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

J. Eric Schmitt, John J. DeBevits, David R. Roalf, Kosha Ruparel, R. Sean Gallagher, Ruben C. Gur, Aaron Alexander-Bloch, Tae Yeon Eom, Shahinur Alam, Jeffrey Steinberg, Walter Akers, Khaled Khairy, T. Blaine Crowley, Beverly Emanuel, Stanislav S. Zakharenko, Donna M. McDonald-McGinn, Raquel E. Gur

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)79-90
Number of pages12
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number1
StatePublished - Jan 2023


  • 22q11.2 deletion syndrome
  • Cerebellum
  • Crus I
  • Genetics
  • MRI
  • Psychosis
  • Schizophrenia

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Cognitive Neuroscience
  • Radiology Nuclear Medicine and imaging


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