A comprehensive analysis of cerebellar volumes in the 22q11.2 Deletion Syndrome

Published:November 27, 2021DOI:https://doi.org/10.1016/j.bpsc.2021.11.008

      Abstract:

      Background

      The presence of a 22q11.2 microdeletion (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 MRI was acquired in seventy-nine individuals with 22q11DS and seventy typically developing (TD) controls (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 inter-cerebellar relationships. Cerebro-cerebellar 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 TD (p-value<0.0001). 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 lobule p-values <0.0002). The superior posterior lobule (SPL) was disproportionately associated with cortical thickness in the frontal lobes and cingulate cortex, brain regions known be affected in 22q11DS. Exploratory analyses suggested that SPL, particularly Crus I, may be associated with psychotic symptoms in 22q11DS.

      Conclusions

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

      Key Words

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