Can Asperger syndrome be distinguished from autism? An anatomic likelihood meta-analysis of MRI studies. J Psychiatry Neurosci

Department of Psychiatry, The University of Hong Kong, Pokfulam, Hong Kong.
Journal of psychiatry & neuroscience: JPN (Impact Factor: 5.86). 03/2011; 36(6):412-21. DOI: 10.1503/jpn.100138
Source: PubMed


The question of whether Asperger syndrome can be distinguished from autism has attracted much debate and may even incur delay in diagnosis and intervention. Accordingly, there has been a proposal for Asperger syndrome to be subsumed under autism in the forthcoming Diagnostic and Statistical Manual of Mental Disorders, fifth edition, in 2013. One approach to resolve this question has been to adopt the criterion of absence of clinically significant language or cognitive delay--essentially, the "absence of language delay." To our knowledge, this is the first meta-analysis of magnetic resonance imaging (MRI) studies of people with autism to compare absence with presence of language delay. It capitalizes on the voxel-based morphometry (VBM) approach to systematically explore the whole brain for anatomic correlates of delay and no delay in language acquisition in people with autism spectrum disorders.
We conducted a systematic search for VBM MRI studies of grey matter volume in people with autism. Studies with a majority (at least 70%) of participants with autism diagnoses and a history of language delay were assigned to the autism group (n = 151, control n = 190). Those with a majority (at least 70%) of individuals with autism diagnoses and no language delay were assigned to the Asperger syndrome group (n = 149, control n = 214). We entered study coordinates into anatomic likelihood estimation meta-analysis software with sampling size weighting to compare grey matter summary maps driven by Asperger syndrome or autism.
The summary autism grey matter map showed lower volumes in the cerebellum, right uncus, dorsal hippocampus and middle temporal gyrus compared with controls; grey matter volumes were greater in the bilateral caudate, prefrontal lobe and ventral temporal lobe. The summary Asperger syndrome map indicated lower grey matter volumes in the bilateral amygdala/hippocampal gyrus and prefrontal lobe, left occipital gyrus, right cerebellum, putamen and precuneus compared with controls; grey matter volumes were greater in more limited regions, including the bilateral inferior parietal lobule and the left fusiform gyrus. Both Asperger syndrome and autism studies reported volume increase in clusters in the ventral temporal lobe of the left hemisphere.
We assigned studies to autism and Asperger syndrome groups for separate analyses of the data and did not carry out a direct statistical group comparison. In addition, studies available for analysis did not capture the entire spectrum, therefore we cannot be certain that our findings apply to a wider population than that sampled.
Whereas grey matter differences in people with Asperger syndrome compared with controls are sparser than those reported in studies of people with autism, the distribution and direction of differences in each category are distinctive.

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    • "Genetic studies have likewise produced little support for a discrimination between AS and HFA, although this must be tempered by growing evidence of a common genetic susceptibility shared by neurodevelopmental disorders in general, rather than a specific genetic etiology for each disorder (Lichtenstein et al., 2010). Structural MRI studies comparing AS and HFA have produced contradictory results, with two recent meta-analyses and a recent systematic review reaching three different conclusions (Via et al., 2011;Yu et al., 2011;Pina-Camacho et al., 2013). The most consistent positive findings come from studies that differentiated AS from HFA based on language acquisition history: compared to AS and typical controls, HFA subjects have lower gray matter and white matter volumes, increased gyrification, and abnormal cortical folding in inferior frontal areas (including the pars opercularis;Nordahl et al., 2007;McAlonan et al., 2008McAlonan et al., , 2009Jou et al., 2010); increased gray matter in supramarginal, superior temporal and inferior parietal gyri bilaterally (McAlonan et al., 2008;Jou et al., 2010;Toal et al., 2010), and decreased volume of the cerebellar vermis and posterolateral lobule (Scott et al., 2009;Hodge et al., 2010). "
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    ABSTRACT: First described in 1944 by Hans Asperger, it was not before 1994 that Asperger Syndrome (AS) was included in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders, only to disappear in the Manual’s 5th edition in 2013. During its brief existence as a diagnostic entity, AS aroused immense interest and controversy. Similar to patients with autism, AS patients show deficits in social interaction, inappropriate communication skills, and interest restriction, but also display a rich variety of subtle clinical characteristics that for many distinguish AS from autism. However, difficulties operationalising diagnostic criteria and differentiating AS from autism ultimately led to its merging into the unifying category of Autistic Spectrum Disorders. Here we briefly review the short history of this fascinating condition.
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    • "Structural MRI studies have described hypoplasia of the posterior vermis in ASD (Carper and Courchesne, 2000; Courchesne et al., 1988, 1994, 2011; Murakami et al., 1989), and meta-analyses of voxel-based morphometry (VBM) studies have reported consistent gray matter (GM) decreases in right Crus I, lobule VIII, and lobule IX (Duerden et al., 2012; Stoodley, 2014; Yu et al., 2011). Decreased GM is less commonly reported in regions such as left Crus I, and sometimes overall increased cerebellar GM is noted (Duerden et al., 2012; Yu et al., 2011). Functional MRI studies have revealed reduced activation in the cerebellum in ASD during social, language, and motor tasks. "
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    ABSTRACT: Neuroanatomical differences in the cerebellum are among the most consistent findings in autism spectrum disorder (ASD), but little is known about the relationship between cerebellar dysfunction and core ASD symptoms. The newly-emerging existence of cerebellar sensorimotor and cognitive subregions provides a new framework for interpreting the functional significance of cerebellar findings in ASD. Here we use two complementary analyses — whole-brain voxel-based morphometry (VBM) and the SUIT cerebellar atlas — to investigate cerebellar regional gray matter (GM) and volumetric lobular measurements in 35 children with ASD and 35 typically-developing (TD) children (mean age 10.4 ± 1.6 years; range 8-13 years). To examine the relationships between cerebellar structure and core ASD symptoms, correlations were calculated between scores on the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview (ADI) and the VBM and volumetric data. Both VBM and the SUIT analyses revealed reduced GM in ASD children in cerebellar lobule VII (Crus I/II). The degree of regional and lobular gray matter reductions in different cerebellar subregions correlated with the severity of symptoms in social interaction, communication, and repetitive behaviors. Structural differences and behavioral correlations converged on cerebellar Crus I/II, a region which shows structural and functional connectivity with fronto-parietal and default mode networks. These results emphasize the importance of the location within the cerebellum to the potential functional impact of structural differences in ASD, and suggest that GM differences in cerebellar right Crus I/II are associated with the core ASD profile.
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    • "Looking at subcortical structures, the caudate has been shown to be enlarged in ASD, across whole brain volumetric meta-analyses (81–83), and in targeted ROI analysis, even after controlling for confounding medication administration (84). Volume loss in the putamen has been shown across whole brain meta-analyses in adults with ASD (81, 83, 85), but enlargement of the putamen has also been observed in younger populations (86). In the amygdala, volume losses emerge across whole brain meta-analytic approaches (83, 85, 87), but volume gains are noted in younger patient groups as well (88). "
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    ABSTRACT: Background: Autism spectrum disorder (ASD) and childhood onset schizophrenia (COS) are pediatric neurodevelopmental disorders associated with significant morbidity. Both conditions are thought to share an underlying genetic architecture. A comparison of neuroimaging findings across ASD and COS with a focus on altered neurodevelopmental trajectories can shed light on potential clinical biomarkers and may highlight an underlying etiopathogenesis. Methods: A comprehensive review of the medical literature was conducted to summarize neuroimaging data with respect to both conditions in terms of structural imaging (including volumetric analysis, cortical thickness and morphology, and region of interest studies), white matter analysis (include volumetric analysis and diffusion tensor imaging) and functional connectivity. Results: In ASD, a pattern of early brain overgrowth in the first few years of life is followed by dysmaturation in adolescence. Functional analyses have suggested impaired long-range connectivity as well as increased local and/or subcortical connectivity in this condition. In COS, deficits in cerebral volume, cortical thickness, and white matter maturation seem most pronounced in childhood and adolescence, and may level off in adulthood. Deficits in local connectivity, with increased long-range connectivity have been proposed, in keeping with exaggerated cortical thinning. Conclusion: The neuroimaging literature supports a neurodevelopmental origin of both ASD and COS and provides evidence for dynamic changes in both conditions that vary across space and time in the developing brain. Looking forward, imaging studies which capture the early post natal period, which are longitudinal and prospective, and which maximize the signal to noise ratio across heterogeneous conditions will be required to translate research findings into a clinical environment.
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