Article

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

ABSTRACT

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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    • "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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    • "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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