Review
Psychopathology 2010;43:8–16
DOI: 10.1159/000255958
Psychosis, Affective Disorders and Anxiety
in Autistic Spectrum Disorder: Prevalence and
Nosological Considerations
Norbert Skokauskas a Louise Gallagher b
a
Department of Child Psychiatry, St. James’s Hospital, and b Department of Psychiatry, School of Medicine,
Trinity Centre for Health Sciences, St. James’s Hospital, Dublin, Ireland
Key Words
Autistic spectrum disorders ⴢ Asperger’s syndrome ⴢ
Co-morbidity ⴢ Psychosis ⴢ Mood and anxiety disorders
Abstract
Background: This review aimed to find relevant published
studies on the co-morbidity of autism and Asperger’s syn-
drome with psychotic, anxiety and/or mood disorders, as-
sess them, synthesize the findings, present an overview and
make recommendations for future research. Methods: Sys-
tematic literature searches were performed using several da-
tabases. Selected articles had to describe an original study
that provided prevalence and/or incidence estimates on au-
tism and/or Asperger’s syndrome co-morbidity with psy-
chotic, anxiety and/or mood disorders. Results and Conclu-
sion: There is conflicting evidence regarding the frequency
of schizophrenia in this population. Depression appears to
be common, although most individuals with autism do not
have sufficient language skills to verbalize changes in mood.
Anxiety disorders represent the most common psychiatric
co-morbidity in this population.
Copyright © 2009 S. Karger AG, Basel
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Received: July 3, 2008
Accepted after revision: March 3, 2009
Published online: November 6, 2009
Autistic spectrum disorders, classified as pervasive
developmental disorders in ICD-10 and DSM-IV, are rel-
atively common social communication disorders that af-
fect up to 0.5% of individuals. Autistic disorder, atypical
autism and Asperger’s syndrome (AS) are all autistic
spectrum disorders (ASDs). The essential features of au-
tistic disorder are the presence of markedly abnormal or
impaired development in social interaction and commu-
nication and a markedly restricted repertoire of activity
and interests. Severe and sustained impairment in social
interaction and the development of restricted, repetitive
patterns of behaviour, interests and activities are the es-
sential features of Asperger’s disorder [1].
In the past there was a tendency to attribute all psychi-
atric problems in children and adults with autism to au-
tism itself [2]. Possible reasons were that the diagnosis of
these disorders encompasses such a severe and compre-
hensive label that secondary, tertiary or subsequently ap-
pearing psychiatric problems were not viewed as pivotal
[3]. However, an increasing number of investigators are
arguing for accepting behaviours and symptoms that had
been considered additional or associated features of ASDs
as potentially indicating the presence of co-morbidities
warranting additional diagnosis [4]. Despite the recent
increase in studies on the occurrence of medical and neu-
Norbert Skokauskas and Louise Gallagher
Dept. of Psychiatry, School of Medicine
Trinity Centre for Health Sciences, St. James’s Hospital
Dublin D-8 (Ireland)
Tel./Fax +353 1 414 4802, E-Mail N_Skokauskas@yahoo.com
rological conditions in persons with autism and AS, less
is known about the rates of psychiatric co-morbidity.
A strong genetic component of autism has been dem-
onstrated by a number of clinical genetic studies showing
an increased concordance rate in monozygotic compared
to dizygotic twins as well as an increased risk to siblings,
relative to the general population prevalence, and herita-
bility for autism has been estimated at 80–90% [5–7]. It is
not clear if genetic factors play a role in the development
of psychiatric co-morbidities in people with ASD, al-
though there is clear evidence that axis I psychiatric di-
agnoses occur with greater frequency in the first-degree
relatives of individuals with autism, perhaps suggesting a
broader heritability for psychiatric disorder [8, 9]. Better
understanding of the psychiatric co-morbidity of ASD
could indicate directions for further studies to find shared
genetic vulnerabilities.
There is no doubt that co-morbid conditions can com-
plicate patient management. So accurate, reliable diagno-
sis of co-morbid psychiatric disorders in children with
autism is of major importance. When problematic behav-
iours are recognized as manifestations of a co-morbid
psychiatric disorder, rather than just isolated behaviours,
more specific treatment is possible [10].
Sources of artifact in the detection of co-morbidity be-
tween psychiatric disorders have been well described pre-
viously. Briefly, issues such as methodological shortcom-
ings (for example referral and screening/surveillance bi-
ases) and nosological confusion are a potential source of
confounding variables [11, 12].
A summary review of the literature revealed a consid-
erable number of studies covering morbidity both with
psychiatric disorder and other early-onset neurodevelop-
mental disorders of childhood such as attention deficit
hyperactivity disorder and tic disorders. The overlap of
early-onset neurodevelopmental disorders has been the
subject of in-depth discussion elsewhere [13, 14]. In con-
ducting this review we were predominantly concerned
with the overlap with psychiatric disorders such as psy-
chotic, affective and anxiety disorders, arising from sub-
stantial uncertainty regarding the extent and nature of
co-morbid psychiatric symptoms due to disparate find-
ings in previous studies.
Methods
PubMed, PsychINFO, EMBASE, Science Direct and Ovid On-
line were searched from database inception through May 2008
using the following key words: autism, autistic disorder, Asper-
ger’s syndrome, co-morbidity, schizophrenia, psychosis, psychot-
Psychiatric Co-Morbidity of Autism and
AS
ic disorder, mood disorders, bipolar affective disorder, depres-
sion, mania, anxiety disorder and obsessive-compulsive disorder
(OCD). A hand search of relevant journals and books was also
performed. Additional papers were selected by checking the refer-
ence lists from identified papers. The search continued until it
was clear that no new references were being retrieved. The search
was confined to English language articles.
Selected articles, as a criterion for inclusion, had to describe
an original study that provided a prevalence and/or incidence es-
timate of the occurrence of co-morbidity, i.e. psychotic, anxiety
and/or mood disorders in autism and AS. No limits were placed
on the demographics, e.g. geographical, gender, age or size of the
study populations.
Results
Using the above criteria, 27 studies were identified,
reviewed and included in this paper. Although the stud-
ies met the inclusion criteria, they differed considerably
in the diagnostic criteria employed, sample size, sam-
pling methods and subjects’ demographics.
Despite such heterogeneity this review provides an up-
date on autism and/or AS co-occurrence with psychotic,
anxiety and/or mood disorders. It also reflects problems
with research in the area.
Schizophrenia and AS/Autism
In the past, autism was regarded as being on a con-
tinuum with schizophrenia, and the term ‘childhood
schizophrenia’ was widely used. Epidemiological follow-
up studies that compared early- with later-onset psycho-
sis prompted the emergence of greater differentiation be-
tween schizophrenia and ASDs [15, 16]. Differences in
the presenting characteristics, course, level of intellectual
functioning, sex distribution, age at onset, organicity and
family history of schizophrenia were detected, and it was
concluded that autism and schizophrenia were in fact dis-
tinct disorders. However, there is persisting evidence that
individuals developing early-onset schizophrenia may
show pre-morbid features of autism; moreover, the simi-
larities between some symptoms in adults with autism
and the negative symptoms of schizophrenia have been
highlighted [17]. The question remained as to whether for
some individuals at least, having an autistic spectrum
might place them at increased risk of schizophrenia/psy-
chosis. Studies have tried to address this question through
the observation of co-occurrence of autism and schizo-
phrenia. Asperger [18] originally reported only 1 indi-
vidual from 200 cases with AS who developed symptoms
of schizophrenia. Wing [19] detected 1 case out of 18 AS
patients with psychosis, 1 with catatonic stupor and 1 had
Psychopathology 2010;43:8–16 9
bizarre behaviour and an unconfirmed diagnosis of
schizophrenia. These early studies were followed by more
systematic attempts to investigate co-occurrence rates,
although these have yielded conflicting findings. Wolff
and Chick [20] followed up 22 people with AS detecting
1 with an apparently typical schizophrenic illness and a
second with a possible diagnosis. A further follow-up
study of 14 men with histories of infantile autism found
no evidence of positive symptoms of schizophrenia [21].
A third study found 1 case of schizophrenia in 16 high-
functioning autism patients [22]. Larsen and Mouridsen
[23] reported 1 case of schizophrenia in a sample of 18
children fulfilling the ICD-10 criteria for childhood au-
tism (n = 9) and AS (n = 9) over a period of 30 years. The
occurrence of schizophrenia/psychosis in ASD in these
studies, although clearly underpowered, varied between
0 and 6%.
Larger studies however have also demonstrated wide
variability in the rates of reported diagnosis of schizo-
phrenia in autism. In a follow-up study of 85 adults with
Asperger’s disorder, Tantam [24] noted that 3 cases of
schizophrenia in 85 adults with Asperger disorder and a
further 6 cases of psychosis (4 with hallucinations, 1 with
psychosis in the context of temporal lobe epilepsy; 2 with
depressive psychosis). This contrasts with at least 4 other
studies, all of which failed to identify a substantial num-
ber of cases of schizophrenia. Examination of the case
records of 163 adolescents and adults with autism identi-
fied 1 individual (0.6%) with an unequivocal history of
schizophrenia [25]. Ghaziuddin [26] reported no cases of
schizophrenia out of 68 individuals with autistic disor-
der. No cases of schizophrenia were identified in a longi-
tudinal study of 74 autistic adults [27]. Leyfer et al. [10]
reported that none of 109 autistic children included in
their study met DSM-IV criteria for schizophrenia or for
psychotic disorder. Thus, it appears that the higher rates
in earlier studies were not replicated in subsequent larger
trials.
Using an alternative strategy to investigate overlap
between autism and schizophrenia, Konstantareas and
Hewitt [28] conducted the Structured Clinical Interview
in a sample of 14 males with autism and 14 with schizo-
phrenia. None of the men with paranoid schizophrenia
met criteria for autism, while 7 of those with autism met
criteria for schizophrenia, disorganized type, showing
negative symptoms, 5 had positive symptoms and 6 had
negative symptoms. On face value this might suggest that
the symptoms of schizophrenia may occur more fre-
quently in AS. However, the results also prompt an im-
portant nosological question with respect to the accuracy
10 Psychopathology 2010;43:8–16
of the Structured Clinical Interview in differentiating be-
tween symptoms of autism and symptoms of schizophre-
nia. Taking another perspective, McKenna et al. [17] in-
vestigated the occurrence of AS in children and adoles-
cents with childhood-onset psychosis using systematic
clinical and structured interviews. While 4 cases were
identified as having AS, they did not meet operational
criteria for schizophrenia.
Thus, the reports concerning co-occurrence rates be-
tween autism and schizophrenia/psychosis vary widely
in the literature with respect to incidence and prevalence
(table 1).
A number of questions arise with respect to the meth-
odologies of these studies, i.e. how comparable the stud-
ies were in terms of sample selection and ascertainment
and in their definition and detection of caseness.
Mood (Affective) Disorders
The caveats that apply to symptoms of psychosis in AS
apply also to the detection of symptoms of affective dis-
orders. At baseline, some individuals with autism or AS
who are not depressed are quiet, socially withdrawn and
lack facial expression [19]. Furthermore, many individu-
als with autism and AS will not have sufficient language
skills to verbalize changes in mood and feelings of de-
pression. It has been argued that autistic children and
adults with depression do not present clinically until the
depression is quite severe and/or prolonged [27].
Kanner [29] noted in his original series that at least 1
person showed a tendency to lapse into a ‘momentary fit
of depression’, and a few children described by Asperger
[18] had depressive features. Early smaller studies report-
ed rates of affective disorder in 4–8 out of 18 cases [19]
and no cases out of 14 men with autism [21]. The latter
study, however, identified affective symptoms with half
the sample presenting with affective flattening. A third
study (n = 18) found 1 child with autism and 1 with AS
had a history of depression [23]. A larger study that fol-
lowed up 66 children with autism identified 9% with ‘def-
inite symptoms of depressive mood’, although not de-
fined in terms of diagnostic criteria [30]. Ghaziuddin [26]
identified 3 out of 68 autistic individuals with a mood
disorder (2 suffered from major depressive disorder and
1 from depression not otherwise specified). In a later
study by the same author, higher rates of co-occurrence
were detected, 8 out of 35 individuals with AS were diag-
nosed as having major depression, and 1 other individual
had bipolar affective disorder (BPAD) [31]. Studies using
parental report variably identified 1 out of 20 individuals
who met ICD-10 criteria for depression [32] and 10 out of
Skokauskas /Gallagher
Table 1. Psychotic disorders and AS/autism
Authors Study
Asperger [18], 1944 Follow-up of 200 AS children
Wolff and Chick [20], 1980 22 AS children (author’s series)
Wing [19], 1981 18 AS children and adults (author’s
series)
Rumsey et al. [21], 1985 Follow-up of 14 men with autism
Szatmari et al. [38], 1989 Follow-up of 16 children with autism
Volkmar and Cohen [25], 163 adolescents and adults with autism
1991 (retrospective charts review)
Tantam [24], 1991 Follow-up of 85 adults with AS
Ghaziuddin [26], 1992 68 children and adolescents with autistic
disorder (cross-sectional)
Larsen and Mouridsen [23], Follow-up of 9 AS and 9 children with
1997 autism
Howlin [27], 1997 Follow-up of 74 autistic adults
Konstantareas and Hewitt 14 males with autism (cross-sectional)
[28], 2001
Leyfer et al. [10], 2006 109 children with autism (cross-sectional)
59 (16.9%) children with autism and AS [33]. A further
study using self-report determined rates of 18% in 33 in-
dividuals with AS using the Children’s Depression Inven-
tory [34], while a case record review (n = 100) found 3
individuals had a diagnosis of depression [35]. A cross-
sectional study using a self-administered mail- and Web-
based questionnaire (n = 10) identified 20% who met cri-
teria for a diagnosis of major depressive disorder [36].
Leyfer et al. [10] reported that 10% of the children with
autism had had at least 1 episode of major depression
meeting DSM-IV criteria. When subsyndromal cases
were included, the rate of major depression increased to
nearly 24%. The relative advantage of the approach used
here was the attempt to standardize diagnoses of co-mor-
bidity using a modified version of the Kiddie Schedule for
Affective Disorders and Schizophrenia. Thus, identifica-
tions of depression in ASD show similarly wide variabil-
ity in the range of co-occurrence as those reported in
schizophrenia/psychosis, i.e. almost 0 to exceptionally
high rates of 40–50%. Furthermore, it is not always clear
from studies where the cut-off lies between an ICD or
DSM-IV diagnosis and the presence of negative affective
symptoms.
Similar difficulties encountered in relation to the iden-
tification of psychosis apply to the identification of mania
or hypomania in autism/AS. Hypomania may be con-
Psychiatric Co-Morbidity of Autism and
AS
Findings
1 developed schizophrenia
1 was diagnosed as having schizophrenia
1 developed psychosis, 1 had an episode of catatonic stupor
and 1 had an unconfirmed diagnosis of schizophrenia
Positive schizophrenic symptoms were absent at follow-up
1 patient had schizophrenia
1 individual had an unequivocal history of schizophrenia
3 developed schizophrenia, 4 hallucination, 1 epileptic
psychosis and 2 depression psychosis only
Nobody was diagnosed as having schizophrenia
1 autistic patient developed schizophrenia
None developed schizophrenia
7 of those with autism met criteria for schizophrenia,
disorganized type, showing negative symptoms
None met DSM-IV criteria for schizophrenia
fused with the tendency of some individuals with AS or
autism to talk in a excited manner about their fantastic,
grandiose, imaginary ideas or preoccupations [19].
Though mania and hypomania with and without associ-
ated depression have been reported in a number of case
reports of individuals with pervasive developmental dis-
orders, there are only a few studies of mania in subjects
with autism or AS [2].
Investigations of manic or hypomanic symptoms have
produced again large ranges in terms of co-occurrence
rates varying from approximately 21% [37] to 2% [10]. In
Tantum’s [24] study, approximately 5% developed mania
only, 5% mania and depression, 2.3% depressive psycho-
sis (as mentioned above), 6% depression only, and 2.3%
depression and anxiety (table 2).
Anxiety Disorders
Generalized anxiety is a common feature of autism/
AS, and a diagnosis of generalized anxiety disorder is
precluded by DSM-IV if a pervasive developmental dis-
order is present [1]. This has limited the number of stud-
ies which have investigated the occurrence of anxiety
symptoms defined by DSM-IV.
Generalized anxiety disorder was reported in 35% of
adolescents with AS (n = 19) based on ICD-10 criteria for
generalized anxiety disorder [32]. Lower rates of 13.6%
Psychopathology 2010;43:8–16 11
Table 2. Mood (affective) disorders and AS/autism

Authors Study Findings

Kanner [29], 1943 11 children with autism (cross-sectional in At least 1 person showed a tendency to lapse into a ‘momen-
1943, follow-up in 1973) tary fit of depression’
Wing [19], 1981 18 AS children and adults (author’s series) 4 subjects had affective illness; a further 4 had become in-
creasingly odd and withdrawn, probably with underlying
depression
Rumsey et al. [21], 1985 Follow-up of 14 men with autism Although none met DSM criteria for affective disorder,
several showed various affective symptoms
Chung et al. [30], 1990 Follow-up of 66 autistic children 9% with ‘definite symptoms of depressive mood’, although
not defined in terms of diagnostic criteria
Tantam [24], 1991 Follow-up of 85 adults with AS 4 developed mania only; 4 mania and depression; 2 depres-
sion psychosis only; 5 depression only; 2 depression and
anxiety
Ghaziuddin [26], 1992 68 children and adolescents (cross- 3 had a mood disorder (2 major depressive disorder and 1
sectional) depression not otherwise specified)
Wozniak et al. [37], 1997 66 children with autism (cross-sectional) 14 were diagnosed as having mania
Larsen and Mouridsen Follow-up of 9 AS and 9 children with 1 child with autism and 1 child with AS had a history of
[23], 1997 autism depression
Ghaziuddin et al. [31], Follow-up of 35 children with AS 8 individuals were diagnosed as having major depression;
1998 1 had bipolar affective disorder
Green et al. [32], 2000 20 adolescents with AS (cross-sectional) 1 attained criteria for depression and 5 for dysthymia
Kim et al. [33], 2000 59 children with autism and AS (cross- 16.9% of the children scored at least 2 standard deviations
sectional) above the mean on a parent report measure of depression
Barnhill [34], 2001 33 adolescents with AS (descriptive study) 36% reported fewer depressive symptoms than peers, 18%
reported more depressive symptoms than peers
Cederlund and Gillberg 100 males with AS (retrospective charts 3 patients had a diagnosis of depression
[35], 2004 review)
Leyfer et al. [10], 2006 109 children with autism (cross-sectional) 10% of the children with autism had had at least 1 episode of
major depression, 2 met diagnostic criteria for manic epi-
sode and 1 for hypomanic episode, 2 patients were diag-
nosed as having BPAD 1, and 1 patient was diagnosed as
having BPAD 2, and 2 suffered from mixed episode
Shtayermman [36], 2007 10 adolescents and young adults diagnosed 20% met criteria for a diagnosis of major depressive disorder
as having AS (cross-sectional)

for generalized anxiety disorder were reported in a study
using a parent report measure [33]. Shtayermman [36]
found 30% of subjects with AS met criteria for general-
ized anxiety disorder. Other studies have used the term
‘overanxious’ and detected this in 17% of cases with AS
and in 10% of cases with high-functioning autism [38].
Lower levels were detected in Tantam’s [24] study, which
reported 4 cases with anxiety (5%) and 2 (2.5%) with de-
pression and anxiety.
Muris et al. [39] examined the presence of co-occur-
ring anxiety symptoms in 44 children with ASDs and
found that 84.1 % met criteria for at least 1 anxiety disor-
der. Simple phobia (63.6%) was the most common anxiety
disorder. One other study reported ‘definite symptoms of
fear/phobia’ in 23% of cases, although these were not
measured in a standardized way [30]. Szatmari et al. [38]
identified 10% who met the criterion for a specific pho-
bia.
A case-control study assessed autism cases (n = 29),
cases with anxiety disorder (n = 30) and normal controls
(n = 34) using self- and parental report. Significantly
higher levels of anxiety in both the AS group and the
anxiety disorders group were detected compared with
controls. Negative thoughts, behavioural problems and
life interference were significantly higher for the AS
group than for the 2 comparison groups [40]. Leyfer et al.

12 Psychopathology 2010;43:8–16 Skokauskas /Gallagher

Table 3. Anxiety disorders and AS/autism

Authors Study Findings

Szatmari et al. [38], Follow-up of 16 high-functioning autistic 4 patients (25%) were overanxious and 3 (19%) had OCD
1989 children
Szatmari et al. [38], 28 children with AS and 25 with high- 8% of the children with AS and 10% of children with high-
1989 functioning autism (cross-sectional) functioning autism were diagnosed as having OCD and 17%
of the children with AS and 10% with high-functioning au-
tism were overanxious
Chung et al. [30], 1990 Follow-up of 66 autistic children 23 % had ‘definite symptoms of fear/phobia’, although these
were not measured in a standardized way
Tantam [24], 1991 Follow-up of 85 adults with AD 4 had anxiety only; 2 had depression and anxiety, 2 developed
OCD
Ghaziuddin [26], 1992 68 children and adolescents (cross- 1 person was diagnosed as having OCD
sectional)
Ghaziuddin et al. [31], Follow-up of 35 children with AS 1 person was diagnosed as having OCD
1998
Muris et al. [39], 1998 44 children with ASDs (cross-sectional) 84.1% of the children met criteria for at least 1 anxiety disor-
der; simple phobia (63.6%) was the most common anxiety
disorder
Green et al. [32], 2000 20 male adolescents with AS 35% generalized anxiety disorder, 10% specific phobia and
25% OCD
Kim et al. [33], 2000 59 children with autism and AS (cross- 13.6% of the children scored at least 2 standard deviations
sectional) above the mean on a parent report measure of generalized
anxiety and on the internalizing factor, which included gener-
alized anxiety, separation anxiety and depression
Leyfer et al. [10], 2006 109 children with autism (cross-sectional) 44% met diagnostic criteria for specific phobia; fear of needles
and/or shots and crowds were the most common; 11.9% met
criteria for separation anxiety, 37% had OCD
Shtayermman [36], 2007 10 adolescents and young adults diagnosed 30 % of the subjects with AS met criteria for generalized anxi-
as having AS (cross sectional) ety disorder
Cath et al. [44], 2008 12 adults with ASD (cross-sectional) ASD subjects had either a co-morbid OCD (n = 6) or comor-
bid social anxiety (n = 6)

[10] reported that the most common DSM-IV lifetime di-
agnosis in the autism sample was specific phobia. Forty-
four percent of the children with autism met diagnostic
criteria. Fear of needles and/or shots and crowds were the
most common (32%).
OCD is a form of anxiety as defined by the official sys-
tems of classifications [1, 41]. Obsessiveness has been re-
garded as either part of autism/AS or chance occurrence.
In AS the fixations and idiosyncratic interests are not ac-
companied by inner distress; in fact, these interests are
often pleasurable. Moreover, compulsions are more com-
mon compared to obsessive thoughts. This is in contrast
to OCD, where the symptoms often cause distress and
anxiety [1]. However, it has been noted that subjects with
a high-functioning autism or AS could develop classical
OCD in parallel [42].
Some studies have reported relatively low rates of
OCD in AS ranging from 2 out of 85 adults, 1 out of 68
autistic individuals and 1 out of 35 individuals with AS
[24, 31, 43]. However, Leyfer et al. [10] identified OCD
as the second most frequent DSM-IV disorder in their
study, where it was diagnosed in 37% of the children
with autism. The most common type of compulsion,
seen in almost half of the children diagnosed as having
OCD in this study, were ritualistic and involved others
having to do things a certain way. Cath et al. [44] inves-
tigated which symptoms discriminate between OCD
and social anxiety with versus without a co-morbid ASD
in clinical setting and reported that ASD subjects (12)
had either a co-morbid OCD (n = 6) or co-morbid social
anxiety (table 3).

Psychiatric Co-Morbidity of Autism and Psychopathology 2010;43:8–16 13

AS
 Discussion
Several studies attempted to investigate the co-mor-
bidity of autistic disorder and AS with anxiety, psychotic
and mood disorders. These attempts differed in sample
size, sampling methods, subjects’ demographics and di-
agnostic criteria employed. Even ICD-10 and DSM-IV
differ in terms of ASD classification and diagnostic cri-
teria used, for example the diagnostic criteria employed
for atypical autism in ICD-10 are not exactly equivalent
to pervasive developmental disorder not otherwise spec-
ified in DSM-IV. It should also be considered that the re-
views span almost 3 decades of research, and in this time
there has been considerable broadening out of the diag-
nostic criteria for autism and ASD [7]. The implication
for the review presented here is that it has not been pos-
sible to be entirely systematic about the diagnostic groups
included. This has been further compounded by the fact
that it was difficult to glean from many studies whether
individuals had intellectual disability or were verbal or
non-verbal. Given the variable approaches, it is not sur-
prising that this is reflected in the wide ranges in rates of
co-occurring symptoms or diagnoses; 0–6% for schizo-
phrenia, 0–50% for affective disorders or symptoms, 5–
35% for generalized anxiety, 10–64% for simple phobias
and 1–37% for OCD.
A common drawback of the reviewed studies is that
they did not investigate co-morbidity as a primary ques-
tion. Hence the majority did not address sources of arti-
fact in the detection of co-morbidity, which have been
previously described [11, 12]. A detailed discussion is be-
yond the scope of this review, but methodological short-
comings (for example referral and screening/surveillance
biases) and nosological confusion (the use of categories
where dimensions might be more appropriate, overlap-
ping diagnostic criteria, artificial subdivision of syn-
dromes, one disorder representing an early manifestation
of the other, and one disorder being part of the other) are
a potential source of confounding variables [12].
Many of the studies reported here used relatively small
and highly selected clinical samples. The latter arguably
will contain a disproportionate number of cases with co-
morbidity [45]. Moreover, tertiary referral centres seeing
complicated cases are likely to have a disproportionately
high level of co-morbidity [12]. Reliance on these types of
cases in the studies reported here may account for the
higher co-occurrence rates observed.
It has been discussed above how there has been a shift
away from the view of autism on a continuum with
schizophrenia towards separation of the 2 conditions into
14 Psychopathology 2010;43:8–16
distinct categorical entities. What remains unclear is how
aspects of the phenomenology of the 2 disorders differ,
e.g. the difference between a delusion and rigid thinking.
It is therefore not surprising that there is conflicting evi-
dence regarding the frequency of schizophrenia among
people with autism/AS. One important issue to consider
is the differing study designs utilized in the studies re-
ported here, i.e. longitudinal follow-up and chart reviews.
It is puzzling that small, probably underpowered studies
have detected individuals with schizophrenia (more than
expected in the general sample), while at least 2 larger tri-
als (n = 74 and n = 109) found no individual with this
disorder despite expectations of at least 1 or 2, and the
largest study (n = 163) detected 1 individual (0.6%) [10,
25, 27]. Again the likely explanation here is the effect de-
scribed by Berkson [45].
The studies by Konstantareas and Hewitt [28] and
McKenna et al. [17] raise interesting questions with re-
spect to the nosology of the 2 disorders. Konstantareas
and Hewitt identified symptoms in the autistic sample
that might also be defined as ‘schizophrenic’ in a struc-
tured interview suggesting perhaps that there are over-
laps in symptoms between the 2 disorders, or at least in
terms of how they are defined in the interview being uti-
lized. McKenna et al. identified a higher than expected
number of individuals with AS in 71 patients with early-
onset psychosis. It is possible that overlapping symptoms
might be suggested and possibly more likely to appear
when the psychotic illness has occurred earlier in the de-
velopmental trajectory.
Most studies reported that depression was common,
affecting up to a quarter in 1 sample [10]. It is interesting
that such high rates are reported, given that many indi-
viduals with autism do not have sufficient language skills
to express their feelings, describe changes in mood or
comment on the presence of biological symptoms of de-
pression. Even verbal individuals with AS may be im-
paired in the reporting of these symptoms, given the
presence of deficits in socio-emotional communication.
As noted above, some of the symptoms that are charac-
teristic of autism or AS, e.g. social withdrawal, limited
facial expression and flattened affect, also are features of
depression. It might be argued that ‘baseline autistic
mood’ could be very similar to depressed mood, and
while it is not easy to notice and assess mood changes in
autistic subjects, one possibility is that high rates of de-
pression in this population could be reporting bias.
Very few studies have looked at and reported on au-
tism/AS co-morbidity rates with bipolar affective disor-
der and manic episode. Some studies included probands
Skokauskas /Gallagher
with very early age at onset, which complicates the dif-
ferentiation between non-specific behaviours and emo-
tions that occur in some young children with AS (irrita-
bility, overactivity, distractibility, lack of fear of danger,
sleep problems, over-talkativeness and social disinhibi-
tion) and symptoms of mania [2]. Other 2 studies report-
ed lower prevalence rates for mania approaching popula-
tion prevalence [10, 24]. Clearly this is an area requiring
refinement in terms of the types of symptoms that are
indicative of co-morbid mania, and further investigation
is also required.
This review found anxiety disorders to be the most
commonly detected psychiatric disorders in subjects with
autism and AS. As with depressed mood, the boundaries
between anxiety symptoms in autism/AS and anxiety
disorder co-existing with autism/AS have not been clear-
ly outlined by studies to date and are likely to contribute
to the exceptionally high levels of anxiety disorders re-
ported to co-occur.
Many studies reviewed above had methodological
shortcomings. First of all most of them had small sample
sizes with no power considerations. Some studies had un-
clear statistical methods or inclusion criteria. Also there
is the question if the studies used appropriate methods of
detection of psychiatric co-morbidity. Certainly a hetero-
geneous approach to defining psychiatric co-morbidity
was observed.
Most studies discussed here did not address co-mor-
bidity as a primary question, and many trials were not
optimally designed. Appropriate study designs will re-
quire larger samples of well-diagnosed cases. Future ap-
proaches might include cross-sectional studies of a large
sample or a longitudinal study design and are likely to be
costly. Given the small samples reported to date, further
investigations would benefit from a coherent approach
across a number of sample collections that might allow
for collaborative analysis or meta-analysis.
Increasingly investigators are arguing for accepting
behaviours and symptoms that had been considered ad-
ditional or associated features of ASDs as features of co-
existing neuropsychiatric disorders. However, it appears
that nosological considerations need to be addressed; it is
difficult to determine if symptoms are part of the phe-
nomenology of both conditions, similar between the con-
ditions or occurring co-morbidly. Recently a clinical in-
strument for the assessment of co-morbid psychiatric
disorder and autism has been developed, e.g. the Autism
Co-Morbidity Interview – present and lifetime version
[10]. Instruments such as this may distinguish impair-
ment due to co-morbid psychiatric disorders from im-
pairment due to core features of autism and potentially
will be useful in the assessment and quantification of co-
morbidity in future studies [10]. However, the above-de-
scribed instrument remains in its initial developmental
phase and has not been widely used and validated. So a
need for appropriate measures for the autistic/AS popula-
tion that will more precisely detect psychiatric co-mor-
bidity remains actual. Furthermore, as discussed above,
family members of individuals with autism appear to
have a greater liability towards psychiatric disorder, with
OCD, social phobia and affective disorder most prevalent
[8, 46]. This observation appears unrelated to the pres-
ence of the broader autism phenotype and the burden of
caring for a child with autism. Studies to date have not
directly reported the association between psychiatric co-
morbidity in individuals with autism and the occurrence
of psychiatric disorder in their relatives. Since autism has
a heterogeneous aetiology with evidence for a polygenet-
ic inheritance [47], further investigation of the possible
genetic contribution to psychiatric disorders in individu-
als with autism and first-degree relatives is merited.
Thus, in order to carefully investigate and assess the
psychiatric co-morbidity of AD/autistic disorder, better-
designed studies with larger samples using appropriate
measures are needed. The advantage will be better detec-
tion which may lead to targeted treatment of psychiatric
co-morbidities in autistic/AS patients and improve their
functioning and quality of life.

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