Review
Structural magnetic resonance imaging data do not help support DSM-5 autism spectrum disorder category

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Abstract

This systematic review aims to determine whether or not structural magnetic resonance imaging (sMRI) data support the DSM-5 proposal of an autism spectrum disorder (ASD) diagnostic category, and whether or not classical DSM-IV autistic disorder (AD) and Asperger syndrome (AS) categories should be subsumed into it. The most replicated sMRI findings in patients with ASD compared with healthy controls are increased total brain volume in early childhood and decreased corpus callosum volume. Regarding the notion of a spectrum, some studies support that AS and AD are similar but “quantitatively different” diagnostic categories, whereas others support that they are “qualitatively different” entities with specific brain structural abnormalities. It seems that there are still not enough arguments from sMRI data for or against subsuming DSM-IV categories under a single ASD category.

Highlights

► We conducted a systematic review of studies providing sMRI data in autism spectrum disorders – ASD. ► Patients with ASD showed increased total brain volume in early childhood compared with controls. ► Some data support that Asperger syndrome and Autistic disorder are “quantitatively different”. ► Some data support they are “qualitatively different” (with specific brain abnormalities). ► There are still not enough arguments for/against subsuming DSM-IV categories under ASD category.

Introduction

In 1979, Wing launched the concept of the autistic continuum or spectrum (Wing & Gould, 1979) and, nine years later, Allen coined the term autism spectrum disorders (Allen, 1988). However, controversy still surrounds Wing's original concept of a broad autistic phenotype. In fact, clinicians and researchers have used the term autism spectrum disorders to include autistic disorder (AD) (including high functioning autism – HFA – and low functioning autism – LFA), Asperger syndrome (AS), and pervasive developmental disorder not otherwise specified (PDD NOS) (Levy, Mandell, & Schultz, 2009), where the term “spectrum” reflects the variability in symptom severity among patients. In this context, there is a proposal for the forthcoming DSM-5 diagnostic classification to create the broad diagnostic category of autism spectrum disorder (ASD) (see www.dsm5.org). Nevertheless, there are still unanswered questions about the ASD construct, which have led to the current debate on how ASD should best be conceptualized in DSM-5 (Frazier et al., 2012, Happe, 2011, Mandy et al., 2012, Mattila et al., 2011, Pina-Camacho et al., 2012, Tanguay, 2011). One of these questions is whether ASD constitutes a well defined biological entity compared with the earlier pervasive developmental disorders, and whether classic DSM-IV categories – and especially AS – should be subsumed into this broader category.

Over the past few decades, magnetic resonance imaging (MRI), a non-invasive in vivo technique, has allowed access to the anatomy and physiology of the developing brain and has contributed to our understanding of neurodevelopment in health and illness (Giedd & Rapoport, 2010). In the late eighties, researchers started using structural MRI (sMRI) to examine pathological changes in the brain structure of pediatric and psychiatric patients (Mana et al., 2010, Potts et al., 1993), including those with autism. Widely used sMRI techniques are summarized in Table 1. Initially, studies measured volume by totaling the amount of voxels in manually predefined regions of interest (ROIs). These methods were followed up by voxel-based approaches such as voxel-based morphometry (VBM) (Whitwell, 2009), which allows whole brain exploration of structural differences and thus does not depend on manually predefined regions. More recently, with the advent of improved image acquisition (e.g., higher field strength, higher isotropic voxel resolution, and improved gray-white matter contrast), additional morphometric measures that focus on the thickness, surface area, and curvature of the cortex have emerged. Furthermore, multivariate statistical analysis frameworks have been developed that aim to classify subjects as patients or controls based on large morphometric datasets (Chung et al., 2005, Chung et al., 2007, Chung et al., 2009, Ecker et al., 2010a, Fischl and Dale, 2000, Gorczowski et al., 2010, Singh et al., 2008, Uddin et al., 2011, Vatta and Di Salle, 2011).

There has been a steady rise in the number of sMRI publications both in the forthcoming ASD category and in the classic DSM-IV categories, mainly in AD and AS (Mana et al., 2010). In these studies, the authors have tried to define the neurological underpinnings of these diagnostic entities and to relate brain structural abnormalities with associated behavioral and clinical features. However, few studies have tried to summarize the findings of previous sMRI reports in order to find neuroanatomic evidence for the new ASD diagnostic category (Chen et al., 2011, Stigler et al., 2011, Verhoeven et al., 2010). The objective of this review is to assess whether or not reported sMRI findings support the proposal of subsuming DSM-IV categories under this new ASD category based on specific neuroanatomical substrates.

Section snippets

Methods

We conducted a systematic PubMed search on structural MRI studies of ASD published in English between January 1990 and February 2012. The following database search strategy was used: ‘(“autism spectrum disorders” [All Fields] OR “Asperger syndrome” [All Fields] OR “Asperger's syndrome” [All Fields] OR “Autistic disorder” [All Fields]) AND (“Magnetic resonance imaging” [All Fields]) NOT pubstatus ahead of print’. After excluding in-press papers, as not all of them were available in full text,

Results

Most studies included in this review compare patients with ASD (without distinction between DSM-IV subcategories) or HFA with healthy controls (HC). We found eight studies comparing patients with HFA and AS (Haznedar et al., 2006, Jou et al., 2010, Kwon et al., 2004, McAlonan et al., 2008, McAlonan et al., 2009, Toal et al., 2010, Via et al., 2011, Yu et al., 2011), four studies comparing patients with LFA, HFA, AS, and HC (Lotspeich et al., 2004, Nordahl et al., 2007, Scott et al., 2009,

Discussion

Despite of the extensive literature on the use of sMRI in patients with ASD, there are few consistent structural findings (Chen et al., 2011). Moreover, these findings do not always correlate with clinical, neuropathological, or neuropsychological features of the disorder (Eliez and Reiss, 2000, Griebling et al., 2010, Hardan et al., 2006a, Hardan et al., 2006b, Lord et al., 2000). Thus, it seems that sMRI data currently do not help resolve the DSM-IV versus DSM-5 controversy. In other words,

Conclusions

From the point of view of psychiatric taxonomy, Volkmar has already argued that the inclusion of a specific diagnosis, such as AS, within a nosological classification, “is only important if the use of the concept can be supported on the basis of some external validating factor” (Volkmar et al., 2000). For example, specific clinical features have been used as arguments to justify maintaining AS in DSM-5 (Ghaziuddin, 2010), such as the presence of ego-dystonic lack of reciprocal social

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgments

Supported by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, CIBERSAM, the Autonomous Community of Madrid, I + D Biomedicine, S2010/BMD-2422 AGES (Madrid, Spain), the ERA-NET NEURON (Network of European Funding for Neuroscience Research), and Fundación Alicia Koplowitz and Fundación Mutua Madrileña.

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