Dataset Information

Altered white-matter integrity in unaffected siblings of probands with autism spectrum disorders.

ABSTRACT: Despite the evidence of altered white-matter tract property in individuals with autism spectrum disorder (ASD), little is known about their unaffected siblings. This study aimed to investigate white-matter integrity in unaffected siblings of ASD probands. Thirty-nine unaffected siblings (mean age 15.6?±?6.0 years; 27 males, 69.2%) and 39 typically developing controls (TDC) (14.2?±?5.6 years; 26 males, 66.7%) were assessed with diffusion spectrum images and neuropsychological tests. Using the tract-based automatic analysis and the threshold-free cluster weighted (TFCW) scores, we searched for the segments among 76 tracts with the largest difference over the entire brain compared to TDC. Tract integrity was quantified by calculating the mean generalized fractional anisotropy (mGFA) values of the segments with the largest difference in TFCW scores. Unaffected siblings showed reduced mGFA in the bilateral frontal aslant tracts, the right superior longitudinal fasciculus 2 (SLF2), the frontostriatal tracts from the right dorsolateral and left ventrolateral prefrontal cortices, the thalamic radiations of the left ventral and the right dorsal thalamus, the callosal fibers of the splenium, and the increased mGFA of the callosal fibers of the precuneus and the left inferior longitudinal fasciculus. Among these, reduced right SLF2 mGFA was associated with social awareness deficits; impaired frontostriatal tract was associated with internalizing problems, while right frontal aslant tract integrity was associated with visual memory deficits. In conclusion, unaffected siblings showed the aberrant integrity of several white-matter tracts, which were correlated with clinical symptoms and neurocognitive dysfunction. The altered tract integrity could be further examined in the probands with ASD. Hum Brain Mapp 38:6053-6067, 2017. © 2017 Wiley Periodicals, Inc.

SUBMITTER: Chien YL

PROVIDER: S-EPMC6866809 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Altered white-matter integrity in unaffected siblings of probands with autism spectrum disorders.

Chien Yi-Ling YL Chen Yu-Jen YJ Hsu Yung-Chin YC Tseng Wen-Yih Isaac WI Gau Susan Shur-Fen SS

Human brain mapping 20170920 12

Despite the evidence of altered white-matter tract property in individuals with autism spectrum disorder (ASD), little is known about their unaffected siblings. This study aimed to investigate white-matter integrity in unaffected siblings of ASD probands. Thirty-nine unaffected siblings (mean age 15.6 ± 6.0 years; 27 males, 69.2%) and 39 typically developing controls (TDC) (14.2 ± 5.6 years; 26 males, 66.7%) were assessed with diffusion spectrum images and neuropsychological tests. Using the tra ...[more]

PMID: 28940697

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Project description:Autism spectrum disorder (ASD) is currently viewed as a disorder of cortical systems connectivity, with a heavy emphasis being on the structural integrity of white matter tracts. However, the majority of the literature to date has focused on children with ASD. Understanding the integrity of white matter tracts in adults may help reveal the nature of ASD pathology in adulthood and the potential contributors to cognitive impairment. This study examined white matter water diffusion using diffusion tensor imaging in relation to neuropsychological measures of cognition in a sample of 45 adults with ASD compared to 20 age, gender, and full-scale-IQ-matched healthy volunteers. Tract-based spatial statistics were used to assess differences in diffusion along white matter tracts between groups using permutation testing. The following neuropsychological measures of cognition were assessed: processing speed, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Results indicated that fractional anisotropy (FA) was significantly reduced in adults with ASD in the anterior thalamic radiation (P = 0.022) and the right cingulum (P = 0.008). All neuropsychological measures were worse in the ASD group, but none of the measures significantly correlated with reduced FA in either tract in the adults with ASD or in the healthy volunteers. Together, this indicates that the tracts that are the most impacted in autism may not be (at least directly) responsible for the behavioral deficits in ASD. Autism Res 2020, 13: 702-714. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: White matter tracts are the data cables in the brain that efficiently transfer information, and damage to these tracts could be the cause for the abnormal behaviors that are associated with autism. We found that two long-range tracts (the anterior thalamic radiation and the cingulum) were both impaired in autism but were not directly related to the impairments in behavior. This suggests that the abnormal tracts and behavior are the effects of another underlying mechanism.

Project description:BACKGROUND:Altered structural network-connectivity has been reported in psychotic disorder but whether these alterations are associated with genetic vulnerability, and/or with phenotypic variation, has been less well examined. This study examined i) whether differences in network-connectivity exist between patients with psychotic disorder, siblings of patients with psychotic disorder and controls, and ii) whether network-connectivity alterations vary with (subclinical) symptomatology. METHODS:Network-connectivity measures (global efficiency (GE), density, local efficiency (LE), clustering coefficient (CC)) were derived from diffusion weighted imaging (DWI) and were compared between 85 patients with psychotic disorder, 93 siblings without psychotic disorder and 80 healthy comparison subjects using multilevel regression models. In patients, associations between Positive and Negative Syndrome Scale (PANSS) symptoms and topological measures were examined. In addition, interactions between subclinical psychopathology and sibling/healthy comparison subject status were examined in models of topological measures. RESULTS:While there was no main effect of group with respect to GE, density, LE and CC, siblings had a significantly higher CC compared to patients (B = 0.0039, p = .002). In patients, none of the PANSS symptom domains were significantly associated with any of the four network-connectivity measures. The two-way interaction between group and SIR-r positive score in the model of LE was significant (χ2 = 6.24, p = .01, df = 1). In the model of CC, the interactions between group and respectively SIS-r positive (χ2 = 5.59, p = .02, df = 1) and negative symptom scores (χ2 = 4.71, p = .03, df = 1) were significant. Stratified analysis showed that, in siblings, decreased LE and CC was significantly associated with increased SIS-r positive scores (LE: B = -0.0049, p = .003, CC: B = -0.0066, p = .01) and that decreased CC was significantly associated with increased SIS-r negative scores (B = -0.012, p = .003). There were no significant interactions between group and SIS-r scores in the models of GE and density. CONCLUSION:The findings indicate absence of structural network-connectivity alterations in individuals with psychotic disorder and in individuals at higher than average genetic risk for psychotic disorder, in comparison with healthy subjects. The differential subclinical symptom-network connectivity associations in siblings with respect to controls may be a sign of psychosis vulnerability in the siblings.

Project description:BackgroundRecent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD.Materials and methodsWe used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n = 20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at 3 years of age for diagnostic outcome. Three outcome groups were defined (ASD, n = 9; typical development, n = 8; non-typical development, n = 3).ResultsASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e., prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.LimitationsOur study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples.ConclusionThese preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.

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Altered white-matter integrity in unaffected siblings of probands with autism spectrum disorders.

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Altered white-matter integrity in unaffected siblings of probands with autism spectrum disorders.

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