A Novel Connection: Cranial Development and Onset of Schizophrenia
A team of scientists at St. Jude Children’s Research Hospital uncovered an unexpected mechanism that could initiate schizophrenia — a developmental process driven by the Tbx1 gene that affects the skull’s structure. These groundbreaking insights suggest that factors outside the brain, such as the way bones form, play a critical role in the emergence of mental health disorders, especially in patients with the genetic anomaly known as 22q11.2 deletion syndrome.
Impact of Gene Disruption on Neurological Formation
Individuals with 22q face an elevated risk for developing schizophrenia and are more likely to have abnormalities in the cerebellum, the brain area tasked with the integration of sensory perception and coordination. The investigative team at St. Jude’s observed these irregularities in the cerebellum of 22q patients and in animal models with similar conditions. The anomalies linked to the syndrome were attributed to unusual developments in the skull, mainly affecting the brain spaces reserved for the cerebellum’s flocculus and paraflocculus areas.
Zakharenko, an MD and Ph.D. in St. Jude’s Department of Developmental Neurobiology, highlights, “Elimination of a singular gene from 22q, Dgcr8, hinders the auditory information path, potentially echoing the auditory hallucinations symptomatic of schizophrenia.” He proposes this represents one “hit” towards the disorder but assumes another hit exists given the ephemeral nature of such hallucinations.
Unexpectedly, Tbx1 doesn’t appear to have a direct correlation with brain development. Zakharenko clarifies, “Its expression occurs within the neighboring tissues, including bone, cartilage, and the blood vessel network. It’s improbable that Tbx1 plays a direct role in influencing the brain.” The lack of Tbx1 impairs the bone cell development process, leading to a deformed skull lacking the proper accommodations for the full growth of certain cerebellar structures, thereby resulting in their diminution.
Pathogenesis of Schizophrenia
Neuroscientists have determined functional issues within the neural pathways of the flocculus and paraflocculus. These specific cerebellar regions are integral for maintaining visual stability during head motion and are critical for recognizing faces, a capability often hindered in individuals with schizophrenia.
These discoveries also propose a linkage between cerebellar malformations and irregularity in the auditory cortex, which may shed more light on the origins of auditory hallucinations. “We’re eager to map the progression from the malformed skull to the undergrown cerebellum area and then to the dysfunction of the auditory cortex,” says Zakharenko. “It would be notable, considering it originated from a discrepancy in bone formation.”
Published in Nature Communications, this study, supported by the National Cancer Institute at the National Institutes of Health and the American Lebanese Syrian Associated Charities, paves the path for a novel understanding and potential treatment strategies for schizophrenia. It highlights a complex and previously unexpected relationship between bone formation and the intricate operations of the brain.
