flaga hf., Reykjavik,
Iceland) and video recording were acquired synchronously to
the EEG data. The data were digitized with a sampling rate of
256 Hz. Then, sleep signals with duration of 30 s were stored
on hard disk in European data format (Kemp et al., 1992). The
measured EEG signals were rst acquired with a wide-band
analogue lter (0.001)70 Hz) and then digitally band-pass
ltered at 0.1)50 Hz.
Procedures
All parents completed the CSHQ, and in order to obtain a
measure of the childs habitual bedtime and wake time sleep
diaries were collected for 1 week prior to the laboratory PSGs.
Parents were invited to record the diary for the previous 24 h
each morning after the child awakened.
All children underwent PSG multi-channel polysomnogra-
phy for two consecutive nights in the laboratory in order to
avoid the rst-night eect. No sedation or sleep deprivation
was used to induce sleep. Children were instructed to avoid
products containing caeine during the week prior to the PSG
study. All recordings started at the patients usual bedtime and
continued until spontaneous awakening. To alleviate separa-
tion anxiety, the parent slept in a bed next to their child.
Analysis of polysomnographic recordings
Sleep macrostructure. Sleep was subdivided into 30-s epochs
and sleep stages were scored according to the standard
criteria by Rechtschaen and Kales (1968), following the
recommendation made by Scholle and Schafer (1999). The
following conventional sleep parameters were evaluated: time
in bed (TIB); total sleep time (TST): the time from sleep onset
to the end of the nal sleep epoch minus time awake; sleep
eciency (SE%): the percentage ratio between total sleep
time and time in bed (TST TIB 100); sleep latency (SL):
the start of three consecutive epochs Stage 1 or the rst epoch
of any deeper sleep stage in minutes; REM latency: time from
sleep onset to the rst stage REM epoch; wake after sleep
onset (WASO) expressed in minutesnumber of stage
shifts h (SS h); number of awakenings h (AWN h); per-
centage of TST spent in stage WASO (W%) and in sleep
stage 1 (NREM 1%), Stage 2 (NREM 2%), SWS% and
Stage REM (REM%).
Periodic leg movements during sleep (PLMS) were detected
following the recent criteria established by the American
Academy of Sleep Medicine (AASM) (Iber et al., 2007). PLMS
were dened as a sequence of four or more limb movements of
0.55.0 s in duration that were separated by more than 5 s and
less than 90 s and the amplitude of which was greater than or
equal to 25% of toe dorsiexion during calibration. The
PLMS index was calculated by dividing the number of PLMS
by the total number of hours of sleep (AASM, 2005). To avoid
342 F. Giannotti et al.
the rst-night eect, only the results from the second night
were included in the analyses.
Sleep microstructure. CAP was scored according to the
currently accepted criteria (Bruni et al., 2002, 2005; Terzano
et al., 2001), as shown in Table 1.
A CAP is formed by electrocortical events indicated by
periodic EEG activity occurring during NREM sleep and
characterized by transitory events that recur at regular
intervals in the range of seconds during NREM sleep. These
events are clearly distinct from the background EEG rhythm
as abrupt frequency shifts or amplitude changes.
The following CAP parameters were evaluated: CAP rate
(percentage of total NREM sleep time occupied by CAP
sequences); percentage and duration of each A phase subtype;
A1 index (number of phase A1 per hour of NREM sleep and
of Stage 1, Stage 2 and SWS sleep stages; A2 index (number of
phase A2 per hour of NREM sleep and of Stage 1, Stage 2 and
SWS sleep stages; A3 index (number of phase A3 per hour of
NREM sleep and of Stage 1, Stage 2 and SWS sleep stages;
duration of B phases; and number and duration of CAP
sequences. All these variables were analysed by means of the
Hypnolab version 1.2 sleep software analysis (SWS Soft,
Troina, Italy). All the recordings were scored visually. For the
purposes of the current research, all recordings were rescored
by three expert scorers (F.G., F.C., C.V.) blinded to subject
identity and health status. A randomly chosen primary scorer
identied CAP events, on the basis of predened criteria. A
second scorer reviewed this initial scoring. When there was a
discrepancy for any event, a third scorer reviewed the
questionable event and the majority score was used. Sleep
parameters derived were tabulated for statistical analysis. Of
the total participants who met inclusion criteria, two were
excluded from the analysis because of electrode artefact or
equipment malfunction.
Table 1 Cyclic alternating pattern (CAP) scoring criteria
Transient events
abrupt EEG shiftslow or fastfrom the sleep
electroencephalogram (EEG) background activity
duration of events: lasting more than 2 and less than 60 s
Phase A
A1 synchronized EEG patterns (intermittent alpha rhythms and
sequence of vertex sharp waves in Stage 1; sequence of two or
more K-complexes in Stage 2 and delta bursts in slow wave
sleep (SWS)
A2 desynchronized EEG patterns preceded by slow high voltages
waves (K complexes with alpha or beta rhythms)
A3 desynchronized EEG patterns alone
Phase B
EEG background activity according to each sleep stage
CAP cycle
Each cycle consists of a phase A and a phase B lasting between
2 and 60 s
CAP sequence
Two or more CAP cycles beginning with a phase A and ending
with a phase B
Statistical analysis
All data were coded and computerized with statistical analysis
performed using statistica version 6 package for Windows
(StatSoft Inc., Tulsa, OK, USA). Descriptive statistics (means,
SD) were calculated for all continuous variables and frequen-
cies were generated for non-continuous variables. Unpaired
Students t-test or Pearsons chi-square test were used to test
for group dierences as appropriate. Multivariate statistics
[analysis of covariance (ancova)] included health status
(regressed, non-regressed, TD), as between-subjects factor
were performed on PSG variables, controlling for age. We
conducted post hoc multiple pairwise comparisons using the
Schee tests to control for overall Type 1 error and to
determine which group comparisons were signicant across
variables.
Because distributions were positively skewed for most
variables, a log-transform was applied to variables whose
skewness statistics was greater than twice the standard error
(these included all but the following: Stage 2, Stage 4 and
SWS). Group dierences were also compared by eect size,
measured by eta-squared (g2), a measure of contrast between
groups independent of sample size (Olejnik and Algina,
2003). The P level was set at <0.05 for statistical
signicance.
RESULTS
The nal sample consisted of three groups of children: one
with non-regressive autism (22 subjects, male sex 75%, mean
age 5.5 years, SD 2.1), one with regressive autism (18
subjects, male sex 80%, mean age 5.10 years, SD 3.9) and
one with TD (12 subjects, male sex 75%, mean age 5.8 years
SD 2.4).
Among the children with ASD group, 25 had a mild mental
retardation and 15 other subjects showed borderline intellec-
tual functioning. All TD children showed normal intellectual
functioning.
Regressed and non-regressed children did not dier in their
Leiter-R Brief IQ [61.35, SD 20.30 versus 66.12, SD 24.05; not
signicant (NS)]. In the regressive group the average age at
which parents reported the main loss of skills was 20 months
(range 1230 months; SD 4.86).
Among children with regression, language loss was noted in
74%, social skills losses were noted in 17% of records and
general losses were noted in 9%.
Scores for CSHQ variables and from the sleep diary are
presented in Table 2. Analysis of sleep diaries showed that
children in the regressed group woke more frequently during
the night than non-regressed, and the average time they spent
awake during the night was signicantly longer. Several
children in the regressed group were awake for periods of
1 h or more and slept for a signicantly shorter length of time
(P < 0.001). Furthermore, children in the regressed group
were found to have signicantly longer sleep latency than
children in the non-regressed group. Lights were turned o for
 2010 European Sleep Research Society, J. Sleep Res., 20, 338347
 Sleep in autism 343

Table 2 Sleep variables and Childrenss Sleep Habits Questionnaire (CSHQ) subscales scores children with autism (non-regressed and regressed)
and typically developing children

Non-regressed Regressed TD

Sleep variables Mean (SD) (n = 22) Mean (SD) (n = 18) Mean (SD) (n = 12) F-value for group eect P

Bedtime (hh:mm) 22.15 (1.07) 23.30 (1.12) 21.30 (0.50) 100.42 <0.001abc
Rise time (hh:mm) 07.20 (1.26) 7.00 (1.24) 7.15 (0.26) 5.41 <0.01bc
Sleep length (min) 530 (86) 430 (95) 580 (46) 88.90 <0.001abc
Sleep latency (min) 31.23 (30.56) 40.51 (28.88) 12.59 (5.08) 42.86 <0.05a <0.001bc
CSHQ subdomains scores
Bedtime resistance 10.10 (3.42) 13.8 (3.00) 7.20 (2.10) 102.01 <0.001abc
Sleep onset delay 1.70 (0.92) 2.40 (0.9) 1.00 (0.29) 70.14 <0.001abc
Sleep duration 4.73 (2.35) 6.50 (2.40) 3.10 (0.20) 75.38 <0.001abc
Sleep anxiety 4.90 (2.10) 4.70 (2.89) 4.68 (0.99) 0.44 NS
Night-wakings 4.40 (1.76) 6.90 (1.77) 3.10 (0.57) 93.91 <0.001abc
Parasomnias 8.10 (1.73) 8.20 (2.50) 7.90 (1.10) 0.98 NS
Sleep disordered breathing 3.31 (0.88) 3.30 (0.99) 3.20 (0.89) 0.91 NS
Daytime sleepiness 10.10 (2.51) 10.20 (3.90) 9.92 (2.90) 0.90 NS

One-way analysis of covariance for continuous variables controlled for age. NS, not signicant. aNon-regressed versus regressed; bnon-regressed
versus typically developing (TD); cregressed versus TD.

sleep signicantly later and children in the regressed group fell

asleep at a signicantly later time. Moreover, regressed
children woke up about 20 min earlier than non-regressed
children. Post hoc contrast analyses showed that regressed
children had signicantly higher CSHQ total scores than non-
regressed autistic children, and both groups scored more than
typically developing controls (respectively, 55.6 versus 48.6
versus 39, one-way ancova, F(2.25) = 85.78; P < 0.001).
Regressed children showed signicantly higher scores on
bedtime resistance, sleep onset delay, sleep duration and night
wakings CSHQ subdomains than non-regressed children and,
as expected, both more than TD children, while no signicant
dierences were found for sleep anxiety, parasomnias, sleep-
iness and sleep disordered breathing CSHQ subdomains across
all groups.
Sleep macrostructure
ancovas were conducted to assess between-group dierences in
sleep architecture (Table 3).
These analyses revealed a signicant group main eect for
almost all sleep variables. The eect size was modest to large,
with g2 of 0.77 for decreased of slow wave sleep, indicating that
autism itself accounted for 77% of the overall variance of this
variable. Sleep eciency, total sleep time, sleep latency and
stage NREM Stage 2 had a less prominent but still sizeable
eect. Within-group post hoc analyses indicated that children
with regressive autism had signicantly less ecient sleep,
decreased total sleep time, prolonged sleep latency, prolonged
REM latency and more percentage of time awake after sleep
onset than the children with non-regressive autism and TD

Table 3 Polysomnographic macrostuctural data in children with autism (non-regressed and regressed) and typically developing children

Non-regressed Regressed TD

Mean (SD) (n = 22) Mean (SD) (n = 18) Mean (SD) (n = 12) F P g2 Post hoc

TST (min) 525.20 (52.73) 451.30 (58.30) 610.20 (66.38) 29.10 <0.001 0.48 a,b,c
SE (%) 84.18 (6.95) 74.55 (8.56) 94.70 (2.77) 28.70 <0.001 0.46 a,b,c
SL (min) 35.25 (18.77) 53.10 (24.60) 20.40 (5.47) 15.94 <0.05 0.35 a,b,c
WASO (%) 9.55 (5.43) 15.90 (9.31) 2.10 (2.75) 17.56 <0.001 0.38 a,b,c
AWN h 1.98 (1.51) 3.34 (2.35) 0.36 (0.19) 7.30 <0.01 0.18 b,c
REM L (min) 154.02 (97.74) 198.91 (101.51) 99.65 (21.21) 10.05 <0.01 0.22 b,c
Stage 1% 9.12 (4.74) 8.96 (9.57) 7.25 (1.08) 1.05 NS 0.02 NS
Stage 2% 47.65 (5.47) 54.50 (8.02) 41.30 (2.38) 15.91 <0.001 0.40 c
SWS% 19.35 (4.93) 12.89 (3.11) 26.67 (2.03) 15.55 <0.001 0.77 c
REM (%) 14.70 (6.56) 7.75 (5.62) 22.68 (1.60) 5.05 <0.01 0.18 c
SS h 10.42 (4.43) 10.13 (6.98) 8.55 (3.07) 4.14 <0.5 0.08 NS

One-way analysis of covariance controlled for age. TST, total sleep time; SL, sleep latency; SWS, slow wave sleep; REM L, rapid eye movement
(REM) latency; SS h, stage shifts per hour; AWN h, awakenings per hour; SD, standard deviation; SE, sleep efciency; WASO, wake after
sleep onset; g2 is the effect size; anon-regressed versus regressed; bnon-regressed versus typically developing (TD); cregressed versus TD; NS, not
signicant.

 2010 European Sleep Research Society, J. Sleep Res., 20, 338347

344 F. Giannotti et al.

groups. Moreover, children with autism and developmental
regression showed a statistically signicant lower time in REM
and in NREM SWS and higher in NREM 2 sleep compared to
TD children. Also stage shifts were slightly increased (without
statistical signicance) in both groups with autism. All children
had a periodic leg movement index (PLMI) with values <5
(non-regressive autism 1.4 1.2; regressive autism 1.5 0.9;
TD 1.2 0.8; NS).
Sleep microstructure
CAP analysis results (Table 4) revealed that both groups with
autism had lower total A1 percentages and increased A2 and
A3 percentages than TD children.
It is to be noted that in this case the eect size was modest to
large, which means that autism itself accounted for 80% (low
A1 percentage), 58% (increased A2 percentage) and 55%
(increased A3 percentages) of the overall (eect+error)
variance. These ndings were statistically signicantly more
evident in children with regression. Post hoc comparison
analyses showed that children with regressive autism had a
lower total CAP rates and lower CAP rates during Stages 1
and 2 sleep than TD children and signicantly reduced CAP
rates during Stage 2 sleep than children with non-regressive
autism. This latter group showed a lower CAP rate than TD
children only during Stage 2. In particular, a lower A1 index
was found in light sleep as well as an increased A2 and A3
index in children with autism and regression.
DISCUSSION
To the best of our knowledge, this study represents the rst
attempt to evaluate sleep architecture in subgroups of children
with narrowly dened autism without other coexistent pathol-
ogies. Consistent with our hypothesis, this study has suggested
that a history of autistic regression is associated strongly with
disrupted sleep. The ndings we present reinforce the idea of a
marked alteration of sleep pattern in children with regressive
autism. Notwithstanding that the type of sleep alterations did
not dier from those reported by children with non-regressive
autism, consisting mainly in decreased total sleep time,
prolonged sleep latency, prolonged REM latency, less per-
centage time in REM, less percentage time in SWS, more time
in NREM 2 sleep and more WASO in both groups, regressed
children showed a more severe sleep alteration.
Data from previous PSG studies in children with autism
are controversial. In particular, Aihara and Hashimoto
(1986), reporting a similar amount of REM sleep in children
with autism and normal controls, observed an abnormal
presence of spindling-like activity during REM and the
presence of rapid eye movements during light sleep, suggest-
ing a defect of maturational process in these children. Elia

Table 4 Polysomnographic microstructural data in children with autism (non-regressed and regressed) and typically developing children

Non-regressed Regressed TD

Mean (SD) (n = 22) Mean (SD) (n = 18) Mean (SD) (n = 12) F P g2 Post hoc

Total CAP rate (%) 31.28 (5.20) 27.12 (4.60) 34.45 (5.40) 3.25 <0.5 0.10 c
In S1 (%) 17.68 (14.13) 12.24 (11.27) 22.67 (1.50) 3.15 <0.5 0.11 c
In S2 (%) 18.28 (5.90) 14.22 (8.10) 25.34 (5.34) 8.15 <0.01 0.25 a,b,c
In SWS (%) 40.55 (13.74) 42.34 (15.53) 45.88 (2.90) 1.05 NS 0.03 NS
A1 (%) 55.20 (4.33) 45.65 (3.17) 72.53 (2.04) 102.03 <0.001 0.80 a,b,c
A2 (%) 24.24 (2.87) 27.97 (1.21) 14.07 (0.82) 52.92 <0.01 0.58 a,b,c
A3 (%) 20.46 (5.10) 26.38 (3.31) 13.50 (1.78) 30.19 <0.001 0.55 a,b,c
A1 duration (s) 5.10 (0.25) 5.00 (0.30) 6.18 (0.38) 25.26 <0.01 0.45 b,c
A2 duration (s) 6.15 (0.80) 5.92 (1.21) 8.45 (0.88) 30.00 <0.01 0.56 b,c
A3 duration (s) 14.65 (2.20) 15.60 (1.71) 16.41 (1.02) 4.05 <0.05 0.15 c
A1 index 25.56 (8.45) 21.45 (8.20) 30.87 (8.01) 4.25 <0.01 0.30 c
In S1 18.30 (12.57) 10.55 (8.96) 21.28 (8.49) 3.18 <0.5 0.10 c
In S2 25.14 (8.10) 17.22 (8.04) 30.88 (12.25) 8.05 <0.01 0.40 c
In SWS 62.27 (22.97) 61.45 (25.42) 62.71 (4.55) 0.25 NS 0.01 NS
A2 index 5.22 (2.22) 5.81 (2.16) 4.58 (0.74) 0.88 NS 0.04 NS
In S1 4.22 (3.05) 14.45 (3.17) 3.28 (2.97) 27.28 <0.01 0.45 b,c
In S2 14.56 (9.89) 12.45 (6.69) 8.44 (2.78) 4.05 <0.5 0.11 b,c
In SWS 3.75 (2.38) 2.35 (3.56) 5.38 (1.31) 4.00 <0.05 0.10 c
A3 index 4.90 (2.45) 5.45 (3.04) 4.00 (0.44) 1.05 NS 0.05 NS
In S1 17.08 (6.90) 19.24 (10.04) 11.32 (9.37) 3.89 <0.5 0.14 c
In S2 6.72 (3.78) 7.88 (4.37) 6.72 (0.85) 0.95 NS 0.02 NS
In SWS 4.79 (2.24) 5.09 (2.22) 2.96 (0.51) 6.05 <0.01 0.18 b,c
B duration (s) 22.16 (2.86) 21.88 (2.46) 23.95 (0.77) 4.05 <0.01 0.14 c
Sequence duration (s) 168.58 (36.43) 159.55 (30.20) 182.98 (31.35) 1.98 NS 0.04 NS
No. of sequences 46.34 (10.36) 48.45 (9.60) 37.25 (3.29) 17.95 <0.01 0.44 b,c

CAP, cyclic alternating pattern; S1, Stage 1; S2, Stage 2; SWS, slow wave sleep; g2, effect size; anon-regressed versus regressed, bnon-regressed
versus typically developing (TD); cregressed versus TD; NS, not signicant.

 2010 European Sleep Research Society, J. Sleep Res., 20, 338347


et al. (2000) reported a reduced total sleep time, a normal
percentage of sleep NREM stages and REM sleep and a
decreased latency to rst REM period. Diomedi et al. (1999)
found an increased number of interspersed wakefulness and
awakenings, increased undierentiated sleep, reduced REM
sleep, fragmentation of REM period due to frequent intru-
sion of NREM sleep, increased REM density and more
latency to the rst REM sleep episode. Consistent with
results of the latter study we found reduced REM sleep, but
also a prolonged latency to rst REM episode, mainly in
regressed children with autism. Conversely, Miano et al.
(2007) did not nd any dierence in percentage of NREM
stages and REM sleep, but only a shorter sleep time and rst
REM latency compared to controls in a sample of children
with autism and mental retardation.
The literature commonly emphasized the importance of a
relationship between REM sleep and intellectual functioning:
the greater the level of mental retardation, the lower the
amount of REM sleep (Castaldo and Krynicki, 1973; Espie
et al., 1998). However, many studies suggested that sleep
patterns of children with autism dier from other develop-
mental disabilities (Krakowiak et al., 2008; Richdale and
Prior, 1995). In the study by Diomedi et al. (1999), which
compared sleep patterns of dierent developmental disabilities,
children with autism showed less REM sleep and more
undierentiated sleep even though the level of mental retar-
dation was consistent across groups. Similarly, in the current
study regressed children showed more disrupted sleep patterns
than those without regression, even though the level of mental
retardation did not dier signicantly between the groups. On
the basis of our ndings, it is quite plausible that children with
autism, mainly those who displayed regression, suer from an
intrinsic sleep problem that could be related to an underlying
pathophysiology of this disorder. Several neurotransmitter
systems, including gamma aminobutyric acid, serotonin and
melatonin, implicated in promoting sleep and establishing a
regular sleep wake cycle, are aected by autism, and their
aberration in autism may be responsible for a component of
the prevalent sleep alterations (Levitt et al., 2004). Develop-
mental abnormalities of serotonin synthesis have been dem-
onstrated in children with autism consisting in increased level
of synthesis capacity and asymmetry of serotonin production
(Chandana et al., 2005; Chugani et al., 1999). As already
reported by Elia et al. (2000), the reduction of total sleep time
might be a consequence of dysfunction of the brainstem
aminergic pathways. A failure in the development of the
circadian sleep wake cycle due to failure to entrain to the
day night cycle has been suggested (Segawa and Nomura,
2006). This failure implicates involvement of 5 HT neurones
among ascending brainstem monoaminergic neurones that
modulate the development of the circadian sleep wake cycle
(Tordjman et al., 2005).
Sleep microstructural analysis results complement those of
macrostructural analysis, conrming sleep alterations. Parti-
cularly, in agreement with Miano et al. (2007) we found a low
CAP rate associated with a low A1 index and a slight increase
 2010 European Sleep Research Society, J. Sleep Res., 20, 338347
Sleep in autism 345
of A2 and A3 subtypes in children with autism and develop-
mental regression. It has been reported widely that A1
subtypes are indicative of neuronal mechanism for NREM
sleep maintenance while subtypes A2 and A3 are the expres-
sion of NREM sleep disruption (Terzano and Parrino, 2000).
In the build-up to and maintenance of deep sleep, activation
events are composed basically of subtypes A1, which could
play an important role in protecting sleep continuity from light
sleep to deep sleep. However, in contrast to that reported by
Miano et al. (2007), who found the low A1 percentage in SWS,
we found it only during light sleep. It must be noted that in this
study Miano et al. (2007) also included children with severe
mental retardation, who represent more than half of their
patients, while in our study we excluded children with an IQ
lower than 50. As already stated, SWS represents a crucial
component of the hypothesized synaptic downscaling during
sleep, probably important for the cognitive processing (Ferini-
Strambi et al., 2004; Ferri et al., 2008); thus, as stated by
Miano et al. (2007) the reduction of A1 in SWS in their sample
might be related to the degree of mental retardation. In
agreement with this hypothesis, a more recent study (Miano
et al., 2008) found a reduction of A1 in SWS in subjects with
Down syndrome and fragile X syndrome, conrming that this
alteration might be related to the level of mental retardation.
Moreover, another dierence between our study and that of
Miano et al. (2007) regards the childrens age, which we have
kept within a narrow range in consideration of the age-
dependency of CAP parameters (Bruni et al., 2002, 2005).
The low CAP rate with a attention decit hyperactive
disorder (ADHD) lower amount of A1 during light sleep
found in our study has already been described in children with
(Miano et al., 2006), and it might therefore not be considered a
specic feature but an expression of a dysregulation of arousal
level of uctuations during NREM sleep, particularly evident
in, but not exclusive to, children with autism and regression.
Some limitations of the study should be taken into account.
Even though we did not include children with respiratory
disturbances, habitual snoring or with obesity, we are not
able to exclude polysomnographically the presence of sleep
breathing disorders, as we did not record respiratory param-
eters in order to improve PSG compliance. Moreover, even
though we did not include children with moderate and severe
mental retardation, our sample also included patients aected
by mild mental retardation, thus we cannot state whether the
alteration of sleep macro- and microstructure are characteristic
of autism or related to mental retardation. Finally, it may be
argued that the high rate of children reporting sleep problems
in our sample might be responsible for the PSG sleep alteration
we found. In a recent PSG study on a group of selected
children with autism without mental retardation, Malow et al.
(2006) found a lower sleep eciency, prolonged sleep latency,
decreased REM sleep and increased SWS only in children with
autism reporting sleep problems compared to children with
autism without sleep problems and TD children.
Taken together, our ndings suggest that, even though no
particular dierences in sleep architecture were found between
346 F. Giannotti et al.
the two groups of children with autism, those with a history of
autistic regression showed more disrupted sleep either from a
macro- or a microstructural viewpoint. NREM microstructure
alterations associated with the reduction of REM and SWS
percentage and an increase of NREM 2 sleep seem more
evident in children with autism and regression. Mechanisms
underlying autistic regression and sleep problems in children
with autism are still unknown, and further studies are needed
to evaluate sleep more eectively in a larger sample of selected
subgroups of children with autism without mental retardation
and clinically reported sleep disorders.
REFERENCES
Achenbach, T. M. and Rescorla, L. A. Manual for the ASEBA School-
Age Forma and Proles. University of Vermont Research Center for
Children, Youth, & Families, Burlington, VT, 2000.
Aihara, R. and Hashimoto, T. Sleep polygraphic and neuroendocri-
nological studies on autistic children. Brainstem Telencephalon.
Behav., 1986, 2943.
American Academy of Sleep Medicine. International Classication of
Sleep Disorders: Diagnostic and Coding Manual, 2nd edn. American
Academy of Sleep Medicine, Westchester, IL, 2005.
American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders, 4th edn. Text Revision. American Psychiatric
Association, Washington, DC, 2000
Bruni, O., Ferri, R., Miano, S. et al. Sleep cycling alternating pattern in
normal school-age children. Clin. Neurophysiol., 2002, 113: 18061814.
Bruni, O., Ferri, R., Miano, S. et al. Sleep Cycling alternating pattern
in normal preschool-aged children. Sleep, 2005, 28: 220230.
Carper, R. A. and Courchesne, E. Localized enlargement of the frontal
cortex in early autism. Biol. Psychiatry, 2005, 57: 126133.
Castaldo, V. and Krynicki, V. Sleep pattern and intelligence in
functional mental retardation. J. Ment. Dec. Res., 1973, 17: 231235.
Chandana, S. R., Behen, M. E., Juhasz, C. et al. Signicance of
abnormalities in developmental trajectory and asymmetry of cortical
serotonin synthesis in autism. Int. J. Dev. Neurosci., 2005, 23: 171182.
Chugani, D. C., Muzik, O., Behen, M. et al. Developmental changes in
brain serotonin synthesis capacity in autistic and nonautistic
children. Ann. Neurol., 1999, 45: 287295.
Davidovitch, M., Glick, L., Holtzman, G., Tirosh, E. and Sar, M. P.
Developmental regression in autism: maternal perception. J. Autism
Dev. Disord., 2000, 30: 113119.
Diomedi, M., Curatolo, P., Scalise, A., Pacidi, F., Caretto, F. and
Gigli, G. L. Sleep abnormalities in mentally retarded autistic
subjects: Downs syndrome with mental retardation and normal
subjects. Brain Dev., 1999, 21: 548553.
Elia, M., Ferri, R., Musumeci, S. A. et al. Sleep in subjects with
autistic disorders: a neurophysiological and psychological study.
Brain Dev., 2000, 22: 8892.
Espie, C. A., Paul, A., McFie, J. et al. Sleep studies of adults with
severe or profound mental retardation and epilepsy. Am. J. Ment.
Retard., 1998, 103: 4759.
Ferini-Strambi, L., Ortelli, P., Castronovo, V. and Cappa, S. Increased
periodic arousal uctuations during NREM sleep are associated to
superior memory. Brain Res. Bull., 2004, 63: 439442.
Ferri, R., Huber, R., Arico`, D. et al. The slow-wave components of the
cyclic alternating pattern (CAP) have a role in sleep-related learning
processes. Neurosci. Lett., 2008, 432: 228231.
Giannotti, F., Cortesi, F., Cerquiglini, A. and Bernabei, P. An open-
label study of controlled-release melatonin in treatment of sleep
disorders in children with autism. J. Autism Dev. Disord., 2006, 36:
741752.
Giannotti, F., Cortesi, F., Cerquiglini, A. et al. An Investigation of
sleep characteristics, EEG abnormalities and epilepsy of develop-
mentally regressed and non-regressed autistic children. J. Autism
Dev. Disord., 2008, 38: 18881897.
Goldberg, W. A., Osann, K., Filipek, P. A. et al. Language and other
regression: assessment and timing. J. Autism Dev. Disord., 2003, 33:
607616.
Hering, E., Epstein, R., Elroy, S., Iancu, D. R. and Zelnik, N. Sleep
patterns in autistic children. J. Autism Dev. Disord., 1999, 29: 143147.
Honomichl, R. D., Goodlin-Jones, B. L., Burnham, M., Gaylor, E.
and Anders, T. F. Sleep patterns of children with pervasive
developmental disorders. J. Autism Dev. Disord., 2002, 32: 553561.
Iber, C., Ancoli-Israel, S., Chesson, A. L. and Quan, S. F. The AASM
Manual for the Scoring of Sleep and Associated Events: Rules,
Terminology, and Technical Specications, 1st edn. American Acad-
emy of Sleep Medicine, Westchester, IL, 2007.
Kemp, B., Varri, A., Rosa, A. C., Nielsen, K. D. and Gade, J. A simple
format for exchange of digitized polygraphic recordings. Electroen-
cephalogr. Clin. Neurophysiol., 1992, 82: 391393.
Krakowiak, P., Goodlin-Jones, B., Hertz-Picciotto, I., Croen, L. A.
and Hansen, R. L. Sleep problems in children with autism spectrum
disorders, developmental delays, and typical development: a popu-
lation-based study. J. Sleep Res., 2008, 17: 197206.
Levitt, P., Eagleson, K. L. and Powell, E. M. Regulation of neocortical
interneuron development and the implications for neurodevelop-
mental disorders. Trends Neurosci., 2004, 27: 400406.
Limoges, E., Mottron, L., Bolduc, C., Berthiaume, C. and Godbout,
R. Atypical sleep architecture and the autism phenotype. Brain,
2005, 128: 10491061.
Liu, X., Hubbard, J. A., Fabes, R. A. and Adam, J. A. Sleep
disturbances and correlates of children with autism spectrum
disorders. Child Psychiatr. Hum. Dev., 2006, 37: 179191.
Lord, C., Rutter, M. and Le Couteur, A. Autistic Diagnostic
InterviewRevised: a revised version of a diagnostic interview for
caregivers of individuals with possible pervasive developmental
disorders. J. Autism Dev. Disord., 1994, 24: 659685.
Lord, C., Risi, S., Lambrecht, L. et al. The Autism Diagnostic
Observation ScheduleGeneric: a standard measure of social and
communication decits associated with the spectrum of autism.
J. Autism Dev. Disord., 2000, 30: 205223.
Lord, C., Shulman, C. and DiLavore, P. Regression and word loss in
autistic spectrum disorders. J. Child Psychol. Psychiatry, 2004, 45:
936955.
Malow, B. A., Marzec, M. L., McGrew, S. G., Wang, L., Henderson,
L. M. and Stone, W. L. Characterizing sleep in children with autism
spectrum disorders: a multidimensional approach. Sleep, 2006, 29:
15631571.
Miano, S., Donfrancesco, R., Bruni, O. et al. NREM sleep instability
is reduced in children with attention-decit hyperactivity disorders.
Sleep, 2006, 29: 797803.
Miano, S., Bruni, O., Elia, M., Trovato, A., Smerieri, A. and Verrillo,
E. Sleep in children with autistic spectrum disorder: a questionnaire
and polysomnographic study. Sleep Med., 2007, 9: 6470.
Miano, S., Bruni, O., Elia, M. et al. Sleep phenotypes of intellectual
disability: a polysomnographic evaluation in subjects with Down
syndrome and fragile X syndrome. Clin. Neurophysiol., 2008, 119:
12421247.
Olejnik, S. and Algina, J. Generalized eta and omega squared statistics:
measures of eect size for some common research designs. Psychol.
Methods, 2003, 8: 434447.
Owens, J. A., Spirito, A. and McQuinn, M. The Childrens Sleep
Habits Questionnaire. Psychometric properties of a survey instru-
ment for school-aged children. Sleep, 2000, 23: 10431051.
Ozono, S., Williams, B. J. and Landa, R. Parental report of the early
development of children with regressive autism: the delays-plus-
regression phenotype. Autism, 2005, 9: 461486.
 2010 European Sleep Research Society, J. Sleep Res., 20, 338347

Polimeni, M. A., Richdale, A. L. and Francis, A. J. A survey of sleep
problems in autism, Aspergers disorder and typically developing
children. J. Intellect. Disabil. Res., 2005, 49: 260268.
Rechtschaen, A. and Kales, A. A Manual of Standardized Terminol-
ogy, Techniques, and Scoring System for Sleep Stages of Human
Subjects. Washington Public Health Service, US Government
Printing Oce, Washington, DC, 1968.
Rice, C. Prevalence of Autism Spectrum DisordersAutism and Devel-
opmental Disabilities Monitoring Network, Six Sites, United States,
2000, 2007(2007, February 9 56(SS01); 111). Available at: http://
www.cdc.gov/mmwr/preview/mmwrhtml/ss5601a1.htm (accessed 15
June 2009).
Richdale, A. L. and Prior, M. R. The sleep wake rhythm in
children with autism. Eur. Child Adolesc. Psychiatry, 1995, 4:
175186.
Richler, J., Luyster, R., Risi, S. et al. Is there a Regressive Phenotype
of autism spectrum disorder associated with the measlesmumps
rubella vaccine? A CPEA Study. J. Autism Dev. Disord., 2006, 36:
299316.
Roid, G. M. and Miller, L. J. Leiter International Performance Scale
Revised: Examiners Manual. Stoelting Co., Wood Dale, IL, 1997.
Rutter, M., Le Couteur, A. and Lord, C. Autism Diagnostic Interview
Revised. Western Psychological Services, Los Angeles, CA, 2003.
Scholle, S. and Schafer, T. Atlas of states of sleep and wakefulness in
infants and children. Somnologie, 1999, 3: 163241.
Schreck, K. A. and Mulick, J. A. Parental reports of sleep problems in
children with autism. J. Autism Dev. Disord., 2000, 2: 127135.
Segawa, M. and Nomura, Y. Pathophysiology of autism: evaluation of
sleep and locomotion. In: R. Tuchman and I. Rapin (Eds) Autism. A
Neurological Disorder of Early Brain Development. Mac Keith Press,
London, 2006: 249264.
 2010 European Sleep Research Society, J. Sleep Res., 20, 338347
Sleep in autism 347
Takase, M., Taira, M. and Sasaki, H. Sleepwake rhythm of autistic
children. Psychiatry Clin. Neurosci., 1998, 52: 181182.
Terzano, M. G. and Parrino, L. Origin and signicance of the
cyclic alternating pattern (CAP). Sleep Med. Rev., 2000, 4: 101
123.
Terzano, M. G., Mancia, D., Salati, M. R., Costani, G., Decembrino,
A. and Parrino, L. The cyclic alternating pattern as a physiologic
component of normal NREM sleep. Sleep, 1985, 8: 137145.
Terzano, M. G., Parrino, L. and Spaggiari, M. C. The cyclic
alternating pattern sequences in the dynamic organization of sleep.
Electroencephalogr. Clin. Neurophysiol., 1988, 6: 437447.
Terzano, M. G., Parrino, L., Smerieri, A. et al. Atlas, rules and
recording techniques for the scoring of cyclic alternating pattern
(CAP) in human sleep. Sleep Med., 2001, 2: 537553.
Tordjman, S., Anderson, G. M., Pichard, N., Charbuy, H. and
Touitou, Y. Nocturnal excretion of 6-sulphatoxymelatonin in
children and adolescents with autistic disorders. Biol. Psychiatry,
2005, 57: 134138.
Wechsler, D. Wechsler Intelligence Scale for ChildrenIII [Italian
standardization by A. Orsini]. Organizzazioni Speciali, Firenze,
2006.
Wechsler, D. Wechsler Preschool and Primary Scale of Intelligence
[Italian standardization by C. Cianchetti Faucello]. Organizzazioni
Speciali, Firenze, 2008.
Wiggins, L., Rice, C. E. and Baio, J. Developmental regression in
children with an autism spectrum disorders identied by population-
based surveillance system. Autism, 2009, 13: 357374.
Wiggs, L. Sleep problems in children with developmental disorders. J.
Roy. Soc. Med., 2001, 94: 177179.
Williams, G. P., Sears, L. L. and Allard, A. Sleep problems in children
with autism. J. Sleep Res., 2004, 13: 265268.