Hippocampal volume reduction in children with chromosome 22q11.2 deletion syndrome is associated with cognitive impairment

Abstract

BackgroundPrevious investigations of individuals with chromosome 22q11.2 deletion syndrome (DS22q11.2) have reported alterations in both brain anatomy and cognitive function. Neuroanatomical studies have reported multiple abnormalities including changes in both gray and white matter in the temporal lobe, including the amygdala and hippocampus. Separate investigations of cognitive abilities have established the prevalence of general intellectual impairment, although the actual extent to which a single individual is affected varies greatly within the population. The present study was designed to examine structures within the temporal lobe and assess their functional significance in terms of cognition in children with DS22q11.2.MethodA total of 72 children (ages 7–14 years) participated in the investigation: 36 children (19 female, 17 male) tested FISH positive for chromosome 22q11.2 deletion (Mean age = 10 years 9 months, ± 2 yr 4 mo) and 36 were age-matched typically developing controls (13 female, 23 male; Mean age = 10 years 6 months, ± 1 yr 11 mo). For each subject, a three-dimensional high-resolution (1 mm isotropic) T1-weighted structural MRI was acquired. Neuroanatomical guidelines were used to define borders of the amygdala and hippocampus bilaterally and volumes were calculated based on manual tracings of the regions. The Wechsler Intelligence Scale for Children (WISC) was also administered.ResultsVolumetric reductions in total gray matter, white matter, and both the amygdala and hippocampus bilaterally were observed in children with DS22q11.2. Reductions in the left hippocampus were disproportionate to decreases in gray matter after statistically controlling for group differences in total gray matter, age, and data collection site. This specific reduction in hippocampal volume was significantly correlated with performance on standardized measures of intelligence, whereas the other neuroanatomical measures were not (gray/white matter, CSF, and amygdala).ConclusionResults from this study not only contribute to the understanding of the neuroanatomical variation in DS22q11.2, but also provide insight into the nature and source of the cognitive impairments associated with the syndrome. Specifically, we report that decreases in hippocampal volume may serve as an index of severity for cognitive impairments in children with DS22q11.2.

The hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety

“…26 Second, we found a positive association between full-scale IQ and hippocampus volume across diagnoses, yet full-scale IQ did not relate to the local anatomy of the hippocampus. Previous studies demonstrated a positive association between hippocampal volume and IQ in typically developing children 67 and children with 22q11.2DS; 38 however, we have not replicated such an association. The specificity of the association between the hippocampus and IQ would be better evaluated in a more comprehensive study of total and regional brain volumes as well as white matter microstructure.…”

“…For children with 22q11.2DS, anxiety symptoms may in part be a result of abnormal modulation by the anterior hippocampus via direct pathways and indirectly via the vmPFC. This may be additive to abnormal anatomy 38,60 and hyperactivity of the amygdala. Further study of the amygdala and prefrontal structure and connectivity in the present data set would better inform this hypothesis.…”

“…38 When represented in 3-dimensional space, hippocampal volume and shape can be assessed at high resolution using a variety of methods. One validated method is localized components analysis (LoCA), which is a dimension reduction approach to shape analysis that outputs concise and spatially cohesive representations of the variance in structure across a sample.…”

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

“…The 22q11.2 deletion mouse model displayed several differences that mirrored what has been found in human 22q11.2 deletion syndrome [139][140][141]. Specifically, the larger striatum, smaller cerebellum, and smaller amygdala in the mouse model are all consistently found in human patients.…”

Cingulate gyral reductions are related to low executive functioning and psychotic symptoms in 22q11.2 deletion syndrome

“…Neuroimaging studies of 22q11DS describe how cerebral alterations in the syndrome relate to schizophrenia (Chow, Zipursky, Mikulis, & Bassett, 2002;Zinkstok & van Amelsvoort, 2005). Individuals with 22q11DS display general structural brain abnormalities, including reduced total brain tissue, grey and white matter volumes (Eliez, Schmitt, White, & Reiss, 2000;Kates et al, 2001), increased ventricular and basal ganglia volumes (Eliez, Barnea-Goraly, Schmitt, Liu, & Reiss, 2002), decreased thalamic, hippocampal as well amygdala volumes (Bish, Nguyen, Ding, Ferrante, & Simon, 2004;Debbané, Schaer, Farhoumand, Glaser, & Eliez, 2006;Deboer, Wu, Lee, & Simon, 2007), and a reduction in cingulate grey matter density (Simon et al, 2005). In schizophrenic 22q11DS subjects compared to nonschizophrenic, further anatomical differences include decreased whole-brain total volume and total white matter and increased total and sulcal cerebrospinal fluid volume (van Amelsvoort et al, 2004).…”