Differential effect of disease-associated ST8SIA2 haplotype on cerebral white matter diffusion properties in schizophrenia and healthy controls.

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Serval ID
serval:BIB_5459030577F7
Type
Article: article from journal or magazin.
Collection
Publications
Title
Differential effect of disease-associated ST8SIA2 haplotype on cerebral white matter diffusion properties in schizophrenia and healthy controls.
Journal
Translational psychiatry
Author(s)
Fullerton J.M., Klauser P. (co-first), Lenroot R.K., Shaw A.D., Overs B., Heath A., Cairns M.J., Atkins J., Scott R., Schofield P.R., Weickert C.S., Pantelis C., Fornito A., Whitford T.J., Weickert T.W., Zalesky A.
Working group(s)
Australian Schizophrenia Research Bank
ISSN
2158-3188 (Electronic)
ISSN-L
2158-3188
Publication state
Published
Issued date
22/01/2018
Peer-reviewed
Oui
Volume
8
Number
1
Pages
21
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Brain white matter abnormalities are evident in individuals with schizophrenia, and also their first-degree relatives, suggesting that some alterations may relate to underlying genetic risk. The ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) gene, which encodes the alpha-2,8-sialyltransferase 8B enzyme that aids neuronal migration and synaptic plasticity, was previously implicated as a schizophrenia susceptibility gene. This study examined the extent to which specific haplotypes in ST8SIA2 influence white matter microstructure using diffusion-weighted imaging of individuals with schizophrenia (n = 281) and healthy controls (n = 172), recruited across five Australian sites. Interactions between diagnostic status and the number of haplotype copies (0 or ≥1) were tested across all white matter voxels with cluster-based statistics. Fractional anisotropy (FA) in the right parietal lobe was found to show a significant interaction between diagnosis and ST8SIA2 protective haplotype (p < 0.05, family-wise error rate (FWER) cluster-corrected). The protective haplotype was associated with increased FA in controls, but this effect was reversed in people with schizophrenia. White matter fiber tracking revealed that the region-of-interest was traversed by portions of the superior longitudinal fasciculus, corona radiata, and posterior limb of internal capsule. Post hoc analysis revealed that reduced FA in this regional juncture correlated with reduced IQ in people with schizophrenia. The ST8SIA2 risk haplotype copy number did not show any differential effects on white matter. This study provides a link between a common disease-associated haplotype and specific changes in white matter microstructure, which may relate to resilience or risk for mental illness, providing further compelling evidence for involvement of ST8SIA2 in the pathophysiology of schizophrenia.
Keywords
Adolescent, Adult, Anisotropy, Australia, Case-Control Studies, Diffusion Magnetic Resonance Imaging, Female, Haplotypes, Humans, Male, Middle Aged, Nerve Fibers, Myelinated/pathology, Schizophrenia/genetics, Schizophrenia/physiopathology, Sialyltransferases/genetics, White Matter/diagnostic imaging, White Matter/pathology, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
07/02/2019 10:09
Last modification date
03/12/2019 21:21
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