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

Moreau, C.; Urchs, S.; Orban, P.; Schramm, C.; Dumas, G.; Labbe, A.; Huguet, G.; Douard, E.; Quirion, P.-O.; Lin, A.; Kushan, L.; Grot, S.; Luck, D.; Mendrek, A.; Potvin, S.; Stip, E.; Bourgeron, T.; Evans, A. C.; SimonsVIP Consortium,; Bearden, C. E.; Bellec, P.; Jacquemont, S.

doi:10.1101/862615

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bioRxiv · 10.1101/862615

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

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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. 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 dimensions contributing to complex idiopathic conditions. CNVs had large mirror effects on FC at the global and regional level. 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 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.

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Moreau, C., Urchs, S., Orban, P., Schramm, C., Dumas, G., Labbe, A., Huguet, G., Douard, E., Quirion, P.-O., Lin, A., Kushan, L., Grot, S., Luck, D., Mendrek, A., Potvin, S., Stip, E., Bourgeron, T., Evans, A. C., SimonsVIP Consortium,, Bearden, C. E., Bellec, P., Jacquemont, S.. 2019-12-06. Neuropsychiatric mutations delineate functional brain connectivity dimensions contributing to autism and schizophrenia. https://doi.org/10.1101/862615

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