Dataset Information

Mutations associated with neuropsychiatric conditions 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. 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.

SUBMITTER: Moreau CA

PROVIDER: S-EPMC7573583 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia.

Moreau Clara A CA Urchs Sebastian G W SGW Kuldeep Kumar K Orban Pierre P Schramm Catherine C Dumas Guillaume G Labbe Aurélie A Huguet Guillaume G Douard Elise E Quirion Pierre-Olivier PO Lin Amy A Kushan Leila L Grot Stephanie S Luck David D Mendrek Adrianna A Potvin Stephane S Stip Emmanuel E Bourgeron Thomas T Evans Alan C AC Bearden Carrie E CE Bellec Pierre P Jacquemont Sebastien S

Nature communications 20201019 1

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 ...[more]

PMID: 33077750

Similar Datasets

Project description:The genetic basis and human-specific character of schizophrenia has led to the hypothesis that human brain evolution may have played a role in the development of the disorder. We examined schizophrenia-related changes in brain connectivity in the context of evolutionary changes in human brain wiring by comparing in vivo neuroimaging data from humans and chimpanzees, one of our closest living evolutionary relatives and a species with which we share a very recent common ancestor. We contrasted the connectome layout between the chimpanzee and human brain and compared differences with the pattern of schizophrenia-related changes in brain connectivity as observed in patients. We show evidence of evolutionary modifications of human brain connectivity to significantly overlap with the cortical pattern of schizophrenia-related dysconnectivity (P < 0.001, permutation testing). We validated these effects in three additional, independent schizophrenia datasets. We further assessed the specificity of effects by examining brain dysconnectivity patterns in seven other psychiatric and neurological brain disorders (including, among others, major depressive disorder and obsessive-compulsive disorder, arguably characterized by behavioural symptoms that are less specific to humans), which showed no such associations with modifications of human brain connectivity. Comparisons of brain connectivity across humans, chimpanzee and macaques further suggest that features of connectivity that evolved in the human lineage showed the strongest association to the disorder, that is, brain circuits potentially related to human evolutionary specializations. Taken together, our findings suggest that human-specific features of connectome organization may be enriched for changes in brain connectivity related to schizophrenia. Modifications in human brain connectivity in service of higher order brain functions may have potentially also rendered the brain vulnerable to brain dysfunction.

Project description:Schizophrenia and autism spectrum disorder (ASD) are two prevalent neurodevelopmental disorders sharing some similar genetic basis and clinical features. The extent to which they share common neural substrates remains unclear. Resting-state fMRI data were collected from 35 drug-naïve adolescent participants with first-episode schizophrenia (15.6?±?1.8 years old) and 31 healthy controls (15.4?±?1.6 years old). Data from 22 participants with ASD (13.1?±?3.1 years old) and 21 healthy controls (12.9?±?2.9 years old) were downloaded from the Autism Brain Imaging Data Exchange. Resting-state functional networks were constructed using predefined regions of interest. Multivariate pattern analysis combined with multi-task regression feature selection methods were conducted in two datasets separately. Classification between individuals with disorders and controls was achieved with high accuracy (schizophrenia dataset: accuracy?=?83%; ASD dataset: accuracy?=?80%). Shared atypical brain connections contributing to classification were mostly present in the default mode network (DMN) and salience network (SN). These functional connections were further related to severity of social deficits in ASD (p?=?0.002). Distinct atypical connections were also more related to the DMN and SN, but showed different atypical connectivity patterns between the two disorders. These results suggest some common neural mechanisms contributing to schizophrenia and ASD, and may aid in understanding the pathology of these two neurodevelopmental disorders. Autism Res 2017, 10: 1776-1786. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:Autism spectrum disorder (ASD) and schizophrenia are two common neurodevelopmental disorders which share several genetic and behavioral features. The present study identified common neural mechanisms contributing to ASD and schizophrenia using resting-state functional MRI data. The results may help to understand the pathology of these two neurodevelopmental disorders.

Dataset Information

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia.

Publications

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets