DSM-5 ASD Moves Forward into the Past

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J Autism Dev Disord
DOI 10.1007/s10803-013-1870-3

 ORIGINAL PAPER

DSM-5 ASD Moves Forward into the Past
Luke Y. Tsai • Mohammad Ghaziuddin

Ó Springer Science+Business Media New York 2013

Abstract The fifth edition of the diagnostic and statistical   Historical Perspective
manual of mental disorders (DSM-5) (APA in diagnostic
and statistical manual of mental disorders, Author, Wash-      Jean Itard’s Wild Boy of Aveyron—historical accounts
ington, 2013) has decided to merge the subtypes of per-        have shown that ‘‘autism’’ has been part of the human
vasive developmental disorders into a single category of       condition at least since the mid-1300s as illustrated by the
autism spectrum disorder (ASD) on the assumption that          famous case of Victor, the wild boy of Aveyron (see Itard
they cannot be reliably differentiated from one another.       1962; Malson 1972). Victor was abandoned in the forest
The purpose of this review is to analyze the basis of this     for about 2 years before he was ‘‘rescued’’ and admitted to
assumption by examining the comparative studies between        the National Institute for Deaf Mutes in Paris at the age of
Asperger’s disorder (AsD) and autistic disorder (AD), and      12 years. After several months to communicate with him
between pervasive developmental disorder not otherwise         and to modify his primitive behavior failed, many of the
specified (PDDNOS) and AD. In all, 125 studies compared        leading physicians of France declared that he was an
AsD with AD. Of these, 30 studies concluded that AsD and       ‘‘idiot’’ with a ‘hopeless’ prognosis (Cohen 1997). Jean
AD were similar conditions while 95 studies found quan-        Marc Gaspard Itard, a brilliant physician, was then asked to
titative and qualitative differences between them. Like-       educate him. At the end of 2 years, Victor showed major
wise, 37 studies compared PDDNOS with AD. Nine of              gains in socialization and self-care. He could display
these concluded that PDDNOS did not differ significantly       genuine affection for his caretakers and even read a few
from AD while 28 reported quantitative and qualitative         words. Itard worked with Victor for 5 years, but was not
differences between them. Taken together, these findings       able to help him attain the capacity for human speech.
do not support the conceptualization of AD, AsD and            Since then, many children resembling Victor have been
PDDNOS as a single category of ASD. Irrespective of the        described with, social and communication deficits, sensory
changes proposed by the DSM-5, future research and             abnormalities, and stereotypic behaviors, who would
clinical practice will continue to find ways to meaningfully   probably be diagnosed today as having autism.
subtype the ASD.                                                   Leo Kanner’s early infantile autism—in 1943, Leo
                                                               Kanner, an Austrian psychiatrist who immigrated to the
Keywords DSM-5  Autism spectrum disorder  Autistic           United States in 1924, published his now classic paper,
disorder  Asperger’s disorder  Pervasive developmental       ‘‘Autistic Disturbance of Affect Contact,’’ which described
disorder not otherwise specified                               a group of 11 physically normal children with a previously
                                                               unrecognized disorder. He noted a number of characteristic
                                                               features in these children, such as an inability to develop
                                                               relationships with people, extreme aloofness, a delay in
                                                               speech development, and non-communicative use of
L. Y. Tsai (&)  M. Ghaziuddin
                                                               speech. Other features included repeated simple patterns of
Department of Psychiatry, University of Michigan Medical
School, 2385 Placid Way, Ann Arbor, MI 48105, USA              play activities and islets of ability. He described these
e-mail: lyctsai@umich.edu                                      children as having ‘‘come into the world with innate

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inability to form the usual, biologically provided affective      condition was never recognized in infancy and early
contact with people’’ (Kanner 1943, p. 250).                      childhood and that those with the syndrome had excellent,
    Despite the variety of individual differences that            logical abstract thinking and were capable of originality
appeared in the case descriptions, Kanner believed that           and creativity in chosen fields. The case histories also
only two features were of diagnostic significance: autistic       indicated the presence of developmental delay and/or
aloneness and obsessive insistence on sameness. He                social and behavioral difficulties from an early age.
adopted the term early infantile autism to describe this              Asperger subtly changed his descriptions of his syn-
disorder and called attention to the fact that its symptoms       drome over the years, perhaps affected by the opinions of
were already evident in infancy.                                  other authors. In his later paper (1979) he emphasized the
    Hans Asperger’s Autistic Psychopathy—Hans Asperger            high intelligence and special abilities in areas of logic and
was also born and educated in Austria. He was trained as a        abstraction, whereas, in 1944, he had specified that his
pediatrician but was later appointed as the director of the       syndrome could be found in people of all levels of intel-
Unit for Special Education at the Children’s Hospital. In         ligence, including those with mental retardation.
1944, after more than a decade of working at the hospital,            Asperger’s work remained relatively unknown (though
he described four boys, aged 6–11 years, in his post-             referred to by Rimland 1964; Rutter 1978; Van Krevelen
graduate thesis (in German), ‘‘Die ‘Autistischen Psychop-         1971; and Wing 1976a, b) in English-speaking countries
athen im Kindesalter’’ (autistic psychopathy in childhood).       until 1981 when Lorna Wing, a British psychiatrist, pub-
However, it appears that in 1926 Dr. G. E. Ssucharewa             lished an influential review of the topic and added a series
(Ssucharewa and Woll 1996), a Russian neurology scien-            of her own (Wing 1981).
tific assistant, published the first case report (in German) of       Infantile Psychosis and Childhood Schizophrenia in Pre-
six boys, ages 10–13 years, with clinical features resem-         DSM-III and ICD-9 Era—about two decades after Kanner
bling those later described by Asperger (1944). However,          (1943) and Asperger (1944) publish their cases, clinicians
Asperger was not aware of her work when he published his          in the United States and in Europe started reporting patients
paper.                                                            with similar features (Despert 1951; Van Krevelen 1952;
    He noted that all his cases exhibited autistic withdrawal,    Creak et al. 1961). However, controversy continued over
a symptom usually seen in schizophrenic patients. Asper-          the definition of the disorder because the name autism was
ger was not aware of Kanner’s work and the paper pub-             ill chosen. It led to confusion with Bleuler’s (1911) use of
lished in 1943. Both Kanner (1943) and Asperger (1944)            the same term to describe the active withdrawal from the
independently used Bleuler’s (1911) earlier term ‘‘autism’’       real world to an inner, presumably fantasy world seen in
to describe the core clinical feature of their disorders. But     schizophrenia (as cited in Wing 1976a). This confusion led
Asperger did not consider his newly discovered disorder a         many clinicians to use terms such as childhood schizo-
form of psychosis. In fact, he appears to have used the term      phrenia, borderline psychosis, symbiotic psychosis, and
‘psychopathy’ to describe a personality disorder, consistent      infantile psychosis as interchangeable diagnoses with
with the meaning of the word in German, since, while              Kanner’s syndrome. Each label had its definition and roots
discussing the paper, he stated that the cases suffered ‘‘with    in a particular view of the nature and causation of autism.
the type of personality disorder presented here.’’                    In an attempt to clarify the confusion, Eisenberg and
    According to Asperger, individuals with Autistic Psy-         Kanner (1956) reduced the essential symptoms to two:
chopathy usually began to speak at approximately the same         extreme self-isolation and preoccupation with the preser-
time as children without this disorder. A full command of         vation of sameness. The peculiar abnormality of language
grammar was acquired sooner or later although some                was considered to be secondary to the disturbance of
children showed difficulty in using pronouns correctly.           human relatedness and, hence, not essential. They also
However, the content of speech was usually abnormal and           expanded the age at onset to the first 2 years of life. Their
pedantic and consisted of lengthy disquisitions on favorite       efforts, however, were sometimes taken as a license to
subjects. Often a word or phrase was repeated over and            ignore age at onset as a necessary diagnostic criterion or to
over in a stereotyped fashion. Other features he described        change the criteria altogether (Rutter 1978). For example,
were impaired two-way social interaction, totally ignoring        Schain and Yannet (1960) omitted preservation of same-
demands of the environment, repetitive and stereotyped            ness from their criteria; Creak et al. (1961) used nine
play, and isolated areas of interests. Asperger observed          diagnostic points to encompass all forms of childhood
these children talking back at teachers, sometimes verbally       psychoses, including Kanner’s (1943) infantile autism,
abusing and hitting other children, and lashing out at            within a single diagnosis (schizophrenic syndrome of
objects. Some of them seemed to gain pleasure from their          childhood); and Ornitz and Ritvo (1968) emphasized dis-
actions with no regard for the feelings of others or the          turbances in perception as a primary symptom that was not
consequences of their actions. Asperger believed that the         included by Kanner.

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   Rutter (1968) critically analyzed the existing empirical        to professionals in the field of PDD in European countries,
evidence and proposed four essential characteristics of            but not in the United States. Wing (1981) suggested that
infantile autism: (1) a lack of social interest and respon-        Asperger’s disorder be considered as a part of the ‘‘autistic
siveness; (2) impaired language, ranging from absence of           continuum.’’ She believed that Asperger’s disorder could
speech to peculiar speech patterns; (3) bizarre motor              be a mild variant of autism. DSM-III-R adopted Wing’s
behavior, ranging from rigid and limited play patterns to          (1981) view of Asperger’s disorder and did not offer any
more complex ritualistic and compulsive behavior; and (4)          specific definition and diagnostic criteria for it.
early onset, before age 30 months. These features were                On the other hand, empirical data published after 1980
present in nearly all children with autism. There were many        could not find any significant differences (except age at
other specific features, but they were unevenly distributed.       onset) between individuals with infantile autism and those
   Infantile Autism in ICD-9-CM and Pervasive Develop-             with childhood-onset PDD. In DSM-III-R, the category
mental Disorders in DSM-III, DSM-III-R—despite Kan-                childhood-onset PDD was eliminated. In addition, it was
ner’s (1943) and Asperger’s (1944/1991) clear elucidation          found to be difficult to differentiate between atypical PDD
of apparently new disorders, both Early Infantile Autism           and residual infantile autism. The DSM-III-R Pervasive
and Autistic Psychopathy were not included in the diag-            Developmental Disorders Work Group therefore decided to
nostic and statistical manual of mental disorders (DSM),           take a combining (lumping) approach and to include only
2nd Edition (APA 1968). Although in DSM-II diagnostic              two subcategories under PDDs: autistic disorder (roughly
information for childhood schizophrenia, there were a              corresponding to infantile autism) and PDD not otherwise
number of symptoms similar to that being described as              specified (PDDNOS). Under such a system, many cases
features of Kanner’s syndrome and Asperger’s disorder              with features of Asperger’s disorder or cases with disin-
(e.g., autistic, atypical and withdrawn behavior’’ (p. 35),        tegrative forms were diagnosed as having either an autistic
they were not equivalent to the diagnostic features of             disorder or a PDDNOS.
Kanner’s syndrome and Asperger’s disorder.                            Although the concept of PDDs was retained in DSM-III-
   Infantile autism first appeared in DSM-III (APA 1980)           R, the diagnostic criteria for autistic disorder were revised
and ICD-9-CM (US Department of Health and Human                    considerably. The DSM-III criteria were descriptive,
Services 1980). Both the diagnostic systems had similar            whereas the menu like scheme of DSM-III-R criteria
definitions and diagnostic criteria for infantile autism.          required the presence of a minimum number of criteria in
However, they differed in the way they conceptualized the          each of the three cardinal areas of deficits. The revised
disorder. In ICD-9-CM, infantile autism was classified as a        criteria were much more concrete, observable, and opera-
subtype of ‘‘psychoses with origin specific to childhood,’’        tional than those in DSM-III. The revised criteria did not
whereas in DSM-III, infantile autism was viewed as a type          require raters to determine subjectively whether a ‘‘perva-
of pervasive developmental disorders (PDDs) (defined as a          sive impairment’’ or a ‘‘gross deficit’’ was present; hence,
group of severe, early developmental disorders character-          clinicians no longer hesitated to use the diagnosis of
ized by delays and distortions in the development of social        autistic disorder in older and higher-functioning autistic
skills, cognition, and communication).                             individuals. DSM-III-R broadened the diagnostic concept
   In DSM-III, the diagnosis of infantile autism required          of autism from DSM-III, allowing for the gradation of
that the features associated with infantile autism (i.e., social   behavior seen in autistic individuals.
problems, communication difficulties, and bizarre behavior)           Autistic disorder and Asperger’s disorder as subtypes of
be present within the first 30 months of life. An atypical         DSM-IV PDDs—after the publication of DSM-III, reports
form, reflecting the findings of Wing and Gould (1979), and        suggested that other developmental disorders such as As-
a residual state subtype, where the individual no longer met       perger’s disorder (Wing 1981), Rett’s disorder (Gillberg
full criteria, but did at one time, were also included in          1987), and disintegrative psychosis (Rutter 1985) should
DSM-III. A childhood-onset PDD subtype was also inclu-             also be considered as separate subgroups of PDDs. How-
ded where symptoms appeared after 30 months but before             ever, the DSM-III-R Work Group on Pervasive Develop-
12 years of age, and did not meet all the symptoms for             mental Disorders did not believe there was sufficient
infantile autism. Thus DSM-III covered the major areas of          evidence for the taxonomic validity of the additional sub-
developmental concern first described by Kanner (1943),            groups of PDDs to justify the establishment of separate
but allowed for later development and for a residual state.        diagnostic categories, preferring instead pervasive devel-
   When DSM-III was published in 1980, Asperger’s dis-             opmental disorder not otherwise specified (PDDNOS). This
order was unknown in the English literature. Hence, DSM-           decision generated the concern that further research on the
III did not include Asperger’s disorder as a subtype of            validity of the subtypes of PDDs would become virtually
PDD. However, when DSM-III-Revised (APA 1987)                      impossible if these disorders were grouped together (Tsai
appeared in 1987, Asperger’s work was fairly well known            1992).

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    DSM-IV (APA 1994) and ICD-10 (WHO 1992) diag-                   Committee accepts the proposed change, the discrete dis-
nostic schemes continue to adopt the term pervasive                 orders that formerly included in PDDs (e.g. autism, As-
developmental disorders and include five subcategories: (1)         perger’s disorder, PDDNOS, and CDD) will be eliminated
autistic disorder, (2) Rett’s disorder, (3) childhood disin-        and all will be absorbed into a single category: Autism
tegrative disorder, (4) Asperger’s disorder, and (5) PDD-           Spectrum disorder (APA 2013). It should be pointed out
NOS (including atypical autism). DSM-IV and ICD-10 also             that DSM-5 ASD is based on a rather small sample size
offer operational diagnostic criteria for all the subtypes of       (i.e., 251 mostly children and adolescent patients from two
PDDs except PDDNOS. The DSM-IV diagnostic criteria                  sites) field trial study (Clarke et al. 2013), and that, so far,
for autistic disorder resemble those of DSM-III-R, but the          no validity study of DSM-5 ASD has been done.
total number of diagnostic criteria has been reduced from               The aim of this paper is to examine the evidence on
16 to 12, and the required minimum number for a diagnosis           which the DSM-5 decision was apparently made. After
of autistic disorder also has been reduced from 8 to 6.             underscoring the main points of the reviews on the the
These changes were made to facilitate the use of the cri-           subtypes (based on which it was apparently decided to
teria by clinicians while the diagnostic validity and reli-         merge them), it critically examines the studies comparing
ability are maintained at a high level.                             (1) Asperger’s disorder with high functioning Autism; (2)
    The concept of PDDs in DSM-IV adopts a ‘‘splitters’’            Asperger’s disorder with low functioning Autism; and (3)
approach. It supports the taxonomic validity of each sub-           Autistic disorder with PDDNOS.
type and aims to facilitate research in the sub-classification
of these disorders. Although the DSM-IV diagnostic cri-
teria for PDDs are based on a well designed multisite field         Methods
trial study in which 977 patients participated (Volkmar
et al. 1994), it is expected that these criteria will not satisfy   A comprehensive literature search, limited to English-lan-
everyone and they will be revised when improved under-              guage journals, was conducted to locate review studies
standing and further knowledge are gained to support the            published between 1994 and 2013 that examined differ-
taxonomic validity of each subtypes of the newer edition of         ences and/or similarities between AsD and AD. Using the
DSM.                                                                keywords: autism, high-functioning autism, Asperger’s
    During the two decades since the publication of the             disorder, Asperger’s syndrome, pervasive developmental
ICD-10 (1992) and the DSM IV (1994), both clinicians and            disorder, PDDNOS, PDD NOS, and autism spectrum dis-
researchers, in various settings, have used the subtypes of         order, the following major databases were examined:
PDD to describe children and adults with a range of social          PubMed, MEDLINE, PsycINFO, and ERIC. Reference
and other deficits. More than 500 studies of Asperger dis-          lists from relevant articles (e.g., literature reviews), and
order alone (including about 150 comparative studies of             recent editions of key journals (e.g., Journal of Child
AsD and High Function Autism) have been published.                  Psychology and Psychiatry, Autism, Journal of Autism and
However, the debate has continued between the ‘splitters’           Developmental Disorders, Research of Autism Spectrum
and the ‘lumpers,’ with the latter maintaining that autism          Disorder) were also used to identify the relevant articles.
and AsD lie on a ‘‘continuum’’ with AsD at the less                 The literature search of the databases and reference lists
impaired end.                                                       was extended to the end of February 2013.
    DSM-5 ASD as a single category—in 2007, the Amer-                   Two approaches were taken to assess the identified
ican Psychiatric Association formed a Work Group on                 papers: (1) Review and analyze previous review papers that
Neurodevelopmental Disorders to review DSM-IV PDDs                  focused on the comparison between AD and AsD, (2)
and to develop a new definition and diagnostic criteria or to       Review and analyze previous studies that compared low
replace the PDDs in DSM-5. After spending nearly 2,500 h            functioning AD (LFA) and AsD, and that compared AD
at in-person meetings and 3,500 h on teleconferences                and PDDNOS.
(Swedo et al. 2012), the Work Group concluded that there
was sufficient evidence to replace the term ‘‘PDDs’’ with
‘‘Autism Spectrum disorder (ASD)’’ and to subsume As-               Results
perger’s disorder, childhood disintegrative disorder (CDD),
and PDDNOS into the overarching category of ASD. The                The literature search identified nine review studies. Four
proposal asserted that symptoms of these three disorders            review studies concluded that there was ‘‘no difference’’
represented a continuum from mild to severe of autism,              between AsD and HFA; 2 reviews concluded that AsD was
rather than a simple yes or no diagnosis of a specific dis-         a ‘‘distinct disorder’’; and 4 reviews concluded that it was
order. The Work Group also proposed to remove Rett’s                premature to exclude AsD from the proposed DSM-5 ASD
disorder from DSM-50 s ASD category. The APA DSM-5                  (See Table 1). Three groups of investigators (Kaland 2011;

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Table 1 Review studies comparing between AD and AsD
Author(s) (year)         Covered     Number     Variables studied                                                   Conclusion
                         period      of
                                     studies
                                     reviewed

Myer and Minshew         1989–2000   14         IQ, cognition, language, motor skills, TOM, creativity, false-      No difference between AD
 (2002)                                           belief, recognizing mental state clinical characteristics,         and AsD
Howlin (2003)            1989–2001   26           neuropsychological & language profiles, obstetric history and     No difference between AD
                                                  motor abnormalities, behavioral and psychiatric disturbance        and AsD
Macintosh and            1989–2003   41         IQ, cognitive profiles, language, echolalia, social cognition,      No difference between AD
 Dissanayake (2004)                               social difficulty, global processing, TOM, visual-spatial          and AsD
                                                  skills, spatial cognition, motor function, movement pre-
                                                  paration, diagnosis, comorbidities, obstetric history, genetic,
                                                  epidemiology
Sanders (2009)           2000–2008   16         IQ profiles, verbal ability, voice profiles, language               No difference between AD
                                                  development, cognitive & symptom profiles, sensory-motor           and AsD
                                                  & cognitive functions self-presentational display rules, social
                                                  interactions, social skills & problem behaviors, social phobia,
                                                  diagnosis, follow-up and outcomes
Matson and Wilkins       1989–2007   22         Onset/developmental, social interaction, communication,             AsD is a ‘‘distinct disorder’’
 (2008)                                          restricted or repetitive behaviors & interests, sensory-motor
                                                 function, intellectual/adaptive functioning, psychopathology,
                                                 general
Kugler (1998)            1987–1996   18         Social skills, language, IQ profiles, cognition, diagnosis, motor   AsD is a ‘‘distinct disorder’’
                                                 function
Rinehart et al. (2002)   1996–2002   22         Neurocognitive, pedantic speech, neuropsychology, TOM,              Premature to exclude AsD
                                                 embedded figure test, the strange stories recognition of faux,      from the DSM-5 ASD
                                                 belief, behavior & emotion, global processing, lateralization,
                                                 visual illusion, shifting attention, neuropsych profiles
                                                 movement, motor impairment, genetic, epidemiology,
                                                 outcome
Witwer and Lecavalier    1994–2006   22         IQ profiles, neuropsychological profiles, language measures,        Premature to exclude AsD
 (2008)                                           pedantic speech, sensory–motor & cognitive function,               from the DSM-5 ASD
                                                  executive function, repetitive & stereotyped behavior and
                                                  social disturbance, emotional/behavioral symptoms,
                                                  depression and anxiety, anxiety & psychotic symptoms,
                                                  psychiatric symptoms, early history, diagnosis, sex rates,
                                                  follow-up and outcomes
Kaland (2011)            1996–2010   11         Social behavior, pedantic speech, language development, IQ          Premature to exclude AsD
                                                 profiles, cognitive and symptom profile, cortical inhibition,       from the DSM-5 ASD
                                                 cortical gyrification, diagnosis

Kugler 1998; Witwer and Lecavalier 2008) called for more                showed ‘‘significant or near significant level of differ-
studies to revise and refine the external validity of Asperger          ences’’ on many clinical variables between AsD and HFA
disorder.                                                               as studies finding ‘‘no difference’’ between the two
    The first author recently completed a comprehensive                 subtypes.
review of this issue (Tsai 2013). The review identified                    Comparative studies between Asperger’s disorder and
128 publications of comparative studies of AsD and HFA                  Low Functioning Autism (LFA)—although a recent study
(from 1995 to 2012). Based on more than 90 clinical                     by Charman et al. (2011) found 53 % of 81 children with
variables, 94 publications concluded that there were sta-               ‘‘childhood autism’’ had ‘‘intellectual disability defined by
tistically significant or near significant level of quantita-           an IQ \70, the long-established view was that up to 75 %
tive and/or qualitative differences between AsD and AD/                 of individuals with autism had intellectual disability severe
HFA groups; 4 publications found both similarities and                  enough to cause impairment in everyday functioning
differences between the two groups; and 30 publications                 (Volkmar et al. 2004; Tsatsanis 2005). However, few
concluded with no differences between the two groups.                   studies have compared Asperger’s disorder with autism with
Thus, the review of studies comparing AsD and HFA                       intellectual disability/mental retardation (low functioning
showed that about three times as many studies (94 vs 30)                autism, LFA).

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    The literature search identified 12 studies that compared    Butler 1998), Social skills (Njardvik et al. 1999), prenatal,
individuals with LFA to individuals with AsD. Six (Ced-          perinatal, and neonatal factors (Juul-Dam et al. 2001),
erlund et al. 2008; de Bruin et al. 2006; Ghanizadeh 2011;       psychiatric symptoms (Kenneth et al. 2004), clinical
Mori et al. 2009; Ramberg et al. 1996; Toal et al. 2010) of      characteristics (Walker et al. 2004), presentation of anxiety
the 12 studies combined both LFA and HFA individuals             (Weisbrot et al. 2005), behavioral and emotional func-
into a single ‘‘Autism’’ group. The other six studies (Bal-      tioning (Pearson et al. 2006), developmental/intellectual
coni et al. 2012; Larsen and Mouridsen 1997; Lotspeich           changes (Takeda et al. 2007), shape mapping of the hip-
et al. 2004; Nordahl et al. 2007; Schumann et al. 2004;          pocampus (Dager et al. 2007), chemical metabolites in the
Scott et al. 2009) had a separate LFA group, which was           amygdala-hippocampus region (Endo et al. 2007),
compared to the AsD group. However, four (Lotspeich              magnetoencephalographic pattern of epileptiform activity
et al. 2004; Nordahl et al. 2007; Scott et al. 2009; Schu-       (Muñnoz-Yunta et al. 2008), characteristics of challenging
mann et al. 2004) of the six studies were carried out by the     behaviours (Matson and Rivet 2008), effects of intellectual
same group of investigators. Nonetheless, five out of the        functioning on the range of core symptoms (Matson et al.
six studies (Balconi et al. 2012; Larsen and Mouridsen           2008), social skills (Wilkins and Matson 2009), adaptive
1997; Lotspeich et al. 2004; Nordahl et al. 2007; Schumann       independent living skills (Matson et al. 2009a), brain
et al. 2004) reported significant or near significant differ-    morphometry volume (Hallahan et al. 2009), patterns of
ences between LFA and AsD groups.                                growth in adaptive social abilities (Anderson et al. 2009),
    To accept that AsD lies on a ‘‘continuum’’ with AD, it       social and communication behavior (Fodstad et al. 2009),
would be necessary to show that AsD is similar to the            stereotypies and repetitive/restrictive behaviours (Matson
lower functioning end of AD as well. Overall, the number         et al. 2009b), one carbon metabolism disturbances and the
of studies comparing LFA to AsD is small. If there is any        C677T MTHFR gene polymorphism (Pasca et al. 2009),
direction one could predict with a larger number of studies,     developmental milestones (Matson et al. 2010), race and
it would be that LFA is quite differen from AsD.                 challenging behaviors (Horovitz et al. 2011), independent
    Comparative studies between PDDNOS and AD—                   measures of core PDD symptomatology (Mandy et al.
although PDDNOS tends to be more commonly diagnosed              2011), parent-reported behavior problem (Snow and Le-
than AD, there are very few studies on the predictive            cavalier 2011), meta-analysis of stability (Rondeau et al.
validity and stability of this disorder. During the last dec-    2011), language comprehension (Kjellmer et al. 2012), pre-
ade, several studies have questioned the adequacy of the         and perinatal risk factor (Visser et al. 2012), and preva-
current PDDNOS category and the literature so far has            lence of SHANK3 variants (Boccuto et al. 2013).
been unable to clearly differentiate children with PDDNOS           Overall, although the literature appears to suggest that
from children with AD (Allen et al. 2001; Volkmar et al.         PDDNOS can be separated from AD, and, therefore, does
2009; Walker et al. 2004).                                       not seem to lie on a ‘‘continuum’’ with that disorder. More
    The present literature search identified 37 studies that     systematic research is needed to settle the issue. Till then,
compared PDDNOS with Autism/Autistic disorder. The               PDDNOS (or replaced by other diagnostic term) should be
total subjects included in the 37 studies were 2,506 with        regarded as a separate category to facilitate ongoing
PDDNOS and 3,462 with Autism/autistic disorder. Out of           research.
this, 9 studies (which included 470 subjects with PDDNOS
and 872 subjects with Autism) concluded that there was no
difference between PDDNOS and Autism groups on vari-             Discussion
ous clinical variables: WISC-R subtests (de Bruin et al.
2006), long-term prognosis (Mordre et al. 2012), executive       To facilitate the study of diagnostic validity of psychiatric
functioning (Verté et al. 2006a), cognitive profiles (Kanai     disorders, Robins and Guze (1970) proposed a process that
et al. 2012), utility of Children’s Communication Check-         included the following phases: clinical description, labo-
list(Verté et al. 2006b), birth defects (Dawson et al. 2009),   ratory studies, follow-up studies, and family studies. The
and copper and zinc plasma concentration and the efficacy        evolution of the American Psychiatric Association’s
of zinc therapy (Russo and DeVito 2011), adaptive inde-          Diagnostic and Statistical Manual (DSM) has closely fol-
pendent living skills (Matson et al. 2009a, b), verbal and       lowed such a process. Initially the DSM was developed for
adaptive skills (Allen et al. 2001).                             psychiatrists who were interested in describing and
    Twenty-eight studies (which included 2,036 subjects          understanding the frequency with which mental illnesses
with PDDNOS and 2,590 subjects with Autism) concluded            developed in our society. In 1980, the DSM-III moved
that there were some quantitative and qualitative differ-        from a descriptive or conceptual approach to an opera-
ences between PDDNOS and Autism groups on the fol-               tionalized, criteria-defining approach to enable clinicians to
lowing clinical variables: clumsiness (Ghaziuddin and            make diagnoses based on whether a patient’s symptoms

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J Autism Dev Disord

matched the diagnostic criteria. The DSM-III also intended         of the subtypes of ASD) will be put on hold for many years
to establish a higher degree of diagnostic consistency or          to come.
reliability within the psychiatric community. The expec-              It has been reported that the DSM-5 Neurodevelop-
tation of DSM-III and subsequent DSM-III-R, DSM-IV,                mental Workgroup’s rationale for subsuming Asperger’s
and DSM-IV-TR (APA 2000) was that DSM based                        disorder into ASD was partly based on the finding by Lord
research would identify the underlying etiologies of the           et al. (2012) that ‘‘the best predictor of which autism
disorders included in the manuals, which would allow               spectrum diagnosis a person received (Asperger disorder,
greater refinement of the criteria and ultimately their val-       PDD-NOS, or autistic disorder) was which clinic the
idation by biological measures which in turn would lead to         individuals went to, rather than any characteristic of the
specific treatments and even prevention or cures (Tsai             individual’’ (see Happé 2011). While we agree that the
2012). However, from DSM-III to DSM-IV-TR, the pro-                diagnosis of autism or Asperger’s disorder (indeed, of any
gress of research has not led to the definitive identification     psychiatric disorder) depends on where and by whom it is
of etiologies or the validation of proven biological mea-          made, this observation alone does not fully explain the
sures or substrates to define mental disorders. This, by the       main findings reported in our paper.
way, is not unique to research in the field of autism; in fact,       After an initial period of confusion, clinicians and
the scientific foundation of classification of almost all          researchers have learned to use the DSM-IV and ICD 10
psychiatric disorders is rather weak (see Uher and Rutter          criteria of PDD/ASD and its subtypes based on the
2012). For Instance, the fact that the distinction between         descriptions of Kanner and Asperger. This is reflected by
the various subtypes of mood disorders is not clear, does          the fact that more than 3,300 cases with AsD and more than
not justify the creation of a unitary category of mood             3,700 cases with HFA/AD have been identified and
spectrum disorder. If autism is a psychiatric disorder, there      enrolled in the comparison studies from 1994 to 2012 (Tsai
is no reason why its classification should be held to a            2013). In addition, over 2,500 subjects with PDDNOS have
different standard. After all, validity and reliability alone      participated in the studies cited earlier. This, in itself,
should not define the rationale for classification; utility is     points to the existence of the face validity of these disor-
also important (Ghaziuddin 2010). As others have also              ders based on DSM-IV and ICD-10 criteria. Neither the
argued (Leventhal 2012; Ritvo 2012; Wing et al. 2011),             lack of hard scientific evidence for the existence of a single
there is a real risk that eliminating the subtypes of PDDs         category of ASD nor the absence of clinical consensus for
and creating a single ASD will have an impact on services          combining the subgroups, seemed to have deterred the
and may actually result in some patients being denied              DSM-5 from reverting to the DSM-III-R’s approach to
services.                                                          lump the categories together. As opposed to this, the ICD-
   A related issue is the use of the diagnostic criteria. In the   11, due to be published in 2015, will most likely continue
absence of a biological test of autism, there is a belief that     to have the subtypes of Autism, Asperger syndrome (or
structured instruments and observation schedules might be          social reciprocity disorder), disintegrative disorder, and
sufficient. Over-reliance on these instruments can some-           Rett syndrome (WHO 2012). This, we believe, would have
times lead to circular arguments and clinical fallacies. In        been the step forward that the DSM-5 ASD unfortunately
this regard, two points are important. First, rating scales        missed.
cannot replace diagnostic criteria (Rutter 2011); and, sec-
ond, the gold standard of clinical diagnosis of autism
remains clinical (Charman and Gotham 2013).
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