youth

Changes in brain connectivity before and after puberty may explain why some children with rare genetic disorders are at a higher risk of autism or schizophrenia, according to UCLA Health Research.

Developmental mental illnesses such as autism and schizophrenia are associated with changes in brain function connectivity. However, the complexity of these conditions makes it difficult to understand potential biological reasons. By studying genetically defined brain diseases, UCLA Health researchers and collaborators have revealed possible mechanisms. “

The UCLA study examined a specific genetic disease called 22q11.2 chromosome chromosome syndrome, which is caused by the lack of DNA on chromosome 22, which is associated with a higher risk of developing neuropsychiatric diseases such as autism and schizophrenia. However, the basic biological basis of this association has not been fully understood.

In a recent study published in the journal Science Advances, researchers used functional brain imaging in both mice and humans to study the underlying mechanisms that drive the link between genetic mutations and the development of neuropsychiatric diseases.

Functional brain imaging shows that the brain exceeds the connection between genetically modified brain regions before puberty, before puberty, especially after puberty, especially in brain regions related to social skills and autism.

Carie Bearden, a professor at UCLA Health Semel Institute and UCLA Brain Institute, said changes in synaptic levels appear to explain the sudden transfer of connectivity and the related effects on social behavior.

“The differences in functional connectivity observed on MRI are often found in mental illness, but we are really valuable for why we should study this phenomenon,” Bearden said.

Bearden and colleagues at the Italian Institute of Technology used genetically modified mouse 22Q11.2 deletion syndrome and found that young mice had a higher dendritic spine density – compared to other neurons, small protrusions on brain cells compared to other neurons compared to other neurons. After mice reached the same level of puberty, the number of dendritic spines decreased dramatically compared with wild-type mice.

The protein GSK3-β, which is involved in synaptic regulation, may play a role in connectivity changes. Bearden and her collaborators used drugs to inhibit GSK3-β, an antibody that temporarily restored brain activity and dendritic spine density in mice, possibly restored brain activity and dendritic shape by modulating the removal of dendritic spines. Human brain imaging also found that brain regions affected by connectivity changes are enriched with genes associated with GSK3-β. Furthermore, changes in brain connectivity are associated with human social behavior, suggesting that altered wiring contributes to autistic traits.

Bearden said these findings suggest that synaptic dysfunction drives changes in brain activity and may be the target of preventing or reducing symptoms caused by the 22q11.2 chromosome-lowering syndrome.

“These findings strongly suggest that excessive synaptic hypersensitivity during development may lead to the behavioral challenges we see,” Bearden said.

The study was co-led by Alessandro Gozzi of Istituto di tecnologia, Italy’s Royal Istilla.