A voxel-based morphometry comparison of regional gray matter between Fragile X Syndrome and autism

Department of Psychiatry, University of Colorado at Denver, Denver, CO, 80045, USA.
Psychiatry Research (Impact Factor: 2.47). 11/2009; 174(2):138-45. DOI: 10.1016/j.pscychresns.2009.04.013
Source: PubMed


The phenotypic association between fragile X syndrome (FXS) and autism is well established, but no studies have directly compared whole-brain anatomy between the two disorders. We performed voxel-based morphometry analyses of magnetic resonance imaging (MRI) scans on 10 individuals with FXS, 10 individuals with autism, and 10 healthy comparison subjects to identify volumetric changes in each disorder. Regional gray matter volumes within frontal, parietal, temporal, and cingulate gyri, as well as in the caudate nuclei and cerebellum, were larger in the FXS group relative to the autism group. In addition, volume increases in FXS were observed in frontal gyri and caudate nuclei compared to controls. The autism group exhibited volume increases in frontal and temporal gyri relative to the FXS group, and no volume increases relative to controls. Volumetric deficits relative to controls were observed in regions of the cerebellum for both groups, with additional deficits in parietal and temporal gyri for the FXS group. Our caudate nuclei and frontal gyri results may implicate dysfunction of frontostriatal circuitry in FXS. Cerebellar deficits suggest atypical development of the cerebellum contributing to the phenotype of both disorders, but further imply that unique cerebellar regions contribute to the phenotype of each disorder.

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    • "When different study samples contain different compositions of patients with different pathogenic mechanisms leading to clinical autism, there will be different cerebral fingerprints (Chen et al., 2011). Studies aiming to identify ASD subclusters according to variance in speech onset (Toal et al., 2010), age (Greimel et al., 2012; Nickl-Jockschat et al., 2012), sex (Beacher et al., 2012), macrocephaly (Bigler et al., 2010), and genetic syndromes (i.e., fragile X; Wilson et al., 2009) might help to dissect different biological underpinnings. The current study is the first one to focus on highfunctioning patients with ASD with above average IQ in an attempt to avoid the problem of etiological heterogeneity and to study a possibly homogenous sample regarding good overall brain function and the absence of severe mono-or oligogenetic syndromes. "
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    • "In the one study in which there was a Fragile X comparison group (Wilson et al., 2009), we only included the data from the ASD group without Fragile X. In the one study including both ASD and ADHD participants (Brieber et al., 2007), the individuals with ASD did not have symptoms of ADHD and vice versa. "
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    • "Kaufmann et al. (2003) were the first to directly compare children with FXS and ASD, finding hypoplasia of the posterosuperior vermis in both groups compared to controls. A study of 10 adults with FXS, 10 iASD, and 10 TD using VBM also reported decreased volume of the cerebellar vermis in FXS and iASD compared to TD; the FXS group had increased volumes of caudate and dorsolateral prefrontal cortex (PFC), and decreased volumes of left postcentral, middle temporal, and right fusiform gyrus (FG) compared to both ASD and TD (Wilson et al., 2009). Meguid et al. (2010) reported on a comparison of cortical thickness in 10 children with iAUT and 7 children with FXS + AUT; they found that that for the most part there were no significant differences in measures of cortical thickness, gyrification, or sulcal depth between the two groups, except that the iAUT had thinner cortex in the left medial frontal and anterior cingulate cortices, which correlated with an index of social maturity. "
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