Abstract
BackgroundThe 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.MethodsT1-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.ResultsA 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.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-015-9120-y) contains supplementary material, which is available to authorized users.
Highlights
The neural endophenotype associated with 22q11.2 deletion syndrome (22q11DS) includes deviant cortical development and alterations in brain connectivity
Considering the normal development of white matter in healthy people [61, 62], we investigated if structural and functional connectivity measures increased with age in our group of control and 22q11DS participants
To further establish if alterations in the default mode network (DMN) connectivity were associated with early symptoms of psychosis in 22q11DS, we investigated the relationship between structural and functional DMN connectivity and the Structured Interview of Prodromal Syndromes (SIPS, [64]) positive scores
Summary
The neural endophenotype associated with 22q11.2 deletion syndrome (22q11DS) includes deviant cortical development and alterations in brain connectivity. 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. Chromosome 22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental disorder associated with a broad phenotypic expression including clinical, cognitive, and psychiatric manifestations [1]. Functional networks undergo similar processes of integration and specialization [13,14,15]. These maturation processes are altered in neurodevelopmental and psychiatric disorders [16,17,18], resulting in the onset of cognitive, behavioral, and psychological impairments
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