Investigations at St. Jude Children’s Research Hospital
Investigations at St. Jude Children’s Research Hospital have unveiled a heretofore-unknown link between the formation of the skull and increased susceptibility to schizophrenia. The research, disclosed in Nature Communications, intimates that the irregularities in the skull that occur in sync with 22q11.2 deletion syndrome (commonly referred to as 22q), may lead to atypical development of the cerebellum on account of the Tbx1 gene’s absence. This discovery introduces an innovative angle on the etiology of schizophrenia.
22q considerably heightens the probability of someone developing schizophrenia, a condition that materializes in nearly one-third of individuals diagnosed with the syndrome. In models of 22q and flesh-and-blood patients alike, scientists identified malformations in the cerebellar regions, mainly the flocculus and paraflocculus, suggesting that flawed cranial formation might be the impetus. Because of its vast conserved genomic expanse, the syndrome is an exemplary genetic archetype for the study of schizophrenia.
Cranial Alterations Affecting Cerebellar Performance
The cerebellum’s lobules must form within the contours of cranial spaces, but disruptions to osteoblast progression, caused by the missing Tbx1 gene, result in anomalies of the skull. Consequently, critical brain areas are diminished in size, affecting their operational capacity. MRI studies lend weight to this finding by showcasing disparities between individuals with 22q and a control group.
Beyond its established role in regulating movement, the cerebellum is integral to maintaining visual stability and recognizing faces — abilities that are diminished in individuals with 22q. This observation raises the prospect of a connection to the parallel impairments noted in schizophrenia cases.
Dr. Stanislav Zakharenko, part of St. Jude’s Department of Developmental Neurobiology, highlights the significance of these findings, stating that the neural architecture within the cerebellum’s flocculus and paraflocculus is compromised. He intends to trace the full scope of events, from skeletal anomalies through to the cerebellum and auditory cortex, thereby mapping a direct correlation between the symptomatology of schizophrenia and its skeletal foundations.
Funded by the National Cancer Institute at the National Institutes of Health and by the American Lebanese Syrian Associated Charities, the study sets the stage for deeper exploration into how the Tbx1 gene, cranial malformations, and schizophrenia are interconnected. This line of inquiry could also illuminate the obscure “second hit” that triggers hallucinations in affected individuals.
