Genetic risk for schizophrenia and developmental delay is associated with shape and microstructure of midline white-matter structures

被引：16

作者：

Drakesmith, Mark ^{[1
,2
]}

Parker, Greg D. ^{[1
,2
,3
]}

Smith, Jacqueline ^{[2
,4
]}

Linden, Stefanie C. ^{[2
,4
]}

Rees, Elliott ^{[2
,4
]}

Williams, Nigel ^{[2
,4
]}

Owen, Michael J. ^{[2
,4
]}

van den Bree, Marianne ^{[2
,4
]}

Hall, Jeremy ^{[2
,4
]}

Jones, Derek K. ^{[1
,2
,5
]}

Linden, David E. J. ^{[1
,2
,4
,6
]}

机构：

[1] Cardiff Univ, Sch Psychol, CUBRIC, Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales

[2] Cardiff Univ, NMHRI, Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales

[3] Cardiff Univ, Sch Biosci, Expt MRI Ctr EMRIC, Sir Martin Evans Bldg,Museum Ave, Cardiff CF10 3AX, S Glam, Wales

[4] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales

[5] Australian Catholic Univ, Fac Hlth Sci, Sch Psychol, Melbourne, Vic 3065, Australia

[6] Maastricht Univ, Fac Hlth Med & Life Sci, Sch Mental Hlth & Neurosci, Maastricht, Netherlands

来源：

TRANSLATIONAL PSYCHIATRY | 2019年 / 9卷 / 1期

基金：

英国惠康基金;

关键词：

22Q11.2 DELETION SYNDROME; SURFACE-BASED ANALYSIS; DIFFUSION TENSOR MRI; VELOCARDIOFACIAL SYNDROME; CORPUS-CALLOSUM; CINGULUM BUNDLE; BRAIN; ABNORMALITIES; CHILDREN; SEGMENTATION;

D O I：

10.1038/s41398-019-0440-7

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Genomic copy number variants (CNVs) are amongst the most highly penetrant genetic risk factors for neuropsychiatric disorders. The scarcity of carriers of individual CNVs and their phenotypical heterogeneity limits investigations of the associated neural mechanisms and endophenotypes. We applied a novel design based on CNV penetrance for schizophrenia (Sz) and developmental delay (DD) that allows us to identify structural sequelae that are most relevant to neuropsychiatric disorders. Our focus on brain structural abnormalities was based on the hypothesis that convergent mechanisms contributing to neurodevelopmental disorders would likely manifest in the macro- and microstructure of white matter and cortical and subcortical grey matter. Twenty one adult participants carrying neuropsychiatric risk CNVs (including those located at 22q11.2, 15q11.2, 1q21.1, 16p11.2 and 17q12) and 15 age- and gender-matched controls underwent T1-weighted structural, diffusion and relaxometry MRI. The macro- and microstructural properties of the cingulum bundles were associated with penetrance for both developmental delay and schizophrenia, in particular curvature along the anterior- posterior axis (Sz: p(corr) = 0.026; DD: p(corr) = 0.035) and intracellular volume fraction (Sz: p(corr) = 0.019; DD: p(corr) = 0.064). Further principal component analysis showed alterations in the interrelationships between the volumes of several midline white-matter structures (Sz: p(corr) = 0.055; DD: p(corr) = 0.027). In particular, the ratio of volumes in the splenium and body of the corpus callosum was significantly associated with both penetrance scores (Sz: p = 0.037; DD; p = 0.006). Our results are consistent with the notion that a significant alteration in developmental trajectories of midline white-matter structures constitutes a common neurodevelopmental aberration contributing to risk for schizophrenia and intellectual disability.

引用

页数：13