Hippocampal volume reduction in children with chromosome 22q11.2 deletion syndrome is associated with cognitive impairment
Open accessAbstract
BACKGROUND: Previous 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. METHOD: A 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. RESULTS: Volumetric 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). CONCLUSION: Results 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.
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Imaging studies in 22q11.2 syndrome have revealed smaller brain volume, decreased cortical thickness in the superior parietal, right parietooccipital and inferior frontal gyrus, heterotopias and fewer gyri, and reduced volume in the hippocampus, cerebellum and amygdala, some of which varies based on the presence of schizophrenia or cognitive deficits.
“Imaging studies in 22q11.2 syndrome have revealed smaller brain volume [361], decreased cortical thickness in the superior parietal, right parietooccipital and inferior frontal gyrus, heterotopias and fewer gyri [27, 193, 314], and reduced volume in the hippocampus [84, 85], cerebellum [49] and amygdala [85], some of which varies based on the presence of schizophrenia or cognitive deficits [20, 31”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [85]
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- Authors
- DeBoer, T., Wu, Z., Lee, A., & Simon, T. J.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- DeBoer, Tracy
- Venue
- Behavioral and Brain Functions
- Published
- 2007
- Volume
- 3
- Issue
- 1
- Pages
- 54
- ISSN
- 1744-9081 (ISSN-L)
- PMC
- PMC2173902
- OpenAlex
- W2158785511
- Cited by
- 67
- References
- 42
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 2
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Behavioral and Brain Functions (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University Libraries (University of Maryland) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (T32MH073124)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD042974, R01HD046159)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- hippocampal volume, cognitive impairment, intellectual disability, amygdala, temporal lobe, gray matter, white matter, brain volumetry, children, neuroanatomy
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