Groundbreaking Research Links Puberty to Psychiatric Disorders

A striking new study from UCLA Health reveals that pivotal shifts in brain connectivity before and after puberty could shed light on why children with a rare genetic disorder have a higher risk of developing autism and schizophrenia.

Understanding the Complexities Behind Disorders

Developmental psychiatric disorders like autism and schizophrenia are characterized by notable changes in how regions of the brain communicate. However, the intricate nature of these conditions has long puzzled researchers trying to pinpoint their biological triggers. By exploring genetically defined brain disorders, scientists at UCLA Health have begun to unravel these mysteries.

Zooming In on Chromosome 22q11.2 Deletion Syndrome

The study specifically focused on chromosome 22q11.2 deletion syndrome, a condition where critical DNA segments on chromosome 22 are missing. This genetic anomaly is linked with an elevated risk of developing neuropsychiatric disorders, yet the precise biological mechanisms at play have remained largely unexplored.

Innovative Imaging Techniques Reveal Surprising Results

Published in the journal *Science Advances*, the study employed advanced brain imaging techniques in both humans and genetically altered mice. Remarkably, the findings revealed that brain regions were hyperconnected before puberty but became under-connected afterward, particularly those areas crucial for social skills and autism.

A Closer Look: The Role of Synaptic Changes

Carrie Bearden, co-senior author and a professor at UCLA’s Semel Institute, pointed out that alterations at the synaptic level may explain this odd shift in connectivity and its effects on social behavior. "The differences in functional connectivity we see on MRIs are commonplace in psychiatric disorders, but the reasons behind them remain elusive. Studying this phenomenon across species proved invaluable," Bearden explained.

Mice Models Shine Light on Synaptic Density

The researchers found that genetically modified mice mimicking the syndrome exhibited a higher density of dendritic spines—tiny structures on brain cells that facilitate communication—during childhood. However, post-puberty, these spines dramatically decreased compared to their normal counterparts.

The Protein Connection: GSK3-beta

Intriguingly, the protein GSK3-beta, known for its role in synapse regulation, seems to be involved in these connectivity changes. Using a specialized drug, researchers temporarily inhibited GSK3-beta, leading to a restoration of brain activity and dendritic spine density in the mice, suggesting a potential avenue for therapeutic intervention.

Implications for Humans and Future Treatments

In human subjects with the condition, similar brain regions showed connectivity changes associated with genes linked to GSK3-beta. These alterations were also tied to social behavior, indicating that the rewiring of these circuits may underlie traits of autism.

Bearden emphasizes that these discoveries highlight how synaptic dysfunction may catalyze shifts in brain activity, opening up new possibilities for treatments aimed at alleviating symptoms associated with chromosome 22q11.2 deletion syndrome.

A New Hope for Preventative Measures

"These findings strongly suggest that excessive pruning of synapses during crucial developmental stages could contribute to the behavioral challenges we see," Bearden concluded, hinting at a hopeful pathway for future interventions.

Further Reading

Reference: Alvino FG, Gini S, Minetti A, et al. Synaptic-dependent developmental dysconnectivity in 22q11.2 deletion syndrome. *Sci Adv*. 11(11):eadq2807. doi: 10.1126/sciadv.adq2807.