Open Journal of Psychiatry, 2013, 3, 329-334 OJPsych
http://dx.doi.org/10.4236/ojpsych.2013.33034 Published Online July 2013 (http://www.scirp.org/journal/ojpsych/)
Clinical and therapeutic implications of psychiatric
comorbidity in high functioning autism/Asperger
syndrome: An Italian study
Silvia Giovinazzo1, Sara Marciano1, Graz ia Giana2, Paolo Curatolo1, Maria-Cristina Porfirio1
1Department of Child Neurology and Psychiatry, Tor Vergata University, Rome, Italy
2Department of Neuroscience, Child and Adolescence Psychiatry Unit, Children Hospital Bambino Gesù, Rome, Italy
Received 10 March 2013; revised 12 April 2013; accepted 20 April 2013
Copyright © 2013 Silvia Giovinazzo et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The present study describes the occurrence of psychi-
atric comorbid disorders in a cohort of 86 high func-
tioning autism (HFA)/Asperger syndrome (AS) pa-
tients, examined at Child Neurology and Psychiatry
Unit of Tor Vergata University. 38 patients out of 86
(44.2%) presented one or more psychiatric comorbid-
ities, such as mood disorders, Attention Deficit/Hy-
peractivity Disorder (ADHD), Tourette syndrome
(TS), anxiety disorders, including obsessive-compul-
sive disorder (OCD), and psychotic symptoms. We
compared our sample with the evidences from the
scientific literature on psychiatric comorbidity in
ASD patient, in particular in HFA/AS. In this paper
we focu s on the high frequency of comorbid psy chiat-
ric disorders in HFA/AS patients, such as mood dis-
orders, Attention Deficit/Hyperactivity Disorder
(ADHD), Tourette syndrome (TS), anxiety disorders,
including obsessive-compulsive disorder (OCD), and
psychosis, including schizophrenia. We analyzed rates
of all psichiatric comorbidities diagnosed in a sample
of HFA/AS subjects and we compared findings from
our study with the evidences from the scientific lit-
erature on psychiatric comorbidity in ASD patients,
in particular HFA/AS. We point out that comorbid
psychiatric symptoms can be hardly diagnosed, be-
cause they could present atipically in ASDs then in
general population. Furthermore, they could be mask-
ed by ASD core symptoms.
Keywords: Autistic Spectrum Disorders; Psychiatric
Despite of the increased knowledge about the pathoge-
netic mechanisms and an improvement of the diagnostic
criteria, clinical practitioners have a really poor under-
standing that Autism Spectrum Disorders (ASDs) occur
most frequently than thought in general population
(prevalence rate for all ASD is estimated at 1%) .
ASDs are neurobiological disorders, caused by complex
gene-environment interactions, not yet fully identified
Several studies on patients with ASDs indicate that up
to 70.8% of them are affected by one or more psychiatric
condition in comorbidity . Psychiatric comorbidity
occurs highly in patients with High Functioning Autism
(HFA) and Asperger syndrome (AS) [4-6], which are
milder forms of autism, according to some authors. HFA
individuals have a good cognitive level, expressed by an
IQ > 70. AS is characterized by high verbal IQ, impaired
social interaction, restricted interests and ritualistic be-
haviours, in absence of language delay.
It is still debated if a comorbid d isorder could occur in
ASD patients with a range of different symptoms from
those on es that ar e pathognomon ic in g eneral popu lation.
The identification of psychiatric comorbidity is difficult
in ASD patients: any psychiatric symptoms could overlap
with or be masked by ASD symptoms themselv es.
In this regard, HFA/AS patients could provide clinical
information about their emotional states, due to their
high cognitive level and great verbal communication.
Moreover, those characteristics allow them to attend
mainstream school and so they often experience more
bullying and less social support, which seem to be re-
lated to increasing psychiatric comorbidities, like con-
duct problems and disruptive behavi o rs [ 1] .
On the other hand, it was found that ASDs are much
less recognized and diagnosed in those with milder core
symptoms. HFA/AS patients may therefore present to
health services for other psychiatric symptoms and these
S. Giovinazzo et al. / Open Journal of Psychiatry 3 (2013) 329-334
surface features may not clearly signal the presence of an
According to DSM-IV-TR , ADHD, OCD, schizo-
phrenia are excluded from ASD diagnostic criteria and
diagnosis of anxiety disorders is to be avoided. But many
people with ASD also have a range of psychiatric symp-
toms quite corresponding to diagnostic criteria for those
psychiatric dis order s.
Furthermore, according new DSM-V diagnostic crite-
ria, AS will not be provided for in ASDs. Nevertheless,
we led our study while DSM-IV-TR criteria were still
valid and we could recruit AS patients. However, both
our and the other findings about psychiatric comorbidity
in AS, hereafter should alert clinicians abou t the high risk
of psychopathology in an “AS-like” people, although it
can no longer be considered as “autistic” people.
Have not yet been identified specific risk factors for
the development of co-morbidity in ASDs. Risk factors
that are well recognized in general popu lation to be asso-
ciated with child psych iatric disorders show similar rela-
tionship in children with ASDs . It has been demo-
strated that individuals with less severe ASDs, as HFA
and AS, are equally likely to show additional psychiat-
ric disorders .
Frequently are diagnosed anxiety and depression, be-
havioral disorders like ADHD or oppositional defiant
disorder (ODD) and obsessive disorders [2,8,9]. Some
studies report rare cases of comorbidity with schizophre-
nia and other disorders, including Tourette’s syndrome,
tics, trichotillomania, enuresis or encopresis. Many pa-
tients present multiple comorbid disorders: respectively
80% of ASDs plus ADH D, 60% of ASD s plus behavi oral
disorder, 40% of ASDs plus affective disorder have an-
other or more comorbidities .
2. CLINICAL STUDY
Our clinical study aimed to:
Describe the psychiatric comorbid disorders in a co-
hort of HFA/AS patie nt s;
Define the prevalence of every psychiatric conditio ns
in the sample, comparing our data with the literature;
Identify how many comorbid psychiatric conditions
have arisen in each patient;
Identify a possible relationship between age of pa-
tients and the develop ment of a specific comorbidity;
Assess the drugs used for the treatment of psychiatric
symptoms, defining how many patients needed to set
up a polytherapy.
2.2. Methods and Materials
The sample consisted of 86 HFA/AS patients, examined
at Child Neurology and Psychiatry Unit of Tor Vergata
University, in Rome, from 2009 to 2012.
The patient’s mean age was 14.9 years (median 13.1,
SD 6.7), with a mean age at evaluation of 11.9 years (SD
Male patients were 77 out of 86 (89%), with a male/
female ratio of 8.5.
Autistic symptoms were assessed by comparing the
core clinical features with the DSM-IV diagnostic crite-
ria for ASDs; furthermore, the diagnosis of ASD was
supported by the Autism Diagnostic Observation Sched-
ule (ADOS; Lord et al., 2000) and the Autism Diagnostic
Interview-Revi sed (A D I -R ; L or d et al ., 1995).
Cognitive assessment was performed by the Wechsler
Intelligence Scales (WISC-III; Wechsler, 1991) and non
verbal Leiter International Performance Scale-Revised
(Leiter-R-Visualization and Reasoning, Roid & Miller,
The presence of psychiatric disorders in comorbidity
was evaluated by:
Kiddie-Schedule for Affective Disorders and Schizo-
phrenia (K-SADS; Kaufman et al., 1997), a semi-
structured interview designed to assess present and
past episodes of psychiatric disorders in children and
adolescents between the ages of 6 - 18, according to
Child Behavior Checklist (CBCL) 4/18 years, a ques-
tionnaire completed by parents, about children/ado-
lescent behavioral (e.g. internalizing problems-with-
drawal, somatic complaints, anxiety/depression-, de-
linquent behavior and externalizing behavior aggres-
sive and also attention difficulties, social problems
and thought prob lems);
Conners’ Parent and Conners’ Teacher Rating Scale,
which are questionnaires filled by parents or teachers,
which provide to assess an d quantify oppositional be-
havior, inattention, hyperactivity and ADHD Index;
Swanson, Nolan, and Pelham-IV (SNAP-IV), a ques-
tionnaire designed to assist in diagnosing a child’s
behavioral problems, like Attention Deficit Disorder
with Hyperactivity (ADHD) and Oppositional Defi-
Children’s Depression Inventory (CDI), a brief self-
report test that assesses signs of depression in chil-
dren and adolescents 7 to 17 years old;
Multidimensional Anxiety Scale for Children (MASC),
a self-report test that assesses the presence of symp-
toms related to anxiety disorders in youth aged 8 to 19
In our sample, all 86 subjects were high functioning,
with full scale IQ > 70. Mean IQ was 92.4 (SD = 20.9).
Copyright © 2013 SciRes. OPEN ACCESS
S. Giovinazzo et al. / Open Journal of Psychiatry 3 (2013) 329-334 331
38 patients out of 86 (44.2%) had one or more psy-
Attention deficit/Hyperactivity Disorder (ADHD) was
the most common comorbidity, diagnosed in 25 patients
Were also diagnosed bipolar disorder (n = 7; 18.4%),
depression (n = 2; 5.3%), generalized anxiety disorder
(GAD) (n = 2; 5.3%), positive psychotic symptoms (n =
6; 15.8%), learning disorder (n = 1; 2.6%), obsessive-
compulsive disorder (n = 1; 2.6%), eating disorders (n =
1; 2.6%), oppositional defiant disorder (n = 2; 5.3%), tics
and Tourette’s syndrome (n = 2; 5.3%) (Table 1).
These 38 patients was divided in 3 groups: 1) only
with one comorbidity (71%), 2) with 2 comorbidity
(24%), 39 with 3 or more (5%) (Table 2).
The association between ADHD and Bipolar Disorder
occurred most frequently in patients with multiple
We studied the distribu tion of comorbidities with in the
sample (Table 3), according to four age ranges:
Childhood, including 6- to 8-year and 11 months-old:
n = 7 (18.4% );
Pre-puberty: including 9- to 13-year and 11 months-
old subjects: n = 9 ( 23.7%);
Adolescence, including 14- to 17-year and 11 months-
old subjects: n = 11 (28. 9%);
Adulthood, including 18 years-old subjects and over:
n = 11 (28 .9%).
There was a higher incidence of comorbidity in ado-
lescence. The prevalence of multiple comorbidities in-
Table 1. Comorbid disorders diagnosed in our sample.
Comorbid Disorder Rate of patients (%)
Attention deficit/Hyperactivity disorder 66
Bipolar disorder 18.4
Tics and Tourette’s synd rome 5.3
Generalized anxiety disorder 5.3
Oppositional defiant disorder 5.3
Eating disorder 2.6
Obsessive/Compulsive disorder 2.6
Learning disorder 2.6
Table 2. Rate of patients presenting one or more psychiatric
Comorbid psychiatric disorder Rate of patients (%)
Any psychiatric disorder 44.2%
One psychiatric disorder 71%
Two psychiatric disorder 24%
Three or more psychiatric disorder5%
Table 3. Distribution of comorbidities within our sample,
according to age ranges.
Comorbidity [6,9] ys
18.4% [9,14] ys
23.7% [14,18] ys
28.9% >18 ys
Attention deficit/Hyperact ivity
disorder X X X X
Bipolar disorder X X X
Psychosis X X
Tics and Tourette’s syndromeX X
Generalized anxiety disorder X X X
Oppositional defiant disorder X X
Eating disorder X
Obsessive/Compulsive disorder X
Learning disorder X
creased in puberty and in adolescence.
Every age range was characterized by suffering from
specific types of comorbidity.
Of the 38 patients with comorbidities, 19 (50%) re-
ceived pharmacological treatment. Regarding disrup-
tive behaviours, most of our ASD plus ADHD patients
responded to MPH, one patient did not tolerate that drug
and had to change with atomoxetine, and another patient
was treated only with atomoxetine. The patients with
ODD also were treated with methylphenidate.
Psychotic symptoms were treated with atyical antipy-
chotics, as well as olanzapine or risperidone in most
cases, or aripiprazole in a single case.
The patient with GAD received treatment with par-
oxetine (SSRI) and OCD was treated with sertraline
The patients with depressive disorder received benzo-
diazepines or venlafaxine (NSRI) and that with BD re-
ceived Valproic Acid, which is the first line treatment for
BD in youth. The case of eating disorders was treated
with mirtazapine (NARI). 74% of the cases received a
We compared findings from our study with the evidences
from the scientific literature on psychiatric comorbidity
in individuals with ASD. We consider at first the only
population-study d ealing with several psychiatric co mor-
bidities in ASD subject, involving a population-derived
We found that 44.2% of our HFA/AS patients had co-
morbid psychiatric disorders. Our results differ from the
study of Simonoff et al. : they found that 70.8% of
112 ASD patients had at least one psychiatric comorbid-
ity. However, that sample also included patients with
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S. Giovinazzo et al. / Open Journal of Psychiatry 3 (2013) 329-334
low-functioning autism, which are more frequently and
severely affected by psychiatric symptoms, as well as
disruptive or repetitive behaviours, aggression, irritabil-
ity . Moreover, they employed more effective diag-
nostic tools for screening and diagnosis of psychiatric
disorders in ASD, like Child and Adolescent Psychiatric
Assessment (CAPA; A ngold and Costello, 2000).
In 2009, Mukkades et al.  pointed out a >90%
prevalence of comorbidity in AS and HFA samples: the
high rate was probably due to referral bias in diagnostic
In 2010, Mattila et al.  conducted a study on com-
bined community- and clinic-sample of HFA/AS pa-
tients, aged from 9.8 to 16.3 years. They highlighted a
comorbidity prevalence of 74%, in a cohort aged more
restrictely than ours. We considered also the age corre-
lated with the comorbidity. This correlation is low and
this aspect influenced th e global prevalen ce in our popu-
In our sample, 31% of patients had multiple comorbid-
ities, as compared to 33% reported by Simonoff et al. ,
and to 37% by Mattila et al. . The same comorbidities
have been identified in these studies, as well as in ours:
ADHD, GAD, OCD, ODD, eating behavior disorders,
BD and depression, tics and TS, learning disorders and
psychosis. This recurrent finding of the same associa-
tions between disorders emphasizes that they have a
common genetic and neurobiological substrate. In our
sample, ADHD is the most frequent comorbid disorder
(66%), specially presenting in childhood and puberty. In
literature, the prevalence of ADHD among individuals
with ASD is estimated to be 28.2% , particularly
among those with HFA/AS it’s 44% - 65% . These
findings stress the clinical necessity to assess inattention
and hyperactivity/impulsivity in ASD , and point out
also the fact that often is difficult to establish early diag-
nosis of HFA/AS, because autistic symptoms could be
masked by ADHD symptoms.
The neurobiological point of view shows that ASD
and ADHD are deficits in executive functioning and re-
flect a common dysfunction of fronto-temporal circuits
. ASD and ADHD also share genetic background:
some chromosomal regions such as 2q24, 16p13, 16p1,
17p11, 5p13, 15q have been identified as susceptibility
loci to both ADHD and ASD .
Furthermore, two patients had oppositional defiant
disorder (5.6%), compared to 1% in the study of Simon-
off, to 16% according to Mattila et al. , up to 30%
according Mukkades et al. . Must be considered that
aggression, often found in ODD, is common in ASD pa-
tients, most of all in LFA; moreover, could be the
epiphenomenon of other types of comorbidity, e.g. mood
disorders or anxiety .
Bipolar disorder occurred in 5.2% of cases, specially
in adolescence, as well as other mood disorders. These
data are in accord to the literatu re [13-16] (prevalence of
2% - 9%, usually in adolescence).
Depression occurred in 5.2%, with onset in adulthood,
compared with 0.9% evidenced by Simonoff . De-
pression can often arise with an increase of withdrawal
and aggressive behaviours: these symptoms may present
more clearly in patients with HFA/AS, rather than in
low-functioning autism (LFA), which could primarily
presenting withdrawal and aggression. From other stud-
ies has been reported a very broad range of prevalence of
mood disorders, from 6% up to 70% [4,5,15-19]. This
variability could depend to the fact that some authors
examined only AS patients, other ones considered de-
pressive symptoms rather then a diagnosis of major de-
Only one adolescent patient presented OCD and two
individuals had a GAD (5.26%), one at puberty, the other
at about 18 years. Simonoff et al.  found that 2% of
ASD patients developed a OCD and up to 44% an anxi-
ety disorders. According to the literature, OCD is the
anxiety disorder that appears most frequently in ASD
It is possible to recognize obsessions/compulsions
from ASD repetitive behaviours, , but standardized
diagnostic tools are currently no t yet available.
In our sample, 15.8% of patients presented psychotic
symptoms, with onset in adulthood. In literature, the
prevalence of schizophrenia in ASD is of 0.6% , in
HFA/AS up to 3.3% . In adults with schizophrenia,
there is often a h istory of autistic sympto ms in childhood;
autism and schizophrenia share some neurobiological
abnormalities and genetic back grounds [17,18].
According to all literature examined , tics and
Tourette’s syndrome had an overall prevalence of 22% -
Indeed, TS is considered a risk factor for development
of further neuropsychiatric disorder, in ASD subjects [22,
23]. In our sample, two individuals presented tics only as
About pharmacoterapy in ASDs , atypical antipsy-
chotics or neuroleptics can be effective against aggres-
sion and core symptoms; but it is often necessary to ad-
minister multiple drugs to control comorbid psychiatric
symptoms. Methylphenidate is the first choice for the
treatment of ADHD, benzodiazepines for anxiety symp-
toms, SSRI’s for the treatment of OCD and mood disor-
This study has some limitations, at first by having a
moderate sample size, a too wide age range and no com-
parison group. The age-ranged groups were not well-
matched in gender and number of patients. Second, the
assessment by the parents and children/adolescents may
have resulted in some recall and/or referral bias. Fur-
thermore, we have not distinctly considered current psy-
Copyright © 2013 SciRes. OPEN ACCESS
S. Giovinazzo et al. / Open Journal of Psychiatry 3 (2013) 329-334 333
chiatric diagnosis from past comorbidity.
Third, the present study only provides the rate and
type of psychiatric disorders, and there was no informa-
tion provided regarding associated risk factors such as
family history and life events.
In addition, concerning the diagnostic instruments
used in this study, there are no algorithms precisely for
Regarding to the pharmacological treatment, it would
be necessary to involve and monitorize a larger sample
of treated patients, to verify its short and long term effi-
4. CONCLUSIONS AND FUTURE
There is still no consensus about the belief that symp-
toms of new onset in ASD should be classified as a
manifestati on of furt her psychiatric disor der.
It could be useful to assess the possible common
pathogenetic mechanisms and risk factors between ASDs
and other psychiatric disorders, and to obtain additional
information on the underlying disfunction .
In literature there are only few data about comorbid
psychiatric disorders in ASDs. It could be necessary to
increase the sample size and to collect the largest number
of clinical-anamnestic information, for studying etiopa-
thogenesis and risk factors for the occurrence of comor-
bidity [26,27]; meta-analysis studies would be useful, to
compare individual researches. It would be interesting to
highlight a possible correspondence between age and the
development of a specific comorbid disease. This report
may be useful for lifetime monitoring patients, to predict
the onset of a specific disease, and for early recognition
of symptoms, to plan a focused and effective treatment.
According to some authors, there is need for caution in
interpreting results that use generic measures in higlhy
specific and distinct populations, as well as ASDs, with-
out first characterizing the instrument properties, e.g.
scoring and cut-offs, pertaining to that population .
Clinical practicioners should be able to use diagnostic
tools which are specific for the diagnosis of comorbidity
in ASD patients, to recognize atypical or masked symp-
toms (e.g. Autism Comorbidity Interview Present and
Lifetime version; ACI-PL; Lefeyer et al., 2006; Devel-
opmental Disability Child Global Assessment Scale; DD-
CGAS; Wagner et al., 2007). It would also be necessary
to update the diagnostic criteria for psychiatric disorders
most commonly associated with ASD, adapting them to
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