Dataset Information

A Comprehensive Analysis of Cerebellar Volumes in the 22q11.2 Deletion Syndrome.

ABSTRACT:

Background

The presence of a 22q11.2 microdeletion (22q11.2 deletion syndrome [22q11DS]) ranks among the greatest known genetic risk factors for the development of psychotic disorders. There is emerging evidence that the cerebellum is important in the pathophysiology of psychosis. However, there is currently limited information on cerebellar neuroanatomy in 22q11DS specifically.

Methods

High-resolution 3T magnetic resonance imaging was acquired in 79 individuals with 22q11DS and 70 typically developing control subjects (N = 149). Lobar and lobule-level cerebellar volumes were estimated using validated automated segmentation algorithms, and subsequently group differences were compared. Hierarchical clustering, principal component analysis, and graph theoretical models were used to explore intercerebellar relationships. Cerebrocerebellar structural connectivity with cortical thickness was examined via linear regression models.

Results

Individuals with 22q11DS had, on average, 17.3% smaller total cerebellar volumes relative to typically developing subjects (p < .0001). The lobules of the superior posterior cerebellum (e.g., VII and VIII) were particularly affected in 22q11DS. However, all cerebellar lobules were significantly smaller, even after adjusting for total brain volumes (all cerebellar lobules p < .0002). The superior posterior lobule was disproportionately associated with cortical thickness in the frontal lobes and cingulate cortex, brain regions known be affected in 22q11DS. Exploratory analyses suggested that the superior posterior lobule, particularly Crus I, may be associated with psychotic symptoms in 22q11DS.

Conclusions

The cerebellum is a critical but understudied component of the 22q11DS neuroendophenotype.

SUBMITTER: Schmitt JE

PROVIDER: S-EPMC9162086 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

A Comprehensive Analysis of Cerebellar Volumes in the 22q11.2 Deletion Syndrome.

Schmitt J Eric JE DeBevits John J JJ Roalf David R DR Ruparel Kosha K Gallagher R Sean RS Gur Ruben C RC Alexander-Bloch Aaron A Eom Tae-Yeon TY Alam Shahinur S Steinberg Jeffrey J Akers Walter W Khairy Khaled K Crowley T Blaine TB Emanuel Beverly B Zakharenko Stanislav S SS McDonald-McGinn Donna M DM Gur Raquel E RE

Biological psychiatry. Cognitive neuroscience and neuroimaging 20211127 1

<h4>Background</h4>The presence of a 22q11.2 microdeletion (22q11.2 deletion syndrome [22q11DS]) ranks among the greatest known genetic risk factors for the development of psychotic disorders. There is emerging evidence that the cerebellum is important in the pathophysiology of psychosis. However, there is currently limited information on cerebellar neuroanatomy in 22q11DS specifically.<h4>Methods</h4>High-resolution 3T magnetic resonance imaging was acquired in 79 individuals with 22q11DS and 7 ...[more]

PMID: 34848384

Similar Datasets

Project description:22q11.2 deletion syndrome is characterised by a well defined microdeletion that is associated with a high risk of neuropsychiatric disorders, including intellectual disability, schizophrenia, attention-deficit hyperactivity disorder, autism spectrum disorder, anxiety disorders, seizures and epilepsy, and early-onset Parkinson's disease. Preclinical and clinical data reveal substantial variability of the neuropsychiatric phenotype despite the shared underlying deletion in this genetic model. Factors that might explain this variability include genetic background effects, additional rare pathogenic variants, and potential regulatory functions of some genes in the 22q11.2 deletion region. These factors might also be relevant to the pathophysiology of these neuropsychiatric disorders in the general population. We review studies that might provide insight into pathophysiological mechanisms underlying the expression of neuropsychiatric disorders in 22q11.2 deletion syndrome, and potential implications for these common disorders in the general (non-deleted) population. The recurrent hemizygous 22q11.2 deletion, associated with 22q11.2 deletion syndrome, has attracted attention as a genetic model for common neuropsychiatric disorders because of its association with substantially increased risk of such disorders.1 Studying such a model has many advantages. First, 22q11.2 deletion has been genetically well characterised.2 Second, most genes present in the region typically deleted at the 22q11.2 locus are expressed in the brain.3-5 Third, genetic diagnosis might be made early in life, long before recognisable neuropsychiatric disorders have emerged. Thus, this genetic condition offers a unique opportunity for early intervention, and monitoring individuals with 22q11.2 deletion syndrome throughout life could provide important information on factors contributing to disease risk and protection. Despite the commonly deleted region being shared by about 90% of individuals with 22q11.2 deletion syndrome, neuropsychiatric outcomes are highly variable between individuals and across the lifespan. A clear link remains to be established between genotype and phenotype.3,5 In this Review, we summarise preclinical and clinical studies investigating biological mechanisms in 22q11.2 deletion syndrome, with a focus on those that might provide insight into mechanisms underlying neuropsychiatric disorders in 22q11.2 deletion syndrome and in the general population.

Dataset Information

A Comprehensive Analysis of Cerebellar Volumes in the 22q11.2 Deletion Syndrome.

Background

Methods

Results

Conclusions

Publications

A Comprehensive Analysis of Cerebellar Volumes in the 22q11.2 Deletion Syndrome.

Similar Datasets

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