Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and voxel-based morphometry MRI study

Abstract

In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide spectrum of cognitive deficits ranging from global learning difficulties to specific cognitive deficits. People with 22qDS are also at high risk of developing attention-deficit/hyperactivity disorder and autism spectrum disorders in childhood, and schizophrenia in adolescence or adult life. However, the neurobiology of 22qDS, and the relationship between abnormalities in brain anatomy and behaviour, is poorly understood. Thus, we studied the neuroanatomy of 22qDS children using fully automated voxel-based morphometry (VBM) and manually traced single region-of-interest (ROI) analysis. Also, we investigated whether those brain regions that differed significantly between groups were related to behavioural differences within children with 22qDS. We compared the brain morphometry of 39 children and adolescents with 22qDS (mean age: 11 years, SD +/-3, IQ = 67, SD +/-10) and 26 sibling controls (mean age: 11 years, SD +/-3, IQ = 102, SD +/-12). Using VBM, we found, after correction for IQ, that individuals with 22qDS compared with controls had a significant reduction in cerebellar grey matter, and white matter reductions in the frontal lobe, cerebellum and internal capsule. Using single ROI analysis, we found that people with 22qDS had a significant (P < 0.05) reduction in bulk volume bilaterally in the occipital-parietal lobes, but a larger right caudate nucleus and lateral ventricles. Further, within people with 22qDS, there was a significant positive correlation between severity of (i) schizotypy score and grey matter volume of the temporo-occipital regions and the corpus striatum; (ii) emotional problems and grey matter volume of frontostriatal regions; and (iii) social behavioural difficulties and grey matter in frontostriatal regions. Thus, subjects with 22qDS have widespread changes in brain anatomy, particularly affecting white matter, basal ganglia and cerebellum. Also, within 22qDS, regionally specific differences in brain development may partially underpin behavioural differences. We suggest that there is preliminary evidence for specific vulnerability of the frontostriatal and cerebellar-cortical networks in 22qDS.

Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: A longitudinal study

“…Differences between the 22q11.2DS cohort studied here that were not detected in our previous analyses with smaller number of subjects included decreased occipital lobe and cerebellar GM and WM volumes. Decrease in volumes in the occipital lobe and cerebellum were reported in other studies of children with 22q11.2DS (Campbell et al, 2006;Simon et al, 2005).…”

“…Total brain volume is decreased by 8.5%-11% and there are extensive regional abnormalities in both gray matter (GM) and white matter (WM) volumes (Eliez et al, 2000;Kates et al, 2001;Simon et al, 2005). Frontal lobe grey and white matter volumes are relatively increased while posterior cortical regions including parietal and occipital grey and white matter volumes are reduced (Campbell et al, 2006;Eliez et al, 2000;Kates et al, 2001). In addition, there are aberrations of posterior fossa anatomy, most notably cerebellar grey and white matter volume reductions (Bish et al, 2006;.…”

“…In addition, there are aberrations of posterior fossa anatomy, most notably cerebellar grey and white matter volume reductions (Bish et al, 2006;. Abnormal volumes have also been reported for other brain regions, including enlarged volumes of ventricular cerebrospinal fluid (CSF), caudate nucleus, and amygdala (Campbell et al, 2006;Eliez et al, 2002;Kates et al, 2006;Simon et al, 2005).…”

“…However, since this is the first comparative longitudinal study of brain development in 22q11.2DS, we could not test hypotheses based on prior information about neurodevelopmental trajectories in this disorder. Accordingly, we chose to focus on the development of candidate brain regions that were previously reported to be abnormal in cross-sectional studies of both 22q11.2DS (Campbell et al, 2006;Chow et al, 2002;Eliez et al, 2002;Kates et al, 2006;Simon et al, 2005;van Amelsvoort et al, 2004) and schizophrenia (reviewed in (DeLisi et al, 2006;Shenton et al, 2001). Thus we analyzed change in volume of the cerebral lobes, superior temporal gyrus (STG), ventricular CSF, cerebellum, amygdala, hippocampus, and caudate nucleus.…”

Cortical mapping of genotype–phenotype relationships in schizophrenia

“…However, using quantitative measures, we previously found a relationship between reduced temporal gray matter and elevated Thought Problems, as assessed by the Child Behavior Checklist [Bearden et al, 2004]. Consistent with this, Campbell et al (2006) recently observed a significant positive correlation between severity of schizotypy score and gray matter volume in temporo-occipital regions and basal ganglia. Emotional and social problems were associated with gray matter volume in frontostriatal regions, suggesting that quantitative indices of psychopathology may be related to differences in brain development in this syndrome, even in the absence of categorical syndrome-based group differences.…”