Mutations Associated with Neuropsychiatric Conditions Delineate Functional Brain Connectivity Dimensions Contributing to Autism and Schizophrenia

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Oct 20

PMID 33077750

Citations 28

Authors

Clara A Moreau

Sebastian G W Urchs

Kumar Kuldeep

Pierre Orban

Catherine Schramm

Guillaume Dumas

Aurelie Labbe

Guillaume Huguet

Elise Douard

Pierre-Olivier Quirion

Amy Lin

Leila Kushan

Stephanie Grot

David Luck

Adrianna Mendrek

Stephane Potvin

Emmanuel Stip

Thomas Bourgeron

Alan C Evans

Carrie E Bearden

Pierre Bellec

Sebastien Jacquemont

Affiliations

Soon will be listed here.

Abstract

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.

Citing Articles

Synaptic-dependent developmental dysconnectivity in 22q11.2 deletion syndrome.

Alvino F, Gini S, Minetti A, Pagani M, Sastre-Yague D, Barsotti N Sci Adv. 2025; 11(11):eadq2807.

PMID: 40073125 PMC: 11900866. DOI: 10.1126/sciadv.adq2807.

Differential links in 16p11.2 deletion carriers reveal aberrant connections between large-scale networks.

Qureshi A, Nielsen J, Sepulcre J Cereb Cortex. 2025; 35(2).

PMID: 40007052 PMC: 11859958. DOI: 10.1093/cercor/bhae474.

Delineating a Pathway for the Discovery of Functional Connectome Biomarkers of Autism.

Park S, Thomson P, Kiar G, Castellanos F, Milham M, Bernhardt B Adv Neurobiol. 2024; 40:511-544.

PMID: 39562456 DOI: 10.1007/978-3-031-69491-2_18.

Language Profiles of School-Age Children With 16p11.2 Copy Number Variants in a Clinically Ascertained Cohort.

Verbesselt J, Breckpot J, Zink I, Swillen A J Speech Lang Hear Res. 2024; 67(11):4487-4503.

PMID: 39418585 PMC: 11567083. DOI: 10.1044/2024_JSLHR-24-00257.

The pleiotropic spectrum of proximal 16p11.2 CNVs.

Auwerx C, Kutalik Z, Reymond A Am J Hum Genet. 2024; 111(11):2309-2346.

PMID: 39332410 PMC: 11568765. DOI: 10.1016/j.ajhg.2024.08.015.

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