Brain morphometry in 22q11.2 deletion syndrome: an exploration of differences in cortical thickness, surface area, and their contribution to cortical volume

M Gudbrandsen,C Mann,A Bletsch,C E Bearden,E Daly,D G M Murphy,M Rogdaki,C M Murphy,M C Craig,Christine Ecker,L Kushan,C E Blackmore

doi:10.1038/s41598-020-75811-1

M Gudbrandsen, C Mann + Show 10 more

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https://doi.org/10.1038/s41598-020-75811-1

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Abstract

22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans, with a heterogenous clinical presentation including medical, behavioural and psychiatric conditions. Previous neuroimaging studies examining the neuroanatomical underpinnings of 22q11.2DS show alterations in cortical volume (CV), cortical thickness (CT) and surface area (SA). The aim of this study was to identify (1) the spatially distributed networks of differences in CT and SA in 22q11.2DS compared to controls, (2) their unique and spatial overlap, as well as (3) their relative contribution to observed differences in CV. Structural MRI scans were obtained from 62 individuals with 22q11.2DS and 57 age-and-gender-matched controls (aged 6–31). Using FreeSurfer, we examined differences in vertex-wise estimates of CV, CT and SA at each vertex, and compared the frequencies of vertices with a unique or overlapping difference for each morphometric feature. Our findings indicate that CT and SA make both common and unique contributions to volumetric differences in 22q11.2DS, and in some areas, their strong opposite effects mask differences in CV. By identifying the neuroanatomic variability in 22q11.2DS, and the separate contributions of CT and SA, we can start exploring the shared and distinct mechanisms that mediate neuropsychiatric symptoms across disorders, e.g. 22q11.2DS-related ASD and/or psychosis/schizophrenia.

Highlights

22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans, with a heterogenous clinical presentation including medical, behavioural and psychiatric conditions
Given recent evidence[7,11], it was expected that the spatial distribution of differences in cortical thickness (CT) and surface area (SA) significantly varies across the cortex between individuals with the 22q11.2 microdeletion and typically developing (TD) controls, and that the vertex-wise overlap of between-group differences in CT and SA exerts a significant effect on measures of cortical volume (CV) in some areas of the cortex
This is the first study to quantify the overlap of vertex-wise differences in cortical thickness (CT) and surface area (SA) in individuals with 22q11.2DS compared to controls, as well as to identify their influence on between-group differences in cortical volume (CV)

Summary

Introduction

22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans, with a heterogenous clinical presentation including medical, behavioural and psychiatric conditions. A vertex-wise approach will be used to examine vertices across the entire cortical surface in order to identify clusters with significant between-group differences spanning across several brain regions This is useful when examining complex and heterogeneous neurodevelopmental disorders, such as 22q11.2DS, where structural alterations have been reported to be spatially distributed, affecting several large-scale neurocognitive networks[10]. The aim of the present study was to investigate regional differences in CV, SA, and CT—as well as their relationship—in individuals with 22q11.2DS compared to typically developing controls—using a vertex-based approach This approach allowed us to identify: (1) the spatially distributed networks of differences in CT and SA; (2) the degree of spatial overlap between them; and (3) their relative contribution to observed differences in regional CV. Given recent evidence[7,11], it was expected that the spatial distribution of differences in CT and SA significantly varies across the cortex between individuals with the 22q11.2 microdeletion and TD controls, and that the vertex-wise overlap of between-group differences in CT and SA exerts a significant effect on measures of CV in some areas of the cortex (e.g. the frontal lobes)

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