Research in Autism Spectrum Disorders 7 (2013) 1595–1616

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Research in Autism Spectrum Disorders

Journal homepage: http://ees.elsevier.com/RASD/default.asp

Comorbidity in autism spectrum disorder: A literature review

Arlene Mannion, Geraldine Leader *
National University of Ireland, Galway, Ireland

A R T I C L E I N F O A B S T R A C T

Article history: Comorbidity is defined as the co-occurrence of two or more disorders in the same person
Received 10 September 2013 (Matson & Nebel-Schwalm, 2007). The current study provides a review of the literature on
Accepted 10 September 2013 comorbidity, in relation to comorbid psychiatric and medical disorders in babies and
infants, children, adults and across the lifespan. We also examine comorbid conditions
Keywords: such as attention deficit/hyperactivity disorder (AD/HD), epilepsy, gastrointestinal
Comorbidity
symptoms, sleep problems, feeding problems and toileting problems in individuals with
Autism spectrum disorder
autism spectrum disorder.
Attention deficit/hyperactivity disorder
(AD/HD) ß 2013 Elsevier Ltd. All rights reserved.
Epilepsy
Sleep problems
Gastrointestinal symptoms

Contents

1. Comorbid psychiatric and medical conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1596

1.1. Babies and infants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1596
1.2. Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1596
1.3. Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1598
1.4. Lifespan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1600
1.5. Attention deficit/hyperactivity disorder (AD/HD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1600
1.6. Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1603
1.7. Gastrointestinal symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1605
1.8. Sleep problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1608
1.9. Feeding problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1611
1.10. Toileting problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1611
2. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1613
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1613
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1613

Comorbidity is defined as the co-occurrence of two or more disorders in the same person (Matson & Nebel-Schwalm,
2007). A comorbid condition is a second order diagnosis which offers core symptoms that differ from the first disorder.
Comorbidity in the assessment of autism spectrum disorder (ASD) is a topic that has infrequently been addressed (Matson &
Nebel-Schwalm, 2007). One of the main difficulties in diagnosing comorbid psychopathology is the lack of diagnostic

* Corresponding author at: Irish Centre for Autism and Neurodevelopmental Research, School of Psychology, National University of Ireland, Galway,
Ireland. Tel.: +353 91 49 3434; fax: +353 91 521355.
E-mail address: [email protected] (G. Leader).

1750-9467/$ – see front matter ß 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.rasd.2013.09.006
1596 A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

instruments designed to screen for these disorders in individuals with ASD. Instruments are only recently being developed,
piloted and tested for reliability and validity. Instruments designed for assessing comorbid psychopathology in adults with
ASD include the Psychopathology in Autism Checklist (PAC) (Helverschou, Bakken, & Martinsen, 2009) and the Autism
Spectrum Disorders-Comorbidity for Adults (ASD-CA) (Matson, Terlonge, & González, 2006).
Instruments designed to screen for comorbid psychopathology in children are a more recent development than the
instruments designed for adults. Comorbid disorders often are more difficult to diagnose at a younger age. The Baby and
Infant Screen for Children with aUtIsm Traits (BISCUIT), Part II (Matson, Boisjoli, & Wilkins, 2007) was developed to screen for
comorbid psychopathology in infants aged 16–37 months and has been psychometrically validated (Matson, Fodstad,
Mahan, & Sevin, 2009). The Autism Spectrum Disorders Comorbidity-Child Version (ASD-CC) (Matson & González, 2007) is
another instrument used to diagnose comorbid psychopathology in children. Leyfer et al. (2006) modified the existing
instrument The Kiddie Schedule for Affective Disorders and Schizophrenia for use with children and adolescents with ASD.
The modified instrument, the Autism Comorbidity Interview-Present and Lifetime Version (ACI-PL) was used to research
prevalence rates of specific disorders.

1. Comorbid psychiatric and medical conditions

1.1. Babies and infants

While there is now a great emphasis on the early diagnosis of ASD and the provision of early intensive behavioral
intervention programs, there is a lack of research regarding comorbid conditions in very young children. The Baby and Infant
Screen for Children with aUtIsm Traits (BISCUIT), Part II (Matson et al., 2007) is an instrument developed to screen for
comorbid psychopathology, and has been used in all of the following studies. Fodstad, Rojahn, and Matson (2010) divided
participants into the ASD group and atypically developing group. They then divided participants by age groups into 12–18
months, 19–24 months, 25–31 months and 32–39 months. The authors found that those with ASD had more severe
comorbid symptoms than atypically developing toddlers. Younger children had fewer problems, and there was an increasing
trend as the older age groups displayed the most severe problems across all classes of behaviors.
Kozlowski, Matson, Belva, and Rieske (2012) compared feeding and sleeping issues using items on the BISCUIT Part II, in
children with Autistic disorder, Pervasive Developmental Disorder-Not otherwise specified (PDD-NOS) and atypically
developing children without an ASD. Children with Autistic disorder presented with significantly more feeding and sleeping
problems than children with PDD-NOS or atypically developing children. Those with PDD-NOS presented with more feeding
and sleeping issues than atypically developing children. When developmental functioning is controlled for, there was a
difference between groups in terms of feeding and sleeping issues.
Infants with autistic disorder had higher avoidance and anxiety scores than infants with PDD-NOS or atypically
developing infants (Davis et al., 2010). Davis et al. (2012) found that as communication scores increased, so did anxiety
scores in children with autistic disorder. The authors discussed the importance communication plays in terms of anxiety.
Infants and toddlers with ASD need to understand from others what they should be anxious of, and through this lack of
understanding, they may be likely to be overly anxious. The authors also commented on the likelihood that children with
lower communication ability may be unable to accurately communicate any anxiety experienced, thus appearing that they
experience lower levels of anxiety overall. Additionally, females were found to have significantly higher communication
scores.
Matson and Tureck (2012) conducted a literature review about the current status of BISCUIT-Parts 1, 2 and 3. While Part 2
is used to determine comorbid psychopathology, Part 1 is used as a diagnostic tool for ASD, and Part 3 is a measure of
challenging behavior. The article gives an overview of all the research conducted using the BISCUIT as well as research that is
currently underway, such as a 15 nation study using the BISCUIT (Table 1).

1.2. Children

Investigation of co-occurrences of medical and psychiatric conditions, such as sleep disorders, epilepsy, food intolerance,
gastrointestinal dysfunction, mood disorder, aggressive and self-injurious behaviors were examined in a study (Ming,
Brimacombe, Chaaban, Ximmerman-Bier, & Wagner, 2008). Sleep disorders were found to be associated with
gastrointestinal dysfunction and with mood disorders (Ming et al., 2008). No association was found between epilepsy
and any of the co-occurring conditions. Individuals with a pervasive developmental disorder (PDD) diagnosis were more
likely to have a medical disorder, while participants with Asperger syndrome were more likely to have psychiatric
comorbidities (Ming et al., 2008).
Hess, Matson, and Dixon (2010) used the Autism Spectrum Disorder Comorbidity-Child Version (ASD-CC) (Matson &
González, 2007) to compare symptoms in children and adolescents with and without autism spectrum disorder. Differences
lay between children and adolescents with autism spectrum disorder and typically developing children in symptoms of
worry/depressed behavior, under-eating, avoidant behavior and repetitive behavior. There was no significant difference
between the two groups in conduct and tantrum behaviors. Matson, Fodstad, and Dempsey (2009) used the under and over
eating subscale of the ASD-CC to investigate feeding difficulties among four groups; autism, pervasive developmental
 A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616
Table 1
Summary of comorbid psychopathology in babies/infants with ASD articles.

Study Research question Age of Number of Measures used Outcome

participants participants

Davis et al. (2010) To compare anxiety and avoidant behavior 17–37 months 513 Baby and Infant Scale Infants with Autistic Disorder had higher anxiety
between infants/toddlers with autistic disorder, for Children with aUtIsm and avoidant behavior scores than those with
PDD-NOS and atypically developing children Traits (BISCUIT) (Part II) PDD-NOS and atypically developing children
(Matson, Boisjoli, &
Wilkins, 2007)
Davis, Moree, et al. (2011) To determine whether deficits in communication 15–36 months 735 BISCUIT (Part II) As communication increased, so did anxiety in
skills have an effect on the expression of anxiety children with ASD compared to typically
in infants and toddlers developing children
Fodstad, Rojahn, and Matson (2010) To compare comorbid psychopathology in 12–39 months ASD: 109, Atypical BISCUIT (Part II) Those with ASD had more severe comorbid
toddlers with ASD and atypically developing controls: 160 symptoms than atypical controls, with there
children, and across age ranges being an increasing trend of comorbid symptoms
as age increased
Kozlowski, Matson, To compare feeding and sleeping difficulties 17–37 months 1747 BISCUIT (Part II) Children with Autistic disorder had more feeding
Belva, and Rieske (2012) between infants/toddlers with autistic disorder, and sleeping difficulties than children with PDD
PDD-NOS and atypically developing children NOS or atypically developing children

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disorder-not otherwise specified (PDD-NOS), atypically developing children and typically developing children. Individuals
with autism and PDD-NOS had higher rates of feeding difficulties than typically or atypically developing children.
Davis, Moree, et al. (2011) compared anxiety symptoms and communication scores among children with autistic disorder
(AD), Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) and those with no diagnosis. Anxiety
decreased as communication deficits increased for those with AD compared to those with PDD-NOS or no diagnosis. In
contrast, anxiety increased as communication deficits increased, compared to those with no diagnosis. The authors
interpreted the findings of lower anxiety scores as communication deficits increased in AD in two ways. Firstly, those with AS
may reflect a severe presentation overall across areas of functioning and a decreased ability to be anxious. Secondly,
increased communication deficits may impair children from being able to express symptoms of anxiety, as they are currently
defined in the ASD-CC.
Mannion, Leader, and Healy (2013) also used the ASD-CC to investigate comorbid psychopathology in children and
adolescents with ASD. The mean ASD-CC subscale scores were all no/minimal impairment. Mannion et al. (2013) found that
46.1% of children and adolescents had a comorbid disorder. When intellectual disability was included, this number rose to
78.7%. It was found that 15.7% of individuals presented with an anxiety disorder. The ASD-CC subscales of avoidant behavior
and under-eating were found to be significant predictors of sleep problems in those with ASD.
Joshi et al. (2010) used the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-E)
(Orvaschel, 1994; Orvaschel & Puig-Antich, 1987). Compared to an age-matched and sex-matched control group, youth with
ASD suffered from a significantly higher number of comorbid conditions than youth without ASD. Ninety five percent of
those with ASD had three or more comorbid psychiatric diagnoses, while 74% had five or more comorbid disorders. Those
with ASD had more anxiety disorders, including specific phobia and agoraphobia, than controls. Those without ASD were
more likely to have substance use disorders than those with ASD. Leyfer et al. (2006) modified the K-SADS-E to create the
Autism Comorbidity Interview-Present and Lifetime Version (ACI-PL).
Leyfer et al. (2006) found specific phobia to be the most common comorbid diagnosis among children with ASD, followed
by obsessive compulsive disorder (OCD). While 37% of children with autism had a diagnosis of OCD in Leyfer et al.’s study,
only 8% of children had a diagnosis in Simonoff et al. (2008) study. Simonoff et al. (2008) used the Child and Adolescent
Psychiatric Assessment, and found social anxiety disorder to be the most common, followed by attention deficit/
hyperactivity disorder (AD/HD), and oppositional defiant disorder (ODD). They also found that 70% of children had at least
one comorbid disorder and 41% had two or more. The presence of epilepsy was a risk factor for a psychiatric disorder.
Strang et al. (2012) used the Child Behavior Checklist to examine anxiety and depression symptoms in children with ASD.
Fifty-six percent of individuals were in the clinical range of anxiety symptoms, while 24% were in the borderline range for
depression. In contrast to previous research, higher IQ or fewer ASD symptoms did not predict anxiety and depression
symptoms in ASD. In support, Amr et al. (2012) found that children with comorbid psychiatric disorders had significantly
lower IQ than those without comorbid psychiatric disorders. Sixty-three percent of children were diagnosed with at least one
comorbid psychiatric disorder, which is supported by previous literature (Simonoff et al., 2008) (Table 2).

1.3. Adults

While a number of studies have used structured clinical interviews to diagnose psychiatric disorders in adults with ASD
(Hofvander et al., 2009; Lugnegard, Unenge Hallerback, & Gillberg, 2011; McCarthy et al., 2010), others used measures
especially designed for ASD (e.g. the Psychopathology in Autism Checklist, PAC; Helverschou et al., 2009; Autism Spectrum
Disorders-Comorbidity for Adults, ASD-CA; Matson et al., 2006), and intellectual disability (e.g. Diagnostic Assessment for
the Severely Handicapped-revised, DASH-II; Matson, 1995a).
The Autism Spectrum Disorders-Comorbidity for Adults (ASD-CA) (Matson et al., 2006) is a 37 item scale, which includes
five subscales: Anxiety/repetitive behaviors; Conduct problems; Irritability/Behavioral excesses; Attention/Hyperactivity/
Impulsivity and Depressive symptoms. The scale’s reliability was established by Matson and Boisjoli (2008). LoVullo and
Matson (2009) developed cut-off scores for the subscales of the ASD-CA. They compared the frequency of symptoms across
three groups; individuals with intellectual disability (ID), individuals with ID and ASD, and individuals with ID, ASD and
additional psychopathology.
The ID and ASD group scored significantly higher than the ID group on most subscales, except for conduct problems. It
was suspected that individuals with ID, ASD and additional psychopathology would score highest, however this was not the
case. The authors suggested that this may be due to the differences between the groups in terms of usage of psychotropic
medication. Over 71% of the ID, ASD and additional psychopathology group were on psychotropic medication, compared to
15.8% of those in the ID and ASD group. The authors commented on the overall suppressive effect on behavior that
psychotropic medication can have (LoVullo & Matson, 2009).
The Psychopathology in Autism Checklist (PAC) (Helverschou et al., 2009) is a 42 item scale, with five subscales;
Psychosis, Depression; Anxiety disorders; Obsessive Compulsive Disorder (OCD) and General Adjustment Problems.
Helverschou et al. (2009) piloted the scale, tested its reliability and found acceptable psychometric properties. It was found
that the scale discriminated between adults with autism and ID with and without psychiatric disorders, and partially
between individuals diagnosed with different psychiatric disorders.
Bakken et al. (2010) used the PAC to assess the prevalence of psychiatric disorders in individuals with intellectual
disability only and those with a combination of ID and autism. Over 53% of those with autism and ID combined had high
Table 2
Summary of comorbid psychopathology in children with ASD articles.

Study Research question Age of Number of Measures used Outcome

participants participants

Amr et al. (2012) To estimate the prevalence of comorbid 6–11 years 60 Semi-structured clinical interview for Children with ASD and comorbid
psychiatric disorders in children with ASD children and and adolescents (SCICA) psychiatric disorders were found to have
in 3 Arab countries (McConaughy & Achenbach, 1994) significantly lower IQ than those with ASD
but without comorbid psychiatric
disorders

Davis, Moree, et al. (2011) Compared anxiety scores in children with 2–14 years 99 Autism Spectrum Disorders-Comorbidity Anxiety decreased as communication
Pervasive Developmental Disorder-Not for Children (ASD-CC) (Matson & deficits increased for those with Autistic

A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

Otherwise Specified (PDD-NOS), children González, 2007). Diagnostic checklist from Disorder (AD), compared to those with
with Autistic Disorder (AD) and those with the Diagnostic and Statistical Manual-Fourth Pervasive Developmental Disorder-Not
no diagnosis Edition-Text Revision (DSM-IV-TR) Otherwise Specified (PDD-NOS), or those
(APA, 2000) and the International with no diagnosis
Classification of Diseases, Tenth Edition
(ICD-10) (World Health Organization, 1992)

Hess et al. (2010) Examining symptom endorsements in ASD group: 65; 72 Autism Spectrum Disorder Comorbidity- Differences between worry/depressed
children and adolescents with ASD 14–16 years; Child Version (ASD-CC) (Matson & behavior, under-eating, over-eating,
compared to typically developing children Control group González, 2007) avoidant behavior and repetitive behavior
and adolescents 4–14 years

Joshi et al. (2010) Compared a psychiatrically referred 3–17 years ASD group: 217; Schedule for Affective Disorders and Youth with ASD have high levels of
population with ASD to controls Control group: 217 Schizophrenia for School-Age Children psychiatric comorbidity than those
(K-SADS-E) (Orvaschel & Puig-Antich, without ASD
1987)

Leyfer et al. (2006) Piloted modified instrument, the Autism 5–17 years 109 Autism Comorbidity Interview-Present Specific phobia was the most common
Comorbidity Interview-Present and and Lifetime Version (ACI-PL) comorbid disorder
Lifetime Version (ACI-PL)

Mannion et al. (2013) Investigated frequency of comorbid 3–16 years 89 ASD-CC It was found that 46.1% of individuals had a
psychopathology, sleep problems, comorbid disorder, with this number rising
gastrointestinal symptoms and epilepsy. to 78.7% if intellectual disability is included
Also investigated predictors of sleep
problems

Matson, Fodstad, and Comparing feeding problems among with 3–16 years 279 ASD-CC Those with autism and PDD-NOS had more
Dempsey (2009) autism, PDD-NOS, atypically developing issues than atypically developing and
children and typically developing children typically developing children

Ming et al. (2008) Investigating concurrent clinical disorders 2–18 years 160 Retrospective analysis of a clinical Individuals with Asperger’s syndrome are
in ASD practice database more likely to have a psychiatric condition,
while those with PDD are more likely to
have a medical condition

Simonoff et al. (2008) Analysed risk factors of psychiatric 10–14 years 112 Child and Adolescent Psychiatric Seventy percent of children with ASD had
disorders in children with ASD Assessment at least one comorbid disorder

Strang et al. (2012) Investigating depression and anxiety 6–18 years 95 Child Behavior Checklist (CBCL) IQ and autism severity is not associated
symptoms in children with ASD with depression/anxiety symptoms

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psychiatric disorders scores and severe general adjustment problems, compared to 17.4% of the ID only group. Anxiety
symptoms were present in 64% of those who had a psychiatric disorder and autism and ID, compared to 52% in those who had
a psychiatric disorder and ID. The majority of individuals in both groups had more than one psychiatric disorder.
Bradley, Summers, Wood, and Bryson (2004) used the Diagnostic Assessment for the Severely Handicapped-revised
(DASH-II) (Matson, 1995a), and compared individuals with severe intellectual disability with and without ASD. Individuals
with ASD showed four times more psychiatric comorbidity than those without ASD. Those with ASD showed significantly
more anxiety, mood disorders, sleep disorders and organic syndromes than those without ASD. La Malfa et al. (2007) also
used the DASH-II. Participants were compared in terms of whether screened positive for a Pervasive developmental
disorders (PDD) or not, and if they were in the ‘clinical significance’ or ‘no clinical diagnosis’ groups, based on their scores on
the DASH-II. PDD was correlated with an increased presence of psychiatric disorders. A relationship was also observed
between PDD and mood, mania and depression.
Hermans, van der Pas, and Evenhuis (2011) conducted a literature review of instruments assessing anxiety in adults with
intellectual disability. Self-report measures, informant-report measures and diagnostic instruments were reviewed. The
most promising self-report instrument was the Glasgow Anxiety Scale for people with an Intellectual Disability (GAS-ID)
(Mindham & Espie, 2003), while the Anxiety, Depression and Mood Scale (ADAMS) (Methot & Morin, 2004) is the most
promising informant-report measure. Hermans et al. (2011) included the PAC in their review, and found the pilot study to be
of good methodological quality, while the anxiety subscale of the PAC had moderate reliability but did not differentiate
between different psychiatric diagnoses.
A number of studies used structured clinical interviews. Lugnegard et al. (2011) examined psychiatric comorbidity in
individuals with Asperger syndrome, and found that 70% of individuals had at least one episode of major depression, while
50% had suffered from recurrent depressive disorders. Fifty six percent of individuals had an anxiety disorder. Hofvander
et al. (2009) compared the frequency of psychiatric disorders among three groups; individuals with Autistic disorder, those
with Asperger syndrome and those with pervasive developmental disorder-not otherwise specified (PDD-NOS). Forty-three
percent of individuals were diagnosed with attention deficit/hyperactivity disorder (AD/HD). Fourteen percent had a
diagnosis of dyslexia. The most common comorbid condition was mood disorder, with 53% of individuals having a diagnosis,
followed by anxiety disorder, whereby 50% had a diagnosis. One third of individuals had been treated with an antidepressant
at least once in their lives. The frequency of comorbid diagnoses did not differ between the ASD subgroups or between males
and females.
McCarthy et al. (2010) used interviews also, but they additionally examined the association between challenging
behavior and comorbid psychopathology. They compared those with ID and ASD, and those with ID only. There were
significant differences in comorbid psychopathology between those with and without ASD. Those with ASD and challenging
behavior were not more likely to receive a psychiatric diagnosis than those with ASD without challenging behavior.
However, those with ASD and challenging behavior were less likely to receive a diagnosis of schizophrenia. The authors
suggested that the presence of challenging behavior in an individual with ASD may make the diagnosis of psychotic
symptoms more difficult. There was no association between challenging behavior when age, level of ID and gender was
controlled for. A diagnosis of ASD predicted challenging behavior, but a diagnosis of a psychiatric disorder did not.
Morgan, Roy, and Chance (2003) collected data using medical records and psychiatric case notes. Thirty-five percent of
those with autism had another comorbid psychiatric condition. The most common psychiatric diagnosis was depression,
whereby 20% had a diagnosis. Eleven percent of individuals with ASD had a diagnosis of bipolar affective disorder, while 5%
had a diagnosis of schizophrenia. Thirty four percent of individuals had a diagnosis of epilepsy, while 6% had a diagnosis of
hypothyroidism. Similar to LoVullo and Matson (2009), a high percentage (50%) of individuals were on at least one
psychotropic medication. Forty percent of those on neuroleptics did not have an additional psychiatric diagnosis.
Munesue et al. (2008) assessed individuals with ASD for mood disorders in an outpatient clinic. Thirty-six percent of
individuals were diagnosed with mood disorder. In those with mood disorders, bipolar disorder accounted for 75% of the
cases. None of the individuals with autistic disorder had mood disorders. The majority (75%) of those with mood disorders
had a diagnosis of Asperger syndrome.

1.4. Lifespan

Davis, Hess, et al. (2011) examined the developmental trajectory of anxiety symptoms across the lifespan in individuals
with ASD. The study examined anxiety in toddlers, children, young adults and older adults, using three different measures;
the BISCUIT Part 2 (Matson et al., 2007), ASD-CC (Matson & González, 2007), and the ASD-CA (Matson et al., 2006). Anxiety
rose from toddler-hood, peaked in childhood, decreased through young adulthood and began to rise again in older aged
individuals. Future research should examine how other comorbid symptoms change throughout the lifespan (Table 3).

1.5. Attention deficit/hyperactivity disorder (AD/HD)

The prevalence of Attention-deficit/hyperactivity disorder (AD/HD) in those with ASD has ranged from 14% to 78%
(Gargaro, Rinehart, Bradshaw, Tonge, & Sheppard, 2011). In a recent study, Mannion et al. (2013) found that 18% of children
and adolescents with autism spectrum disorder also had a comorbid diagnosis of AD/HD. Mannion et al. (2013) also
examined predictors of sleep problems and found that AD/HD was not a significant predictor of sleep problems in children
Table 3
Summary of comorbid psychopathology in adults with ASD and throughout the lifespan articles.

Study Research question Age of participants Number of Measures used Outcome

participants

Bakken et al. (2010) Compared psychopathology in 14–72 years 194 (62 in autism Psychopathology in Autism 53.2% of those with ASD + ID had
those with ASD, and those with group and 132 in Checklist (PAC) (Helverschou high psychiatric disorder score,
ASD and intellectual disability ID group) et al., 2009) and severe general adjustment
(ID) scores, while 17.4% of the ID only
group had high scores

Bradley et al. (2004) Comparing psychiatric and 14–20 years 12 Diagnostic Assessment for the Individuals with ASD showed 4
behavior disorders in individuals Severely Handicapped-II times as much psychiatric

A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

with severe ID with and without (DASH-II) (Matson, 1995a) comorbidity as those without
autism ASD

Davis, Hess, et al. (2011) Investigating anxiety symptoms 18–36 months 40 Baby and Infant Screen for Anxiety rose from toddler-hood,
across the lifespan in ASD Children with aUtIsm Traits peaked in childhood, decreased
(BISCUIT) (Part II) (Matson et al., through young, adulthood and
2007). Autism Spectrum rose again in older adulthood
Disorders- Comorbidity-Child
Version (ASD-CC) (Matson and
González, 2007). Autism
Spectrum Disorders-
Comorbidity for Adults (ASD-CA)
(Matson et al., 2006)
3–16 years 34
20–48 years 30
49–65 years 27

Helverschou et al. (2009) Pilot study using the 17–56 years 35 Psychopathology in Autism The scale has acceptable
Psychopathology in Autism Checklist (PAC) (Helverschou psychometric properties, and
Checklist (PAC) et al., 2009) discriminates between adults
with ASD and ID with and
without psychiatric disorders

Hofvander et al. (2009) Investigated psychiatric 16–60 years 122 Structured Clinical Interview for Lifetime psychiatric axis I
problems in individuals with DSM-IV-Axis I Disorders (SCID-I) comorbidity was very common,
ASD and normal intelligence (First, 1997) especially mood and anxiety
disorders, as well as attention
deficit/hyperactivity disorder
(AD/HD)

La Malfa et al. (2007) Compared those with No age range given 90 DASH-II Pervasive
pervasive developmental Mean age: 38.4 years developmental disorders were
disorders (PDDs) to those clearly correlated with increased
without, presence of psychiatric disorders

LoVullo and Matson (2009) 1) To calculate cut-off scores No age range given; 313 ASD-CA ID+ASD group scored higher than
for subscales of the ASD-CA Mean ID group: the ID group on most subscales,
55 years except for conduct problems
2) To compare the frequency of Mean ID + ASD group:
symptoms among 3 groups: 49 years; Mean
individuals with ID; individuals ID + ASD +
with ID + ASD and individuals psychopathology

1601
with ID, ASD and additional group: 48 years
psychopathology
 1602
Table 3 (Continued )

A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

Study Research question Age of participants Number of Measures used Outcome
participants

Lugnegard et al. (2011) Investigated psychiatric No age range 54 Structured Clinical Interview for Mood disorders and anxiety
comorbidity in young adults given. Mean age: DSM-IV Axis I Disorders (SCID-I) disorders are common in
with Asperger Syndrome 27 years (First & Gibbon, 2004) Asperger Syndrome

Matson and Boisjoli (2008) Developed ASD-CA and tested 16–78 years 169 ASD-CA The internal consistency of the
its reliability scale was good, and well above
the acceptable cut-off

McCarthy et al. (2010) Investigated the relationship 18–65 years 686 (125 with ASD + ID; International Classification of There was no association
between challenging behavior 562 with ID alone) Diseases-10 (ICD-10) clinical between comorbid psycho-
and comorbid psychopathology criteria using information pathology and challenging
in adults with ASD and ID, gathered from interviews with behavior, when level of ID,
compared to adults with ID alone key informants and the patients gender and age were controlled
for

Morgan et al. (2003) Examined the prevalence rates No age range given 164 Medical records and psychiatric Thirty-five percent of those with
of major psychiatric disorders case notes ASD had a comorbid psychiatric
in learning disabled adults with disorder
autism and analysed the use
of medication

Munesue et al. (2008) Investigated the frequency 12+ years 44 Interviewing based on Thirty-six percent of those with
of mood disorders in individuals Diagnostic and Statistical ASD had a mood disorder
with ASD Manual of Mental Disorders IV
(DSM-IV) criteria of mood
disorder
 A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616 1603

and adolescents with autism spectrum disorder. In their literature review, Gargaro et al. (2011) provided evidence of the
current status of neuroimaging research in autism and ASD. The authors also focused on the theoretical models and
neuropsychology of the two disorders as well as treatment strategies. They commented on the importance of considering the
social outcome of treatment, as children with autism and AD/HD comorbidity are at increased risk of bullying when
compared to children with either autism or AD/HD alone (Gargaro et al., 2011; Montes & Halterman, 2007).
As afore mentioned, Simonoff et al. (2008) found AD/HD to be the second most common comorbid condition in their
sample. Keen and Ward (2004) compared the prevalence of ASD and comorbidity in 1997 and 2001. In that time, there was a
significant increase in the number of children with ASD AD/HD, from 5.2% to 13.7% (Keen & Ward, 2004). Skokauskas and
Gallagher (2012) compared children with ASD to those without. The authors found that almost half (44.78%) of the ASD
group met criteria for clinically significant attention deficit/hyperactivity disorder. Borderline clinically significant
difficulties were found for the AD/HD subscale for 47% of children with ASD (Skokauskas & Gallagher, 2012).
Goldstein and Schwebach (2004) conducted a retrospective chart review study on children with a diagnosis of either
pervasive developmental disorders (PDDs) or AD/HD. It was found that 26% of those with PDDs met DSM-IV criteria for the
combined type of AD/HD, while 33% met criteria for the Inattentive type of AD/HD. Forty-one percent of those with PDDs
did not have a comorbid diagnosis of AD/HD. Those with PDDs and the combined type of AD/HD did not significantly
demonstrate more impairment in daily life functioning than those with a PDD only. However, these children with a
comorbid diagnosis were rated by parents and teachers as experiencing more daily living difficulties than those with a
PDD alone.
Mayes, Calhoun, Mayes, and Molitoris (2012) conducted a study to determine what symptoms overlap in ASD and AD/HD
and what symptoms are distinct. Mayes et al. (2012) compared children with high functioning autism, low functioning
autism, AD/HD combined type and AD/HD inattentive type. The authors also compared the scores to typically developing
children whose results had been used in a previous study. The study found that while autism is distinct from AD/HD but the
core symptoms of attention deficit, hyperactivity and impulsivity are part of autism. The authors state that autism and AD/
HD are ‘‘neurobiological disorders with similar underlying neuropsychological deficits’’ (p. 283).
Sinzig, Morsch, Bruning, Schmidt, and Lehmkuhl (2008) compared children with ASD and comorbid AD/HD symptoms to
children with ASD, but without AD/HD symptoms, and to children with AD/HD and typically developing children. They
exhibited executive functioning skills such as inhibition, flexibility, working memory and planning. Children with comorbid
AD/HD symptoms showed more problems in inhibitory performance when compared to children with ASD alone. The ASD
and comorbid AD/HD group showed similarities to the AD/HD only group with regard to inhibitory performance, but not in
working memory deficits. The study also found that individuals with ASD and comorbid AD/HD have more of a speed
problem than a comprehension problem in planning, working memory of flexibility tasks.
Nydén et al. (2010) compared adults with ASD to those with AD/HD and those with ASD and comorbid AD/HD. The
authors compared groups in terms of intellectual ability, learning and memory, attention/executive function and theory of
mind function. As supported by Mayes et al. (2012), there appeared to be an overlap between the three diagnostic categories.
There is also distinction between the three groups, as the neurocognitive problems experienced by the ASD and comorbid
AD/HD group were not just a summary of the ASD and AD/HD groups. The authors commented that children with
neuropsychiatric developmental disorders should be re-examined as adults as ‘criteria for diagnosis may not be fulfilled and
the neurocognitive functions may have changed over time’ (p. 1667) (Table 4).

1.6. Epilepsy

The prevalence of epilepsy among all children is estimated at 2–3% compared to some 30% in autism (Tuchman & Rapin,
2002). Variability in prevalence rates has been attributed to the heterogeneity of samples with respect to age, sex,
comorbidity, subtype of pervasive developmental disorder (PDD) or intellectual disability (ID) (Amiet et al., 2008). In a
retrospective review of electroencephalography (EEG) data and review of medical record charts, 40% of children referred
were diagnosed with epilepsy (Gabis, Pomeroy, & Andriola, 2005). However, this is not surprising as epilepsy symptoms
were present in many of the children, where half presented with convulsions. Mannion et al. (2013) found that 10.1% of
children and adolescents with ASD had a comorbid diagnosis of epilepsy. The authors found that epilepsy was not a
significant predictor of sleep problems in those with ASD.
Amiet et al. (2008) conducted a meta-analysis of epilepsy in autism. The authors investigated the relationships between
epilepsy and intellectual disability (ID), and epilepsy and gender in individuals with autism. It was found that 21.4% of
individuals with an intellectual disability had epilepsy, while 8% of those without an intellectual disability had epilepsy.
Epilepsy in autism was found to be associated with intellectual disability. The authors found that the more severe the
intellectual disability, the more prevalent epilepsy was. The risk for epilepsy was found to be significantly higher for females
(Amiet et al., 2008).
Bolton et al. (2011) followed up 150 participants that were diagnosed with ASD in childhood, when they were 21 years of
age. They found that 22% of individuals with ASD had epilepsy. More than half of those with epilepsy had seizures occurring
weekly or less frequently. The average age of onset of confirmed epilepsy was 13.3 years, and for the majority of participants,
seizures first began after the age of 10 years. In support of Amiet et al. (2008), Bolton et al. (2011) found that females were
significantly more likely to develop epilepsy, where 30% of female participants developed epilepsy, compared to 18% of male
participants. Males had a higher age of onset of seizures than females, and they did not differ in their level of intellectual
 1604
Table 4

A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

Summary of attention deficit/hyperactivity (AD/HD) articles.

Study Research question Age of participants Number of Measures used Outcome

participants

Goldstein and To determine if a sample of children with Mean age = 8.5 years 57 Retrospective chart review. Conners 26% of those with PDDs met criteria for
Schwebach (2004) PDDs display symptoms sufficiently related to Parent and Teacher Rating the combined type of AD/HD, while 33%
AD/HD to warrant a comorbid diagnosis of AD/ Scales-Revised, Long Version met criteria for the Inattentive type of
HD. Furthermore, do children with PDDs and (CPRS-R:L & CTRS-R:L; Conners, AD/HD
AD/HD symptoms demonstrate more 1997)
impairment in daily living activities than
those children with a PDD only
Mayes et al. (2012) To determine the degree to which core ADHD 2–16 years 847 with autism; Based on DSM-IV criteria, licenced PhD AD/HD symptoms were common in
and autistic symptoms overlap and are 158 with AD/HD psychologists made the diagnosis autism
distinct
Nydén et al. (2010) To assess which types of neuro-psychological 18+ years 161 DSM-IV criteria checklist The dysfunctions of the ASD and
deficits appear to be most commonly comorbid AD/HD group cannot be seen as
associated with ASD and AD/HD in adults. The a summary of the dysfunction found in
effect of the combination of ASD with AD/HD the ASD and ADHD groups
was also studied
Sinzig et al. (2008) To evaluate and compare executive 6-18 years. 80 Examination by an experienced child Those with ASD and omorbid AD/HD
functioning (EF) profiles in children with AD/ and adolescent psychiatrist according symptoms showed more problems in
HD and in children with ASD with and without to DSM-IV-TR criteria. inhibitory performance than those with
comorbid ADHD ASD alone
Skokauskas and To examine patterns of comorbid psychiatric ASD group: 134 (67 in Child Behavior Checklist 6-18 Almost half (44.78%) of the ASD group
Gallagher (2012) problems in children with ASD and their Mean = 12.73 years; each group) (CBCL/6-18) (Achenbach & met CBCL criteria for clinically significant
parents compared to age-matched controls Control group: Rescorla, 2001) hyperactivity disorder
and their parents Mean = 11.85 years
.
 A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616 1605

disability or verbal abilities. Epilepsy was significantly more common in those with a lower overall language ability, where
45% of those with epilepsy had a very limited language ability, compared to 25% of those without epilepsy.
Turk et al. (2009) compared children with ASD who had epilepsy, with those who did not have a diagnosis of epilepsy. A
diagnosis of ASD and epilepsy was found to be associated with a later age at diagnosis of autism. The authors suggest that
either ASD develops later or diagnostic overshadowing occurred. Having ASD and epilepsy was found to be associated with
greater numbers and severities of gross and fine motor problems, incontinence, social impairments and challenging
behaviors. Those with ASD and epilepsy showed delayed daily living skills. Those with ASD and epilepsy engaged in staring
behavior, where they were found to stare longer and harder than those with ASD only. The ASD only group displayed more
brief glances as a means of eye contact and experienced more abnormal fascination with objects than the ASD and epilepsy
group.
Seizures are more frequent when intellectual disability is associated with ASD and when neurological signs are evident
(Canitano, 2007). Individuals with autism and additional neurological impairment, such as cerebral palsy are at a higher risk
for seizures (Steffenburg, Steffenburg, & Gillberg, 2003). A much lower rate of epilepsy, of approximately 6% has been
reported in children with autism without additional neurological disorders (Pavone et al., 2004). Tuchman, Rapin, and
Shinnar (1991) also found that type of language dysfunction was a risk factor for seizures, with the highest percentage of
seizures occurring in children with the most severe deficits in receptive language. DeLong and Heinz (1997) and Rapin,
Mattis, Rowan, and Golden (1977) hypothesised that the association of severe receptive language disorders with epilepsy
and with autism implicates temporal-lobe dysfunction (Tuchman & Rapin, 2002).
Matson, Neal, Hess, Mahan, and Fodstad (2010) investigated adaptive behavior, personal-social behavior, communica-
tion, motor and cognitive skills in toddlers who were atypically developing compared to those with ASD, and also compared
those with and without seizures. Toddlers with seizure disorders exhibited greater impairments across all domains of
functioning when compared to those without seizure disorders. While there was not a significant interaction found between
diagnostic group, the general trend showed that those with ASD and seizures exhibited the greatest impairments, followed
by those with ASD alone, atypically developing children without seizures and finally, atypically developing children without
seizures.
As with many other comorbid disorders, there is a lack of research in the area of adults with autism and comorbid
epilepsy. Smith and Matson (2010a, 2010b, 2010c) focused on adults with epilepsy and the relationships between epilepsy,
challenging behavior, comorbid psychopathology and social skills in three papers. In all three papers, the authors compared
four groups: (1) intellectual disability, (2) epilepsy, (3) ASD and (4) ASD and epilepsy combined. The first, Smith and Matson
(2010a) investigated challenging behavior. It was found that those with comorbid ASD and epilepsy were more impaired
than the other groups. Specifically, those with epilepsy and ID showed significantly higher disruptive behavior scores than
those with ID only group, ASD only group and epilepsy only group.
The second, Smith and Matson (2010b) investigated comorbid psychopathology, Smith and Matson (2010b) compared
ASD-CA scores among four groups; those with ID alone, those with epilepsy alone, those with ASD alone and those with ASD
and epilepsy combined. Those with ASD and a comorbid condition (e.g. epilepsy) were more impaired in terms of
psychopathology than those with ID, epilepsy or ASD on its own. The ASD and epilepsy group showed higher scores on
irritability/behavioral excesses, attention/hyperactivity and depressive symptoms than the ID alone group. Those with
combined ASD and epilepsy scored higher on the anxiety/repetitive behavior subscale and on the attention/hyperactivity
subscale than those with epilepsy alone.
The third, Smith and Matson (2010c) investigated social skills deficits. Individuals with ID and comorbid ASD and epilepsy
were significantly more impaired in social skills than those with ID alone, or those with ASD or epilepsy. Having multiple
disorders increased the odds of having diminished social skills. For the positive verbal subscale of the Matson Evaluation of
Social Skills for Individuals with sEvere Retardation (MESSIER; Matson, 1995b) individuals with ASD and epilepsy combined
were more impaired but epilepsy contributed more to the effect than ASD alone.
Matson and Neal (2009) conducted a literature review about seizures and epilepsy in ASD. The authors examined the
prevalence, nosology and etiology. They also looked at the relationship between seizures and epilepsy and regression in ASD.
The authors noted that much of the research on regression and epilepsy is correlational and that a causal link between the
two has yet to be established. They also commented on the need for clinicians to be aware of the high co-occurrence between
seizures and ASD during assessment and intervention (Table 5).

1.7. Gastrointestinal symptoms

The published literature is inconsistent regarding the prevalence of gastrointestinal problems in individuals with ASD
(Wang, Tancredi, & Thomas, 2011). The reported prevalence of gastrointestinal problems in children with ASD has ranged
from 9% to 91% (Black, Kaye & Jick, 2002; Coury et al., 2012; Fombonne & Chakrabarti, 2001; Horvath & Perman, 2002;
Ibrahim, Voigt, Katusic, Weaver, & Barbaresi, 2009; Ming et al., 2008; Molloy & Manning-Courtney, 2003; Mouridsen, Rich,
& Isager, 2010; Nikolov et al., 2009; Parracho, Bingham, Gibson, & McCartney, 2005; Smith, Farnworth, Wright, & Allgar,
2009; Taylor et al., 2002; Valicenti-McDermott, McVicar, Cohen, Wershil, & Shinnar, 2008; Wang, Tancredi, & Thomas,
2011). It has been questioned if gastrointestinal symptoms are more common in those with autism spectrum disorder
than in the general population. Kuddo and Nelson (2003) commented on the lack of research using appropriate controls in
their review.
 1606
Table 5
Summary of epilepsy articles.

Study Research question Age of participants Number of Measures used Outcome

participants

Amiet et al. (2008) To compare the prevalence of epilepsy 1–28 years 2112 Meta-analysis study so variety of Epilepsy in autism is associated with
in (1) those with and without measures used in individual studies intellectual disability and gender

A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

intellectual disability, and (2) males
and females with autism
Bolton et al. (2011) To under-take a long-term follow-up 26–56 years 150 Clinical records. Semi-structured Epilepsy was associated with gender
study of individuals with autism in interview. Where possible, the authors (female), Intellectual disability and
order to better characterise the features sought reports of electro- cephalogram poorer verbal abilities
and correlate of epilepsy in individuals (EEG) investigations that had taken
with autism place
Gabis et al. (2005) To address the incidence and 1–14 years 56 Retrospective review of EEG data and Forty percent of children with autism
electroencephalographic abnormalities Independent review of medical record were diagnosed with epilepsy
in children with pervasive charts
developmental disorders (PDDs)
Matson et al. (2010) To examine the effect that seizure 18–24 months 36 (9 in Diagnoses of seizure disorders were Those with seizures tended to be more
disorder has on symptom presentation each group) previously determined by the impaired than those without
in toddlers with ASD compared to children’s primary care physical
atypically developing children
Turk et al. (2009) To compare developmental and 7–17 years 120 (60 in Epilepsy was previously diagnosed by a Those with ASD and epilepsy showed
psychological functioning in two each group) medical professional more Motor difficulties, developmental
groups of children with ASD, one with delays and challenging behaviors than
epilepsy and one without those with ASD alone
Smith and Compared behavior problem among 4 29–72 years 100 (25 in International League Against Epilepsy Those with ASD and a comorbid
Matson (2010a) groups: Group (1) ID, Group (2) each group) (ILAE). Clinical description of seizure condition (e.g. epilepsy) were more
Epilepsy; Group (3) ASD; Group 4) activity. Available medical information impaired than those with ID, ASD or
ASD + epilepsy (e.g. family history, age of onset, prior epilepsy
neurological trauma)
Smith and Compared psychopathology scores 29–72 years 100 (25 in International League Against Epilepsy Those with ASD and a comorbid
Matson (2010b) among 4 groups: Group (1) ID; Group each group) (ILAE). Clinical description of seizure condition (e.g. epilepsy) were more
(2) Epilepsy; Group (3) ASD; Group (4) activity. Available medical information impaired than those with ID, ASD or
ASD + epilepsy (e.g. family history, age of onset, prior epilepsy
neurological trauma)
Smith and Compared social skills scores among 4 29–72 years 100 (25 in International League Against Epilepsy Those with ASD and a comorbid
Matson (2010c) groups: Group (1) ID; Group (2) each group) (ILAE). Clinical description of seizure condition (e.g. epilepsy) were more
Epilepsy; Group (3) ASD; Group 4) activity. Available medical information impaired in social skills than those with
ASD + epilepsy (e.g. family history, age of onset, prior ID, ASD or epilepsy
neurological trauma)
 A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616 1607

Ibrahim et al. (2009) compared children with autism and gastrointestinal symptoms to matched control participants. No
significant association found between autism and gastrointestinal symptoms. However, significant differences were found
between those with autism and control participants in relation to constipation and feeding issues/food selectivity. Children
with autism had a higher incidence of constipation and feeding issues. The authors suggested that these issues may have a
behavioral etiology. Insistence on sameness in children with autism may lead them to demand stereotyped diets, which may
result in an adequate intake of fibre, which in turn can lead to constipation (Ibrahim et al., 2009). Use of psychotropic
medication may also lead to feeding issues, as side-effects of medications may include appetite suppression or increased
appetite (Ibrahim et al., 2009).
Black et al. (2002) found that only 9% of children with autism had gastrointestinal symptoms prior to diagnosis,
similar to controls. Wang et al. (2011) compared gastrointestinal symptoms in children with autism to their typically
developing siblings. It was found that there were significantly more gastrointestinal symptoms in children with ASD
(42%) compared to their typically developing siblings (12%). The two most common gastrointestinal problems in
children with ASD were constipation and chronic diarrhea. The researchers divided autism severity into three groups;
Full Autism, Almost Autism and Spectrum. Increased autism symptom severity was associated with higher odds of
gastrointestinal problems (Wang et al., 2011). In contrast, Molloy and Manning-Courtney (2003) found that frequency of
gastrointestinal symptoms did not vary by age, gender, race or severity of autism. In support of this, Nikolov et al. (2009)
also found that those with gastrointestinal problems were no different from those without gastrointestinal problems in
autism symptom severity, demographic characteristics or measures of adaptive functioning. Nikolov et al. (2009) found
that when compared to children without gastrointestinal problems, those with gastrointestinal problems showed
greater symptom severity on measures of irritability, anxiety and social withdrawal. With regards to irritability, those
with current gastrointestinal symptoms had lower irritability scores than those with a history of gastrointestinal
symptoms.
Similar to the lack of instruments available for measuring comorbid psychopathology in individuals with ASD, there is an
absence of instruments to measure gastrointestinal symptoms in those with ASD. Molloy and Manning-Courtney (2003)
used medical record reviews to determine if participants in their study had gastrointestinal symptoms. Nikolov et al. (2009)
similarly reviewed medical records, as well as using a Side Effects Review Form (Research Units of Pediatric
Psychopharmacology, RUPP). Valicenti-McDermott et al. (2008) derived The Gastrointestinal Questionnaire from an
existing questionnaire, designed for typically developing children. The Autism Treatment Network developed the
Gastrointestinal Symptom Inventory (Autism Treatment Network, 2005), which is a parental-report questionnaire.
Mazurek et al. (2013) used the Gastrointestinal Symptom Inventory (Autism Treatment Network, 2005) to study the
relationships between chronic GI symptoms, anxiety and sensory over-responsivity. There was a strong association between
anxiety and sensory over-responsivity, with higher levels of anxiety among children who have greater levels of reactivity to
various sensory stimuli. Children with chronic GI symptoms evidenced higher levels of both anxiety and sensory over-
responsivity. Increasing numbers of chronic GI symptoms were associated with higher levels of anxiety and sensory over-
responsivity.
Mannion et al. (2013) also used the Gastrointestinal Symptom Inventory (Autism Treatment Network, 2005) to determine
the frequency of GI symptoms in children and adolescents with ASD. The authors found that 79.3% of individuals had at least
one gastrointestinal symptom within the last 3 months. The most common gastrointestinal symptom was abdominal pain,
where 51.7% of individuals presented with it, followed by constipation where 49.4% presented with the symptom. Total
number of GI symptoms was found to be a significant predictor of sleep problems. Specifically, abdominal pain predicted
sleep anxiety.
The Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version (QPGS-RIII) is an adaptation and
abbreviation of the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS) (Walker, Caplan-Dover, & Rasquin-Weber,
2000). The 71 item parental-report questionnaire assesses symptom criteria for pediatric functional gastrointestinal
disorders and additional gastrointestinal symptoms. Gorrindo et al. (2012) used the QPGS-RIII as well as clinical evaluations
by pediatric gastroenterologists. Agreement between parental-report gastrointestinal symptoms and physician diagnosis
was high (92.1%). The study divided participants into three groups; those with ASD and gastrointestinal symptoms, those
with ASD and no gastrointestinal symptoms and those with gastrointestinal symptoms only. Gastrointestinal symptoms in
ASD were not associated with diet or medication usage. Constipation was the most common gastrointestinal symptom, with
85% of those with ASD and gastrointestinal symptoms presenting with it. Odds of constipation were associated with younger
age, increased social impairment and lack of expressive language.
Valicenti-McDermott et al. (2008) investigated the relationship between gastrointestinal symptoms and language
regression. It was found that 68% of children with ASD were reported to have one or more lifetime gastrointestinal
symptoms. Children with language regression had more gastrointestinal problems (84%) than those without language
regression (61%). An association was observed between children with language regression, a family history of autoimmune
disease and gastrointestinal symptoms. Molloy and Manning-Courtney (2003) found that a history of regression was present
in 23.4% of children with ASD. In contrast to Valicenti-McDermott et al. (2008), Molloy and Manning-Courtney (2003) found
that regression was not significantly associated with gastrointestinal symptoms. Hansen et al. (2008) used two definitions of
regression: (1) loss of both language and social skills, and (2) loss of either language or social skills. No significant differences
were found between the children with or without regression in terms of gastrointestinal symptoms, history of seizures or
sleep problems.
1608 A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

Buie, Fuchs III, et al. (2010) published an article which provides guidelines for evaluation and treatment of common
gastrointestinal problems for health care practitioners. As many practitioners may not be aware of the high co-occurrence of
GI symptoms in those with ASD, this is an extremely important article for health care practitioners. Buie, Campbell, et al.
(2010) conducted a literature review of gastrointestinal symptoms in ASD, and provided a list of consensus statements,
including a key statement: ‘Individuals with ASDs who present with gastrointestinal symptoms warrant a thorough
evaluation, as would be undertaken for individuals without ASDs who have the same symptoms and signs’. The authors also
included a table of vocal and motor behaviors and changes in overall state. Vocal and motor behaviors that may be markers of
abdominal pain or discomfort in individuals with ASD include behaviors like frequent clearing of throat and facial grimacing.
Changes in overall state may include sleep disturbances, increased irritability and non-compliance with demands. The
authors recommend that a functional behavior assessment would be useful in interpreting these behaviors. The article also
includes a concise table of key take-away messages. One of the messages is that the communication impairments
characteristic of ASD may lead to unusual presentations of gastrointestinal disorders including sleep disturbances and
problem behaviors (Table 6).

1.8. Sleep problems

Johnson (1996) reported that 34% to 80% of children with an intellectual disability (ID) have a sleep problem (Richdale,
Francis, Gavidia-Payne, & Cotton, 2000). Rzepecka, McKenzie, McClure, and Murphy (2011) found that 77.2% of children with
ASD had sleep problems. They investigated the relationship between sleep problems, anxiety and challenging behavior.
Medication usage, sleep problems and anxiety accounted for 42% of the variance in challenging behavior, with sleep
problems being the strongest predictor. It can also be noted that children on medication scored higher on sleep problems,
anxiety and challenging behavior.
Mannion et al. (2013) found that 80.9% of children and adolescents with ASD presented with sleep problems. The
study also investigated predictors of sleep problems. Total number of gastrointestinal symptoms predicted sleep, as did
the ASD-CC subscales of under-eating and avoidant behavior. The types of sleep problems predicted by these variables
were sleep anxiety, parasomnias and daytime sleepiness. Specifically, abdominal pain predicted sleep anxiety.
Many studies have investigated the relationship between sleep and problem behavior. Goldman et al. (2011)
compared children with ASD who were good sleepers to poor sleepers. It was found that poor sleepers had a higher
percentage of behavioral problems than good sleepers. Over 75% of poor sleepers had problems with attention span and
social interactions. Poor sleepers displayed more stereotypy, hyperactivity and anxiety, as well as having more sensory
and eating issues. A poor sleeper had a high risk of exhibiting self-injurious behavior, even when age was adjusted for. A
poor sleeper had a 20.4% higher likelihood of self-injurious behavior than a good sleeper. Younger children who
were poor sleepers were more likely to have language problems, aggression, hyperactivity and poor eating habits than
older poor sleepers.
Mayes and Calhoun (2009) found that sleep problems were not related to age, IQ, gender, race, parent occupation,
neuropsychological functioning and learning ability. Sleep problems increased with severity of autistic symptoms and with
severity of parent reported symptoms, such as oppositional behavior, aggression, explosiveness, attention deficit,
impulsivity, hyperactivity, anxiety, depression and mood variability. Autism severity was the single most powerful predictor
of sleep problems and explained 20% of the variance. The most powerful combined predictors of sleep disturbances were
autism severity, hyperactivity, mood variability and aggression, explaining 31% of the variance.
Children in the pervasive developmental disorders (PDDs) group are more likely to fall asleep later at night, have longer
sleep latencies, sleep less at night, and spend a significant period of time awake during the night, when compared to controls
(Patzold, Richdale, & Tonge, 1998). Children in the PDD group displayed significantly more energetic and more difficult
daytime behavior, compared to a control group (Patzold et al., 1998). Richdale et al. (2000) used a control group in their study
of children with intellectual disability (ID), where 13% of those with an ID had a diagnosis of autism also. Sleep problems
were associated with both the intensity and frequency of family stress, and the presence of problem behavior (Richdale et al.,
2000). Children with intellectual disability and severe sleep problems showed more severe levels of daytime problem
behavior, such as aggression, non-compliance and hyperactivity (Didden, Korzilius, van Aperlo, van Overloop, & de Vries,
2002). In a single-subject study, sleep deprivation was found to increase escape-maintained self-injurious behavior in a child
with intellectual disability (O’Reilly & Lancioni, 2000).
Research has compared sleep problems in children with ASD, attention deficit/hyperactivity disorder (AD/HD),
epilepsy and typically developing children (Tsai et al., 2012). While children with ASD and AD/HD exhibited more sleep
problems than children with epilepsy, current or lifetime sleep problems did not differ between children with ASD and
children with AD/HD, or between children with epilepsy and typically developing children (Tsai et al., 2012). Schreck,
Mulick, and Smith (2004) conducted a study where information was retrieved from a database of parent reported sleep
problems; therefore all participants had sleep problems. Fewer hours of sleep per night predicted overall autism
severity scores and social skills deficits, while stereotypic behavior was predicted by fewer hours of sleep per night and
screaming during the night. Increased sensitivity to environmental stimuli in the bedroom and screaming at night
predicted communication problems. Therefore, it if of extreme importance to identify and treat sleep problems, as they
may influence the effectiveness of daily interventions (Schreck, Mulick, et al., 2004; Schreck, Williams, et al., 2004)
(Table 7).
Table 6
Summary of gastrointestinal symptom (GI) articles.

Study Research question Age of Number of Measures used Outcome

participants participants

Gorrindo et al. (2012) Compared 3 groups; ASD+GI 5–17 years 121 Clinical evaluative by pediatric Constipation was the most common GI

A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

symptoms, ASD + no GI symptoms and gastroenterologists. symptom in ASD. It was associated with
GI symptoms only Questionnaire on Pediatric younger age, increased social impairment
Gastrointestinal Symptoms- and lack of expressive language
Rome III Version (QPGS) (Walker
et al., 2000)
Hansen et al. (2008) Examined the prevalence of regressive 2–5 years 333 CHARGE Gastrointestinal history No statistically significant differences were
autism and associated demographic, form. CHARGE Sleep history found. Between children with/without
medical and developmental factors form regression in terms of gastrointestinal
symptoms, history of seizures or sleep
problems
Ibrahim et al. (2009) Compared children with ASD and GI Up to 18 years. 363 (121 case Medical records. No significant association found between
symptoms to matched control participants and ASD and GI symptoms, except more
participants 2 controls per case children with ASD had constipation and
participant) feeding issues
Mazurek et al. (2013) Investigating the relationship between 2–17 years 2973 GI symptom inventory Children with each type of GI symptom
gastrointestinal symptoms, anxiety and questionnaire (Autism had significantly higher rates of anxiety
sensory over-responsivity Treatment Network, 2005) and sensory over-responsivity
Molloy and Investigated the prevalence of GI 24–96 months 137 Medical records Twenty-four percent of children had a
Manning-Courtney (2003) symptoms in children with ASD history of at least one GI symptom. No
association was found between GI
symptoms and developmental regression
Nikolov et al. (2009) Evaluated GI symptoms in children 5–17 years 172 Medical history. Side Effects Those with GI symptoms were no different
with pervasive developmental Review Form (Research Units of from those without GI symptoms in terms
disorders (PDDs) Pediatric Psychopharmacology) of adaptive functioning or autism
symptom severity. Those with GI
symptoms showed greater irritability,
anxiety and social withdrawal, and were
less likely to respond to treatment
Valicenti-McDermott Investigated GI symptoms and 1–18 years 100 The Gastrointestinal Interview Children with language regression had
et al. (2008) language regression more GI problems than those without
language regression
Wang et al. (2011) Compared children with ASD to their 1–18 years 752 (589 participants Structured medical history More GI symptoms in children with ASD
siblings in relation to GI symptoms with ASD and 163 of interview than their typically developing siblings.
their siblings in Increased autism symptom severity was
control group) associated with higher odds of GI problem

1609
 1610
Table 7
Summary of sleep problems articles.

Study Research question Age of Number of Measures used Outcome

participants participants

A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

Goldman et al. (2011) Investigated the relationship between 2–18 years 1784 Children’s Sleep Habits Questionnaire Poor sleepers had a higher percentage of
sleep problems and problem behavior (CSHQ) (Owens, Nobile, McGuinn, & behavioral problem than good sleepers
in children with ASD Spirito, 2000). Parental Concerns
Questionnaire (PCQ) (McGrew et al.,
2007)

Mayes and Investigated variables related to sleep 1–15 years 477 Pediatric Behavior Scale (PBS) (Chervin, The strongest predictors of sleep
Calhoun (2009) problem in children with ASD Hedger, Dillon, & Pituch, 2000) disturbance were autism severity,
hyperactivity, mood variability and
aggression

Patzold et al. (1998) Explored the relationship between 3–14 years 67 (31 children Sleep Diary Children with ASD are likely to fall asleep
sleep problems and daytime behavior with ASD and 36 later, have longer sleep latencies, sleep less
participants in control at night and spend a significant period of
group) time awake during the night, when
compared to controls. Those with ASD
displayed significantly more difficult
daytime behavior than controls

Richdale et al. (2000) Examined stress, challenging behavior 2–19 years 77 (52 with ID, 7 of Sleep Problems Questionnaire Sleep problem were significantly
and sleep problem in children with which had ASD and (Richdale, Cotton, & Hibbit, 1999). associated with intensity and frequency of
intellectual disability (ID) 25 in control group) Epworth Sleepiness Scale (ESS) (Johns, parental stress and the presence of
1991). Apnoea and narcolepsy scales problem behavior
(Douglass et al., 1994)

Rzepecka et al. (2011) Investigated the relationship between 5–18 years 187 Children ‘s Sleep Habits Questionnaire Medication, sleep problems and anxiety
sleep, anxiety and challenging behavior (CSHQ) accounted for 42% of the variance in
in children with intellectual disability challenging behavior
and/or ASD

Schreck, Mulick, Investigated the relationship between 5–12 years 55 Behavior Evaluation of Disorders of Fewer hours of sleep per night predicted
et al. (2004) sleep problem and symptoms of autism Sleep (BEDS) (Schreck, 1997/1998; overall autism severity scores and social
Schreck, Mulick, & Rojahn, 2003) skills deficits

Tsai et al. (2012) Compared sleep problems in those with 6–17 years 256 Sleep Habits Questionnaire (SHQ) (Gau, There was an increased risk of sleep
ASD, AD/HD and epilepsy 2006) problems in children with ASD and AD/HD
than typically developing children
 A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616 1611

1.9. Feeding problems

Children with autism were found to have significantly more feeding problems and eat a significantly narrower range of
foods than children without autism (Schreck, Williams, & Smith, 2004). Matson and Kuhn (2001) developed the Screening
Tool of fEeding Problems (STEP) to identify feeding problems in adults with an intellectual disability. Fodstad and Matson
(2008) compared feeding problems in those with intellectual disabilities with and without autism. Individuals with ASD and
intellectual disability displayed more behaviorally-based feeding issues like food selectivity and refusal related behaviors
than those with intellectual disability alone. The ASD and intellectual disability group had more severe feeding and mealtime
problems than the intellectual disability alone group (Fodstad & Matson, 2008).
Seiverling, Hendy, and Williams (2011) modified the STEP for use with children, calling it the STEP-CHILD. The authors
then compared children with autism to children with special needs and to children with no special needs. Stealing food was
more common in children with autism than those with and without special needs. Emond, Emmett, Steer, and Golding
(2010) conducted a longitudinal study on feeding symptoms in children with ASD. Children with ASD demonstrated feeding
difficulties from infancy and had a less varied diet at 15 months of age than controls. However, energy intake or growth was
not impaired. The infants with ASD were described as ‘slow feeders’ at 6 months old. The authors suggested that effective
behavioral strategies need to address the neophobia and sensory sensitivities, e.g. colour, taste, texture, for children with
ASD.
Bandini et al. (2010) compared food selectivity between children with ASD and typically developing children. Children
with ASD exhibited more food refusal and had a more limited food repertoire than typically developing children. Sharp,
Jaquess, and Lukens (2013) completed a multi-method assessment battery involving standardized mealtime observation, a
food preference inventory and the Brief Autism Mealtime Behavior Inventory (BAMBI) (Lukens & Linscheid, 2008). Food
selectivity on the BAMBI were negatively associated with a child’s acceptance of bites and positively associated with
disruptions during the presentation of foods during a structured mealtime observation. There was no relationship between
ASD symptom severity and feeding problems. Neither was there a relationship between growth parameters and feeding
problems.
Nadon, Ehrmann Feldman, Dunn, and Gisel (2011) examined the relationship between sensory processing problems and
the number of eating problems in children with ASD, and found there was an association between both. A significant
association was found between visual and auditory sensitivity and the number of eating problems in children with ASD. The
relationship between sensory processing and feeding problems needs to be further examined in the future. For practitioners
interested in the treatment of feeding disorders, Matson and Fodstad (2009) conducted an excellent review of the treatment
of food selectivity and other feeding problems in children with ASD (Table 8).

1.10. Toileting problems

Toileting is a critical skill necessary for independent living, and incontinence is a significant quality of life barrier for
individuals with autism (Kroeger & Sorensen-Burnworth, 2009). Kroeger and Sorensen-Burnworth (2009) conducted a very
thorough literature review about toilet training individuals with autism and other developmental disabilities. They
examined teaching strategies such as graduated guidance, reinforcement-based training, scheduled sittings, elimination
schedules, punishment procedures, hydration, manipulation of stimulus control, night time training for diurnal continence
and priming and video modelling.
Dalrymple and Ruble (1992) found that lower cognition and lower verbal levels were significantly correlated with age of
accomplishment of bowel and urine training in individuals with autism. In their survey of toileting issues, the authors found
that twenty-two percent of individuals still wet at night time, with their ages ranging from nine to 32 years. Five percent of
the sample with a mean age of 23.8 years were not trained for urine, bowel or during the night. About 30% of the individuals
with autism had fears associated with toileting, whereby verbal individuals had the most. The most common toileting
problems were urinating in places other than the toilet, constipation, stuffing up toilets, continually flushing and smearing
feces.
Matson, Dempsey, and Fodstad (2010) developed the Profile of Toileting Issues (POTI) questionnaire for individuals with
an intellectual disability between the ages of 4 through adulthood. Matson, Neal, Hess, and Kozlowski (2011) examined the
reliability of the POTI and found it have good internal consistency (a = .83). Belva, Matson, Barker, Shoemaker, and Mahan
(2011) used the POTI questionnaire to investigate toileting issues in individuals with intellectual disability, ranging from 23
to 72 years. They found that lower adaptive functioning was associated with greater toileting problems. Matson, Horovitz,
and Sipes (2011) used the POTI questionnaire in 153 adults with intellectual disability, and found that the most frequently
endorsed problems were toileting accidents during the day and night. Significant differences on total POTI score were found
based on verbal ability, ambulatory ability, fiber or laxative use and level of intellectual disability. Therefore, those who were
non-verbal, non-ambulatory, using fiber or laxatives and with a profound intellectual disability had higher total scores on
the POTI.
Matson and LoVullo (2009) conducted a literature review on encopresis, soiling and constipation in children and adults
with developmental disabilities. The authors note that etiology, prevalence, assessment and treatment of encopresis, soiling
and constipation have received very little attention, and suggest that future attention and efforts by researchers are
warranted. There is a lack of research on toileting problems in developmental disabilities, and this is especially true in the
 1612
Table 8
Summary of feeding problems articles.

Study Research question Age of Number of Measures used Outcome

participants participants

Bandini et al. (2010) To compare food selectivity in children 3–11 years 111 Modified version of Youth/Adolescent Children with ASD exhibited more food

A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616

with ASD and typically developing Food Frequency Questionnaire (YAQ) refusal and had a more limited food
children (Field et al., 1999) repertoire than typically developing
children

Emond et al. (2010) To investigate the feeding, diet and 6–54 months 86 Questionnaires designed by the Avon ASD children showed feeding
growth of young children with ASD Longitudinal Study of Parents and symptoms from infancy and had a
Children (ALSPAC). See http:// spectrum disorder less varied at 15
www.bristol.ac.uk/alspc/ months, but energy intake and growth
were not impaired

Fodstad and Matson (2008) To compare feeding and mealtime 18–69 years 60 Screening Tool of feeding Problems Those with ASD + ID displayed more
problems in adults with intellectual (STEP) (Matson & Kuhn, 2001) behaviorally-based feeding problems,
disabilities with and without autism such as food selectivity and refusal
related difficulties compared to those
with ID alone

Nadon et al. (2011) To examine the relationship between 3–10 years 95 Eating Profiles (Nadon, 2007) Sensory processing problems were
sensory processing problems and the significantly related to an increase in
number of eating problems in children the number of eating problems
with ASD

Schreck, Williams, To compare eating behavior in children 7–9.5 years 436 Children’s Eating Behavior Inventory Children with autism have significantly
et al. (2004) with and without autism (CEBI) (Archer, Rosenbaum, & Steiner, more feeding problem and eat a
1991) narrower range of foods than children
without autism

Seiverling et al. (2011) To examine psychometric qualities of 2–18 years 142 STEP-CHILD (Matson & Kuhn, 2001; Stealing food was more common in
the STEP-CHILD Seiverling et al., 2011) children with autism

Sharp et al. (2013) To assess feeding problem using multi- 3–8 years 30 Food Preference Inventory Brief Autism Increased food selectivity was
method assessment Mealtime Behavior Inventory (BAMBI) Positively correlated with problem
(Lukens & Linscheid, 2008). behaviors during the observation, while
Standardized Mealtime Observation ASD Symptom severity and growth
parameters were unrelated to feeding
data
 A. Mannion, G. Leader / Research in Autism Spectrum Disorders 7 (2013) 1595–1616 1613

Table 9
Summary of toileting problems articles.

Study Research question Age of Number of Measures used Outcome

participants participants

Dalrymple and To examine age of toilet 9–38 years 100 Survey of Toilet Habits Lower cognitive level,
Ruble (1992). training, toilet training (STH) (Dalrymple & being non-verbal and
methods, and toileting Ruble, 1992) needing continued help
skills and behaviors in with toileting was
individuals with autism associated with age of
accomplishing toilet
training

case of autism spectrum disorders. Much more research is needed to examine the prevalence of toileting problems in
individuals with ASD, and to investigate other variables that may be associated with toileting problems, such as
communication and challenging behavior (Table 9).

2. Conclusion

It is important that there is an understanding of the types of comorbid disorders that affect those with ASD among both
practitioners and researchers. In order to implement the most effective intervention plans for those with ASD, comorbid
conditions should be considered. Comorbidity in ASD is an area where much more research is required.

Acknowledgement

This research was conducted by the first author under the supervision of the second author in partial fulfillment of the
requirements for her Ph.D. degree in ABA at NUI, Galway.

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