Neuropsychiatric mutations delineate functional brain connectivity dimensions contributing to autism and schizophrenia

Clara Moreau, et al.

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Dec 09, 2019

Received Date: 16th November 19

Clara Moreau, Sebastian Urchs, Pierre Orban, Catherine Schramm, Guillaume Dumas, Aurélie Labbe, Guillaume Huguet, Elise Douard, Pierre-Olivier Quirion, Amy Lin, Leila Kushan, Stephanie Grot, David Luck, Adrianna Mendrek, Stephane Potvin, Emmanuel Stip, >span class="nlm-surname">Bourgeron, Alan C. Evans, Carrie E. Bearden, Pierre Bellec, Sebastien Jacquemont, Simons Variation in Individuals Project Consortium

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) networks remains unclear.
We analyzed resting-state functional magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We used CNV FC-signatures to identify major dimensions contributing to complex idiopathic conditions.
CNVs had large mirror effects on FC at the global and regional level, and their effect-sizes were twice as large as those of idiopathic conditions. Thalamus, somatomotor, and posterior insula regions played a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibited worse behavioral and cognitive symptoms. These seemingly distinct neuropsychiatric mutations showed similar gene co-expression patterns and converged on FC dimensions, that may represent mechanistic building blocks shared across idiopathic conditions.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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