M84. The Relationship Between White Matter Connections and Cognitive Domains in Children at Genetic Risk for Schizophrenia

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Background: Schizophrenia (SZ) has been recognized as a neurodevelopmental disorder with language and working memory deficits. Previous neuroimaging studies of SZ patients report decreased fractional anisotropy in anatomical white matter tracts serving these cognitive functions. However, the timeline of WM abnormalities and their relationship to the development of cognitive deficits is poorly understood. This study aims to utilize diffusion imaging and neurocognitive assessments to investigate the relationship between potential structural alterations in WM tracts associated with language and working memory scores in children at genetic high risk (GHR) for the disease compared to matched controls. Methods: 3T diffusion-weighted images of children aged 7 to 12 (18 controls [HC] and 14 at GHR for SZ) were collected at the Massachusetts Institute of Technology. After quality control steps, whole brain 2-tensor tractography was performed. Two bilateral WM tracts of interest were specifically extracted: a language tract, the arcuate fasciculus (AF), and a working memory tract, the superior longitudinal II fasciculus (SLF-ii). The fractional anisotropy of the tissue (FA-t), a novel more biologically specific measure of white matter tissue microstructure, was obtained in each tract and compared between the GHR and HC children. Group comparisons of FA-t between GHR and HC children were conducted utilizing Mann-Whitney U tests for each WM tract of interest. Spearman correlations between performance on the Similarities (language) and Letter-Number Sequencing (working memory) subtests of the Weschler’s Intelligence Scale for Children (Fourth Edition) were completed with the FA-t values in the AF and SLF-ii, respectively. Results: Preliminary analyses demonstrate that there is a significant 16.6% decrease in FA-t in the right AF in GHR children under the age of 9 (P < .01). These differences were not present in the right AF in GHR children between the ages of 10 and 12. There were no significant differences found in the SLF-ii in GHR children. FA-t values in the right AF were significantly correlated with the Similarities subtest (rho = 0.57, P = .03) for all GHR children but not in HC children. There were no significant correlations between the SLF-ii and the Letter-Number Sequencing task in GHR or HC children. Conclusion: From late childhood into puberty, the extent of white matter myelination exhibits dramatic maturational changes. Our findings of a reduction in FA-t in the right AF in children under 9 suggest that early maturational alterations could be present in GHR children and that these early structural differences may impact specific cognitive domains. The significant correlation between right AF FA-t and performance on the Similarities subtest in GHR, but not control children, reveals that early structural differences may mediate the persistent language differences previously reported in patients with schizophrenia.

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