Abnormal nodal and global network organization in resting state functional MRI from subjects with the 22q11 deletion syndrome

Teuntje A D Pelgrim,Claudia Ornstein,Angeles Tepper,Rosemarie Fritsch,Nicolas Crossley,Analía Cuiza,Gabriela Repetto,Carlos Mena,Juan Pablo Ramirez-Mahaluf,Luz María Alliende,Barbara Iruretagoyena,Cristian Tejos,Matthijs G Bossong,Juan Pablo Cruz

doi:10.1038/s41598-021-00873-8

Abstract

The 22q11 deletion syndrome is a genetic disorder associated with a high risk of developing psychosis, and is therefore considered a neurodevelopmental model for studying the pathogenesis of schizophrenia. Studies have shown that localized abnormal functional brain connectivity is present in 22q11 deletion syndrome like in schizophrenia. However, it is less clear whether these abnormal cortical interactions lead to global or regional network disorganization as seen in schizophrenia. We analyzed from a graph-theory perspective fMRI data from 40 22q11 deletion syndrome patients and 67 healthy controls, and reconstructed functional networks from 105 brain regions. Between-group differences were examined by evaluating edge-wise strength and graph theoretical metrics of local (weighted degree, nodal efficiency, nodal local efficiency) and global topological properties (modularity, local and global efficiency). Connectivity strength was globally reduced in patients, driven by a large network comprising 147 reduced connections. The 22q11 deletion syndrome network presented with abnormal local topological properties, with decreased local efficiency and reductions in weighted degree particularly in hub nodes. We found evidence for abnormal integration but intact segregation of the 22q11 deletion syndrome network. Results suggest that 22q11 deletion syndrome patients present with similar aberrant local network organization as seen in schizophrenia, and this network configuration might represent a vulnerability factor to psychosis.

Highlights

The 22q11 deletion syndrome is a genetic disorder associated with a high risk of developing psychosis, and is considered a neurodevelopmental model for studying the pathogenesis of schizophrenia
We further found a significant reduction of local efficiency in six nodes in 22q11 deletion syndrome patients compared to controls, and two nodes that were significantly increased in the patient group (Fig. 2D)
The present study was designed to investigate whole-brain functional connectivity in the 22q11 deletion syndrome, looking at local and global topological properties of the functional network using a graph theoretical approach

Summary

Introduction

The 22q11 deletion syndrome is a genetic disorder associated with a high risk of developing psychosis, and is considered a neurodevelopmental model for studying the pathogenesis of schizophrenia. Studies have shown that localized abnormal functional brain connectivity is present in 22q11 deletion syndrome like in schizophrenia. It is less clear whether these abnormal cortical interactions lead to global or regional network disorganization as seen in schizophrenia. A previous study using a graph-theory approach focused on the modular organization of the functional network in 22q11 deletion syndrome patients, finding an increased segregation in the network compared to healthy controls, both in children and young a dults[25]. We hypothesized that 22q11 deletion syndrome patients would present some abnormalities that are similar to those of patients with schizophrenia These would involve localized changes in frontal regions and hub regions, as well as a decreased local efficiency, which could be related to their vulnerability to psychosis

Objectives

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Results

Conclusion