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Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence.

ABSTRACT: During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact with the development of white matter microstructure. This interaction may be present beyond the phenotype of autism in siblings of individuals with ASC, who are 10 to 20 times more likely to develop certain forms of ASC. We use diffusion tensor imaging to examine how white matter microstructure measurements correlate with age in typically developing individuals, and how this correlation differs in n=43 adolescents with ASC and their n=38 siblings. Correlations observed in n=40 typically developing individuals match developmental changes noted in previous longitudinal studies. In comparison, individuals with ASC display weaker negative correlation between age and mean diffusivity in a broad area centred in the right superior longitudinal fasciculus. These differences may be caused either by increased heterogeneity in ASC or by temporal alterations in the group's developmental pattern. Siblings of individuals with ASC also show diminished negative correlation between age and one component of mean diffusivity-second diffusion eigenvalue-in the right superior longitudinal fasciculus. As the observed differences match for location and correlation directionality in our comparison of typically developing individuals to those with ASC and their siblings, we propose that these alterations constitute a part of the endophenotype of autism.

SUBMITTER: Lisiecka DM

PROVIDER: S-EPMC4354353 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence.

Lisiecka D M DM Holt R R Tait R R Ford M M Lai M-C MC Chura L R LR Baron-Cohen S S Spencer M D MD Suckling J J

Translational psychiatry 20150317

During adolescence, white matter microstructure undergoes an important stage of development. It is hypothesized that the alterations of brain connectivity that have a key role in autism spectrum conditions (ASCs) may interact with the development of white matter microstructure. This interaction may be present beyond the phenotype of autism in siblings of individuals with ASC, who are 10 to 20 times more likely to develop certain forms of ASC. We use diffusion tensor imaging to examine how white ...[more]

PMID: 25781228

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Project description:Neighborhood disadvantage and community violence are common in poor, urban communities and are risk factors for emotional dysfunction. Emotional processes are supported by neural circuitry that includes the prefrontal cortex (PFC), hippocampus, amygdala, and hypothalamus. These brain regions are connected by white matter pathways that include the cingulum bundle, uncinate fasciculus, stria terminalis, and fornix. Emotional function varies with the microstructure of these white matter pathways. However, it is not clear whether the microstructure of these pathways varies with risk factors for emotional dysfunction (e.g., neighborhood disadvantage and violence exposure). Therefore, determining the relationships between neighborhood disadvantage, violence exposure, and white matter microstructure may offer insight into the neural mechanisms by which adverse life experiences alter developing neural systems. The current study investigated the association that exposure to neighborhood disadvantage and violence have with the quantitative anisotropy (QA), a measure of the amount of directional water diffusion, of the cingulum bundle, uncinate fasciculus, stria terminalis, and fornix. Neighborhood disadvantage (Mage = 11.20) and violence exposure (MW1age = 11.20; MW2age = 13.05; MW3age = 16.20; MW4age = 19.25) were assessed during adolescence and participants returned for magnetic resonance imaging as young adults (N = 303; Mage = 20.25, SD = 1.55), during which diffusion weighted brain images were collected. The QA of the cingulum bundle, uncinate fasciculus, and stria terminalis/fornix varied negatively with neighborhood disadvantage such that the QA of these white matter tracts decreased as neighborhood disadvantage increased. Violence exposure was not related to QA in any tract (i.e., cingulum bundle, uncinate fasciculus, and stria terminalis/fornix) after correction for multiple comparisons. These results suggest that an adolescent's neighborhood may play an important role in the microstructure (i.e., QA) of white matter pathways that connect brain regions that support emotional function.

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Dataset Information

Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence.

Publications

Developmental white matter microstructure in autism phenotype and corresponding endophenotype during adolescence.

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