White matter microstructure in 22q11 deletion syndrome: a pilot diffusion tensor imaging and voxel-based morphometry study of children and adolescents

Abstract

Young people with 22q11 Deletion Syndrome (22q11DS) are at substantial risk for developing psychosis and have significant differences in white matter (WM) volume. However, there are few in vivo studies of both WM microstructural integrity (as measured using Diffusion Tensor (DT)-MRI) and WM volume in the same individual. We used DT-MRI and structural MRI (sMRI) with voxel based morphometry (VBM) to compare, respectively, the fractional anisotropy (FA) and WM volume of 11 children and adolescents with 22q11DS and 12 controls. Also, within 22q11DS we related differences in WM to severity of schizotypy, and polymorphism of the catechol-O-methyltransferase (COMT) gene. People with 22q11DS had significantly lower FA in inter-hemispheric and brainstem and frontal, parietal and temporal lobe regions after covarying for IQ. Significant WM volumetric increases were found in the internal capsule, anterior brainstem and frontal and occipital lobes. There was a significant negative correlation between increased schizotypy scores and reduced WM FA in the right posterior limb of internal capsule and the right body and left splenium of corpus callosum. Finally, the Val allele of COMT was associated with a significant reduction in both FA and volume of WM in the frontal lobes, cingulum and corpus callosum. Young people with 22q11DS have significant differences in both WM microstructure and volume. Also, there is preliminary evidence that within 22q11DS, some regional differences in FA are associated with allelic variation in COMT and may perhaps also be associated with schizotypy.

Large-scale functional network reorganization in 22q11.2 deletion syndrome revealed by modularity analysis

“…Both pathways are thought to be impaired in patients with the microdeletion as deficits in visuo-spatial skills (Antshel et al, 2008), face recognition (Andersson et al, 2008;Lajiness-O'Neill et al, 2005) and social skills (Baker & Vorstman, 2012;Baker & Skuse, 2005) have been consistently described in 22q11DS. Furthermore, functional connectivity alterations of high-level visual networks had already been identified in our former ICA study , and abnormal white matter structure in parietal regions have been described in DTI studies including both with increased (da Silva Alves et al, 2011;Simon et al, 2005Simon et al, , 2008 and decreased (Barnea-Goraly et al, 2003Sundram et al, 2010) fractional anisotropy. Here, we provide further evidence for early functional dysconnectivity of visual processing pathways in 22q11DS using a larger sample size and a different methodology.…”

“…Indeed, diffusion tensor imaging (DTI) studies [reviewed in (Gothelf, Schaer, & Eliez, 2008)] have reported relationships between microstructural irregularities of the white matter tracts and cognitive symptoms including arithmetic difficulties, and deficits in attention and social capacities (Barnea-Goraly, Eliez, Menon, Bammer, & Reiss, 2005;Radoeva et al, 2012;Simon et al, 2008). Similar alterations have been associated with the intensity of schizotypal traits (Sundram et al, 2010) and psychotic symptoms (Jalbrzikowski et al, 2014;Radoeva et al, 2012).…”

Identifying 22q11.2 Deletion Syndrome and Psychosis Using Resting-State Connectivity Patterns

“…Although these discriminative connections were widespread, functional connectivity of the frontal lobe played an important role in classification. Several studies using DTI have already identified a widespread alteration of the structural brain network in 22q11DS (Barnea-Goraly et al 2003;Simon et al 2005;Sundram et al 2010;Radoeva et al 2012) that also affect tracts originating from the frontal lobe (Simon et al 2008;Barnea-Goraly et al 2003;Radoeva et al 2012). This has been further confirmed by a recent tractographic study showing alterations in the number of reconstructed fibers in several brain lobes, including the frontal lobes (Ottet et al 2013a).…”

“…Apart from the somatic consequences of this deletion, the disorder is characterized by a high incidence of cognitive and psychiatric disabilities (Baker and Vorstman 2012), including notably a mild decrease in IQ (Antshel et al 2008a) and a high prevalence of psychotic symptoms (Baker and Skuse 2005) and schizophrenia (Murphy et al 1999). In this disorder, structural alterations of the brain networks are sustained by white matter alterations including a well described 11-16 % loss of volume (Simon et al 2005;Eliez et al 2000) and widespread microstructural defects (Sundram et al 2010;Barnea-Goraly et al 2003;da Silva et al 2011;Simon et al 2008) that have furthermore been associated to various cognitive deficiencies (Radoeva et al 2012;Barnea-Goraly et al 2005;Simon et al 2008) and psychiatric symptoms (Radoeva et al 2012) including schizotypal traits (Sundram et al 2010). The alteration of the structural wiring of the brain in 22q11DS has recently been confirmed using tractography (Ottet et al 2013a).…”

Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome

“…First, based on prior work (Sundram et al, 2010; Radoeva et al, 2012), we expected to find lower FA in long-range fiber tracts in 22q11DS relative to controls, including the SLF and uncinate fasciculus, which would be driven by abnormal AD (Kikinis et al, 2012; Radoeva et al, 2012). Based on previous literature in CHR youth and 22q11DS (Karlsgodt et al, 2009; Ottet et al, 2013a), we hypothesized that 22q11DS youth would fail to show the typical age-associated increases in FA observed in typically developing controls (Simmonds et al, 2014).…”