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

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 behavioural 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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

* Extensive efforts have, in particular, been directed towards 1) Demonstrating the robustness of the results by using novel data, performing an array of sensitivity analyses, and systematic comparison with previously published results in autism and schizophrenia 2) Fully reshaping the last section of the manuscript on gene expression. This included analyzing expression data genome-wide and performing a new array of methods that generated results of significant interest.

* https://github.com/surchs/Neuropsychiatric_CNV_code_supplement