title: Structural and functional connectivity in the default mode network in 22q11.2 deletion syndrome.
abstract: BACKGROUND
  The neural endophenotype associated with 22q11.2 deletion syndrome (22q11DS) includes deviant cortical development and alterations in brain connectivity. Resting-state functional magnetic resonance imaging (fMRI) findings also reported disconnectivity within the default mode network (DMN). In this study, we explored the relationship between functional and structural DMN connectivity and their changes with age in patients with 22q11DS in comparison to control participants. Given previous evidence of an association between DMN disconnectivity and the manifestation of psychotic symptoms, we further investigated this relationship in our group of patients with 22q11DS.
  
  
  METHODS
  T1-weighted, diffusion, and resting-state fMRI scans were acquired from 41 patients with 22q11DS and 43 control participants aged 6 to 28 years. A data-driven approach based on independent component analysis (ICA) was used to identify the DMN and to define regions of interest for the structural and functional connectivity analysis. Prodromal psychotic symptoms were assessed in adolescents and adults using the positive symptom scores of the Structured Interview of Prodromal Syndromes (SIPS). Connectivity measures were compared between groups and correlated with age. Repeating the between-group analysis in three different age bins further assessed the presence of age-related alterations in DMN connectivity. Structural and functional connectivity measures were then correlated with the SIPS scores.
  
  
  RESULTS
  A simultaneous reduction of functional and structural connectivity between core medial nodes of the DMN was observed. Furthermore, structural connectivity measures significantly increased with age in the control group but not in patients with 22q11DS, suggesting the presence of an age-related alteration of the DMN structural connections. No correlations were found between the DMN disconnectivity and expression of prodromal symptoms in 22q11DS.
  
  
  CONCLUSIONS
  These findings indicate the presence of functional and structural DMN disconnectivity in 22q11DS and that patients with 22q11DS fail to develop normal structural connections between medial DMN nodes. This suggests the presence of altered neurodevelopmental trajectories in 22q11DS.
authors.affiliation: Office Médico-Pédagogique, Department of Psychiatry, University of Geneva, Rue David-Dufour 1, Case Postale 50, 1211 Genève 8, Switzerland.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Padula
authors.affiliation: Office Médico-Pédagogique, Department of Psychiatry, University of Geneva, Rue David-Dufour 1, Case Postale 50, 1211 Genève 8, Switzerland ; Stanford Cognitive and Systems Neuroscience Laboratory, Stanford University, Stanford, CA USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Schaer
authors.affiliation: Office Médico-Pédagogique, Department of Psychiatry, University of Geneva, Rue David-Dufour 1, Case Postale 50, 1211 Genève 8, Switzerland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Scariati
authors.affiliation: Office Médico-Pédagogique, Department of Psychiatry, University of Geneva, Rue David-Dufour 1, Case Postale 50, 1211 Genève 8, Switzerland.
authors.forename: Maude
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland ; Medical Image Processing Lab, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Van De Ville
authors.affiliation: Office Médico-Pédagogique, Department of Psychiatry, University of Geneva, Rue David-Dufour 1, Case Postale 50, 1211 Genève 8, Switzerland ; Adolescence Clinical Psychology Research Unit, Faculty of Psychology and Educational Sciences, Geneva, Switzerland ; Research Department of Clinical, Educational and Health Psychology, University College London, London, U K.
authors.forename: Martin
authors.initials: M
authors.lastname: Debbané
authors.affiliation: Office Médico-Pédagogique, Department of Psychiatry, University of Geneva, Rue David-Dufour 1, Case Postale 50, 1211 Genève 8, Switzerland ; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Eliez
keywords: DTI; Maturation; Positive symptoms; Resting-state fMRI; Schizophrenia; Tractography