Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk

Diana C. Dima*, Rachael Adams, Stefanie C. Linden, Alister Baird, Jacqueline Smith, Sonya Foley, Gavin Perry, Bethany C. Routley, Lorenzo Magazzini, Mark Drakesmith, Nigel Williams, Joanne Doherty, Marianne B. M. van den Bree, Michael J. Owen, Jeremy Hall, David E. J. Linden, Krish D. Singh

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Rare copy number variants associated with increased risk for neurodevelopmental and psychiatric disorders (referred to as ND-CNVs) are characterized by heterogeneous phenotypes thought to share a considerable degree of overlap. Altered neural integration has often been linked to psychopathology and is a candidate marker for potential convergent mechanisms through which ND-CNVs modify risk; however, the rarity of ND-CNVs means that few studies have assessed their neural correlates. Here, we used magnetoencephalography (MEG) to investigate resting-state oscillatory connectivity in a cohort of 42 adults with ND-CNVs, including deletions or duplications at 22q11.2, 15q11.2, 15q13.3, 16p11.2, 17q12, 1q21.1, 3q29, and 2p16.3, and 42 controls. We observed decreased connectivity between occipital, temporal, and parietal areas in participants with ND-CNVs. This pattern was common across genotypes and not exclusively characteristic of 22q11.2 deletions, which were present in a third of our cohort. Furthermore, a data-driven graph theory framework enabled us to successfully distinguish participants with ND-CNVs from unaffected controls using differences in node centrality and network segregation. Together, our results point to alterations in electrophysiological connectivity as a putative common mechanism through which genetic factors confer increased risk for neurodevelopmental and psychiatric disorders.

Original languageEnglish
Article number324
Number of pages11
JournalTranslational Psychiatry
Volume10
Issue number1
DOIs
Publication statusPublished - 21 Sept 2020

Keywords

  • 22Q11.2 DELETION SYNDROME
  • RESTING-STATE NETWORKS
  • INHIBITION BALANCE
  • PRODROMAL SYMPTOMS
  • 16P11.2 DELETION
  • CONNECTIVITY
  • SCHIZOPHRENIA
  • EXCITATION
  • BRAIN
  • ADOLESCENTS

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