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

Nat Commun. 2020 Oct 19;11(1):5272. doi: 10.1038/s41467-020-18997-2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Attention Deficit Disorder with Hyperactivity / diagnostic imaging
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Autism Spectrum Disorder / diagnostic imaging
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / physiopathology
  • Autism Spectrum Disorder / psychology
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Child
  • Child, Preschool
  • Cognition
  • Cohort Studies
  • DNA Copy Number Variations
  • Female
  • Gene Deletion
  • Gene Duplication
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology
  • Young Adult