Atypical cortical networks in children at high-genetic risk of psychiatric and eurodevelopmental disorders

Doherty, Joanne L., Cunningham, Adam C., Chawner, Samuel J. R. A., Moss, Hayley M., Dima, Diana C. ORCID: https://orcid.org/0000-0002-9612-5574, Linden, David E. J. ORCID: https://orcid.org/0000-0002-5638-9292, Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862, van den Bree, Marianne B. M. ORCID: https://orcid.org/0000-0002-4426-3254 and Singh, Krish D. ORCID: https://orcid.org/0000-0002-3094-2475 2024. Atypical cortical networks in children at high-genetic risk of psychiatric and eurodevelopmental disorders. Neuropsychopharmacology 49 , pp. 368-376. 10.1038/s41386-023-01628-x

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Abstract

Although many genetic risk factors for psychiatric and neurodevelopmental disorders have been identified, the neurobiological route from genetic risk to neuropsychiatric outcome remains unclear. 22q11.2 deletion syndrome (22q11.2DS) is a copy number variant (CNV) syndrome associated with high rates of neurodevelopmental and psychiatric disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia. Alterations in neural integration and cortical connectivity have been linked to the spectrum of neuropsychiatric disorders seen in 22q11.2DS and may be a mechanism by which the CNV acts to increase risk. In this study, magnetoencephalography (MEG) was used to investigate electrophysiological markers of local and global network function in 34 children with 22q11.2DS and 25 controls aged 10–17 years old. Resting-state oscillatory activity and functional connectivity across six frequency bands were compared between groups. Regression analyses were used to explore the relationships between these measures, neurodevelopmental symptoms and IQ. Children with 22q11.2DS had altered network activity and connectivity in high and low frequency bands, reflecting modified local and long-range cortical circuitry. Alpha and theta band connectivity were negatively associated with ASD symptoms while frontal high frequency (gamma band) activity was positively associated with ASD symptoms. Alpha band activity was positively associated with cognitive ability. These findings suggest that haploinsufficiency at the 22q11.2 locus impacts short and long-range cortical circuits, which could be a mechanism underlying neurodevelopmental and psychiatric vulnerability in this high-risk group.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Psychology
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	0893-133X
Funders:	Medical Research Council, Wellcome Trust, Baily Thomas Charitable Fund
Date of First Compliant Deposit:	10 July 2023
Date of Acceptance:	1 June 2023
Last Modified:	11 Jun 2024 09:47
URI:	https://orca.cardiff.ac.uk/id/eprint/160920

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