Contact: Steven Lee, 210-450-3823, lees22@uthscsa.edu
Content by Claire Kowalik
SAN ANTONIO, December 5, 2024 – A study published in Molecular Psychiatry shows that changes in brain volume in psychiatric disorders such as autism spectrum disorder and schizophrenia correlate with differences in social behavior. It turns out.
The study, led by Noboru Hiroi, Ph.D., professor of pharmacy at the University of Texas at San Antonio Health Science Center (UT Health San Antonio), Joe R., and Teresa Lozano-Long, professor of medicine, found that specific genes were linked to social behavior in mice. It was related to the difference. Common differences in mental illness.
Genetic mutations are linked to some mental illnesses
Copy number variants (CNVs) are genetic changes in which a segment of a chromosome exhibits a deviation from its normal copy number. These genomic variations are increasingly recognized to have an impact on brain structure and to be associated with psychiatric disorders. CNVs often involve multiple genes, but how individual genes within these mutations specifically contribute to brain development and mental states remains largely unknown. .
One notable example is the 22q11.2 region of human chromosome 22, which contains more than 30 protein-coding genes. Among these, the Tbx1 gene has emerged as an important regulator of stem cell function in the brain, as highlighted in a previous study by Hiroi et al. Variants in Tbx1 are strongly associated with a variety of neurodevelopmental and psychiatric disorders, including autism spectrum disorder, schizophrenia, intellectual disability, and developmental delay. Understanding the role of Tbx1 and other genes within this region is essential for elucidating the mechanisms underlying CNV-associated brain abnormalities and psychiatric outcomes.
“Professor Dr. Hiroi’s pioneering research in the Department of Pharmacology has significantly advanced our understanding of the genetic basis of psychiatric disorders such as autism spectrum disorder and schizophrenia,” said Dr. Long School of Medicine, University of Utah. said Dr. Daniel Lodge, professor and head of the Department of Pharmacology. San Antonio Health. “His recent work on Tbx1 not only highlights the complexity of gene-phenotype interactions, but also how precise volumetric analysis can elucidate the neural correlates of behavioral disorders and inform potential therapeutic interventions.” It shows how you can pave the way.”
Differences in brain volume
For this study, the research team created mice lacking the Tbx1 gene and used volumetric MRI analysis to examine differences in brain volume in these mice compared to wild-type mice. They also assessed the social behavior of Tbx1-deficient mice compared to unmodified mice.
Professor Hiroi found that Tbx1-deficient mice had reduced volume in the amygdala and surrounding cortical regions, particularly in a mysterious small region of the amygdala called the amygdaloid transition region. Although the amygdala is an important region for the control of emotional behavior and is poorly understood, the amygdala piriform transition region is connected to many brain regions involved in processing sensory and emotional cues.
Desire for social interaction is affected
Animals and humans learn to use cues and context to determine whether social experiences have positive value, Hiroi said. Mice are social creatures, and when given the choice between being isolated or congregating with other mice, they tend to choose to socialize. In this study, wild-type and Tbx1-deficient mice were given a choice of two enclosures: one with another mouse and one without. Wild-type mice always chose an enclosure containing another mouse, but Tbx1-deficient mice were ambiguous about whether another mouse was present and chose their location based on other cues, such as where their preferred type of bedding was located. .
“This study suggests that Tbx1 deficiency may contribute to humans’ ability to assess the positive incentive value of social experiences,” Professor Hiroi said.
What comes next?
Professor Hiroi teamed up with Dr. Jason Pugh of the UT Health San Antonio Department of Cellular and Integrative Physiology to take his research a step further by examining the excitability of specific neuron types in the amygdaloid transition region of Tbx1-deficient mice. Masu. . They are also working to develop a model that can initiate and restore Tbx1 heterozygosity (having two versions of the same gene) at any stage of development. Professor Hiroi said that once completed, the model will be used to discover key developmental periods for amygdala shrinkage.
Professor Hiroi said that amygdala volume loss appears to occur during fetal life, and therapeutic interventions could target this point. Furthermore, the degree of amygdala reduction may be a biomarker of impaired recognition of social experiences in people with autism spectrum disorders and schizophrenia.
“This research has the potential to serve as a catalyst to translationally link basic science with human brain imaging research and research on patients with neurodevelopmental disorders, which is already a major strength at UT Health San Antonio,” Hiroi said. the professor said.
Other authors of Hiroi’s Tbx1 study are also affiliated with the UT Health San Antonio College of Pharmacy and the Tohoku University Institute on Aging, Sendai. Human-Animal Interaction and Reciprocity Laboratory, National Institutes for Quantum and Radiological Science and Technology (Chiba Prefecture), Azabu University (Sagamihara City, Kanagawa Prefecture).
UT Health San Antonio is a world-class research university, ranked in the top 5% of institutions worldwide for clinical medicine according to U.S. News & World Report. The university ranks 12th in the world among universities in terms of the impact of its discoveries. Standardized citation impact, which compares the number of citations a study receives per paper to the average of similar published papers, is recognized as a central measure of research impact.
Highly circumscribed structural changes in the brain and impaired social incentive learning in Tbx1 heterozygous mice
Takeshi Hiramoto, Akira Sumiyoshi, Risa Kato, Ryuhei Yamauchi, Takeshi Takano, Gina Kang, Marisa Esparza, Bailey Matsumura, Lucas J. Stevens, Yukiko J. Hiroi, Takaki Tanifuji, Rie Ryoke, Hiroi Nonaka, Machida Akihiro, Kensaku Nomoto, Mogi Kazutaka, Takefumi Kikusui, Ryuta Kawashima, Noboru Hiroi
First publication date: October 27, 2024, Molecular Psychiatry
Link to full study: https://www.nature.com/articles/s41380-024-02797-x?utm_source=rct_congratemailt&utm_medium=email&utm_campaign=oa_20241028&utm_content=10.1038/s41380-024-02797-x
The University of Texas at San Antonio Health Science Center (UT Health San Antonio) is a major driver of San Antonio’s $44.1 billion health care and bioscience sector, with an annual research portfolio of $413 million in South Texas. It is the largest academic research institution. With six professional schools, more than 8,500 diverse employees, an annual expense budget of $1.46 billion, and clinical operations that provide 2.6 million patient visits each year, UT drives significant economic impact. Health San Antonio plans to add more than 1,500 high-paying employees. Jobs will be added over the next five years to serve San Antonio, Bexar County and South Texas. Visit UTHealthSA.org to learn more about how we make lives better®.
UT Health San Antonio Joe R. and Teresa Lozano Long School of Medicine is named among U.S. News & World Report’s Best Medical Schools and ranks in the top 30% nationally for research. For more information, please visit https://uthscsa.edu/medicine/.
Stay connected with The University of Texas Health Science Center at San Antonio on Facebook, Twitter, LinkedIn, Instagram and YouTube.
