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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    ABSTRACT: Autism spectrum disorder (ASD) is increasingly being recognized as an important issue in adult psychiatry and psychotherapy. High intelligence indicates overall good brain functioning and might thus present a particularly good opportunity to study possible cerebral correlates of core autistic features in terms of impaired social cognition, communication skills, the need for routines, and circumscribed interests. Anatomical MRI data sets for 30 highly intelligent patients with high-functioning autism and 30 pairwise-matched control subjects were acquired and analyzed with voxel-based morphometry. The grey matter volume of the pairwise-matched patients and the controls did not differ significantly. When correcting for total brain volume influences, the patients with ASD exhibited smaller left superior frontal volumes on a trend level. Heterogeneous volumetric findings in earlier studies might partly be explained by study samples biased by a high inclusion rate of secondary forms of ASD, which often go along with neuronal abnormalities. Including only patients with high IQ scores might have decreased the influence of secondary forms of ASD and might explain the absence of significant volumetric differences between the patients and the controls in this study.
    Psychiatry Research: Neuroimaging 08/2014; DOI:10.1016/j.pscychresns.2014.05.013 · 2.42 Impact Factor
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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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    ABSTRACT: Autism spectrum disorders (ASD) display significant heterogeneity. Although most neuroimaging studies in ASD have been designed to identify commonalities among affected individuals, rather than differences, some studies have explored variation within ASD. There have been two general types of approaches used for this in the neuroimaging literature to date: comparison of subgroups within ASD, and analyses using dimensional measures to link clinical variation to brain differences. This review focuses on structural and functional magnetic resonance imaging studies that have used these approaches to begin to explore heterogeneity between individuals with ASD. Although this type of data is yet sparse, recognition is growing of the limitations of behaviorally defined categorical diagnoses for understanding neurobiology. Study designs that are more informative regarding the sources of heterogeneity in ASD have the potential to improve our understanding of the neurobiological processes underlying ASD.
    Frontiers in Human Neuroscience 10/2013; 7:733. DOI:10.3389/fnhum.2013.00733 · 2.99 Impact Factor
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    • "Interestingly, multivariate analysis indicated that brain structure in children with idiopathic ASD was more similar to typically developing children and children with developmental delay than to children with fragile X syndrome , either with or without co-morbid autism (Hoeft et al., 2011). Other findings extend previous results to adults, indicating that increased volume within frontal, parietal, cingulate, caudate, and cerebellar regions differentiates between fragile X syndrome and ASD, while a pattern involving increased frontal and temporal volume is more characteristic of ASD (Wilson et al., 2009). The aforementioned neuroimaging studies examining fragile X syndrome and idiopathic ASD seem to indicate that brain-based phenotypes in these disorders differ more than they overlap. "
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    ABSTRACT: Autism Spectrum Disorder (ASD) refers to a group of heterogeneous neurodevelopmental disorders that are unified by impairments in reciprocal social communication and a pattern of inflexible behaviors. Recent genetic advances have resolved some of the complexity of the genetic architecture underlying ASD by identifying several genetic variants that contribute to the disorder. Different etiological pathways associated with ASD may converge through effects on common molecular mechanisms, such as synaptogenesis, neuronal motility, and axonal guidance. Recently, with more sophisticated techniques, neuroimaging, and neuropathological studies have provided some consistency of evidence that altered structure, activity, and connectivity within complex neural networks is present in ASD, compared to typically developing children. The imaging-genetics approach promises to help bridge the gap between genetic variation, resultant biological effects on the brain, and production of complex neuropsychiatric symptoms. Here, we review recent findings from the developing field of imaging-genetics applied to ASD. Studies to date have indicated that relevant risk genes are associated with alterations in circuits that mediate socio-emotional, visuo-spatial, and language processing. Longitudinal studies ideally focused on early development, in conjunction with investigation for gene-gene, and gene-environment interactions may move the promise of imaging-genetics in ASD closer to the clinical domain.
    Frontiers in Psychiatry 05/2012; 3:46. DOI:10.3389/fpsyt.2012.00046
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