Autisms are a highly heterogeneous set of disorders with wide variations in symptom severity, intellectual level, and functional disability.1
The importance of accurately identifying individuals with autism has never been greater, particularly given the growing prevalence,2
considerable family and societal costs,3
and recognized importance of early diagnosis and intervention. DSM-5 Field Trials have recently begun evaluating new diagnostic criteria that contain several important modifications relative to DSM-IV-TR.4, 5
The most remarkable change was combining specific DSM-IV-TR diagnoses into a single broad Autism Spectrum Disorder (ASD). This proposed change has generated considerable apprehension from patients and their families, who are concerned that individuals diagnosed with Asperger’s disorder will be orphaned or receive inappropriate service provision.6
Yet, to date, there is little evidence that Asperger’s disorder is qualitatively distinct from other autism diagnoses at the symptom level or that the new criteria will under-identify high functioning ASD.7
The present study evaluates an important aspect of this controversy - symptom continuity between individuals with Asperger’s disorder and other ASD cases - by explicitly testing conflicting views of the nature of autism symptom structure.
The first viewpoint proposes that autism symptoms are best represented dimensionally, with differences between typical and ASD symptom levels being a matter of degree (ie. no distinct ASD category is present).8
This perspective is supported by the observations from population and family studies of a broad distribution of observed
autism symptoms in the population,9
elevated levels of autism traits in siblings and other family members of affected cases,10, 11
and shifting toward greater autism symptoms in children whose parents both show sub-threshold autism traits.12
Also compelling are possible genetic heterogeneity of symptom domains13, 14
and the substantial variability of autism symptoms among identical twins.15, 16
This evidence points toward the need to include a dimensional conceptualization of autism symptoms in its diagnosis.
The second viewpoint is that autism symptoms represent a category, with qualitative differences in symptom levels between ASD-affected and unaffected individuals.17–19
Two recent studies supported the categorical conceptualization of autism, identifying a latent
symptom category parsing ASD and non-ASD cases.20, 21
Longitudinal studies of early (age 2) and later (ages 3–9) diagnoses also support the notion of a single, distinct ASD category.22, 23
These studies found strong stability of the broad ASD distinction, while substantial shifting occurred within specific DSM-IV diagnoses. Similarly, most studies of ASD symptoms and cognitive processes have identified only quantitative distinctions among DSM-IV disorders.7, 24, 25
It is possible that both viewpoints are correct and that categorical and dimensional aspects of autism symptoms should be considered in the conceptualization of ASD. In fact, in addition to an ASD category, DSM-5 also identifies two symptom dimensions - Social Communication and Interaction (SCI) and Restricted, Repetitive Behavior (RRB) that collapse the three DSM-IV-TR domains. Thus, DSM-5 presents a complex model with a single ASD category superimposed on two primary symptom dimensions. The present study investigated the plausibility of the DSM-5 conceptualization of autism symptoms by comparing categorical, dimensional, and hybrid latent variable models (Aim 1).26–28
Based on the DSM-5 model of ASD, we hypothesized that autism symptoms would be most parsimoniously represented by hybrid models specifying a categorical distinction (ASD vs. non-ASD) and two dimensions (SCI and RRB).
The distinction between dimensional, categorical, and hybrid models has relevance beyond diagnostic conceptualization - impacting the clinical assessment approach. If autism symptoms are best represented by a latent category, the prevalence of ASD, sibling recurrence rates, and the most useful diagnostic criteria are defined. In this case, an evidence-based medicine approach to clinical assessment that includes the generation of post-test probabilities of diagnosis is indicated.29
Under this scenario, instruments should be used to optimize classification rather than only grading autism symptom severity. In contrast, if only a latent continuum is needed to describe autism symptoms, additional research is needed to link the continuum to clinically relevant outcomes, such as functional deficits, prior to setting a diagnostic threshold. If hybrid models are supported, integration of the above approaches will be needed to most accurately characterize the presence vs. absence of ASD and to grade symptom severity.
Identifying the latent structure of autism also facilitates the design and analysis of future research.30, 31
If the latent structure of autism is categorical, then traditional group comparison research is optimized if individuals are accurately sorted into ASD and non-ASD groups. Alternatively, if a continuum is identified, research designs would be more efficient if autism symptoms are measured as quantitative traits and regression or latent factor approaches are implemented rather than group comparisons. A latent ASD category might also facilitate future neurobiological and genomic research. For example, a latent category may support developmental models postulating distinct divergence in brain structure and function.32, 33
An ASD category could also favor molecular models emphasizing the primacy of strong individual genomic effects,34–37
such as private mutations or copy number variations involving genes crucial for early brain maturation,38
although this is less certain because of the potential for genetic threshold effects. In contrast, strictly dimensional representations of autism would suggest graded alterations in brain development, overlapping typical brain trajectories, and a primary role for polygenic common variation and other additive genomic and environmental effects.37, 39, 40
Finally, hybrid models of ASD symptoms may imply a more complex pattern, such as combinations of rare and common variation as well as environmental effects contributing to the ASD phenotype.27, 41
Comparing models of autism symptom structure will be crucial for advancing diagnostic criteria, clinical assessment, and future molecular and neurobiological research.
The present study also evaluated specific changes in the proposed DSM-5 algorithm examined in Phase I trials (Aim 2). These changes include: 1) collapsing three domains into two - Social Communication and Interaction (SCI) and Restricted, Repetitive Behavior (RRB), 2) requiring all SCI criteria and at least 2 of 4 RRB criteria to be met, 3) necessitating at least 2 specific symptoms present per criterion, 4) providing a separate RRB criterion evaluating sensory sensitivities and unusual sensory interests, and 5) adding subtle behavioral manifestations of high functioning ASD. Thus, as a secondary aim, we explored the relative classification accuracy of DSM-IV-TR and proposed DSM-5 criteria to inform future diagnostic revisions in Phase II trials and to provide guidance to evaluating clinicians.