Study Finds Gene Deficiency Linked to Brain Volume and Social Behavior in Autism and Schizophrenia
A recent study published in Molecular Psychiatry has revealed a connection between brain volume changes and social behavior differences in psychiatric conditions like autism spectrum disorder and schizophrenia. The research, led by Dr. Noboru Hiroi at UT Health San Antonio, focused on the Tbx1 gene and its impact on social behavior in mice. The study showed that a deficiency in Tbx1 led to shrinkage in the amygdala, a brain region critical for emotion processing and social behavior. This shrinkage was linked to impairments in social incentive evaluation, a behavior commonly observed in both autism and schizophrenia.
Genetic Variants and Their Link to Psychiatric Disorders
The study also delves into the role of copy number variants (CNVs), genetic changes where parts of chromosomes show an abnormal number of copies. These CNVs are increasingly understood to affect brain structure and contribute to psychiatric disorders. The Tbx1 gene, located in the 22q11.2 region of chromosome 22, is one such gene linked to a variety of neurodevelopmental and psychiatric disorders. Variants in Tbx1 are associated with autism, schizophrenia, intellectual disabilities, and developmental delays.
Dr. Hiroi’s work has contributed significantly to the understanding of how genes like Tbx1 regulate brain function and social behavior, potentially leading to new insights into therapeutic approaches for psychiatric conditions.
"Dr. Hiroi’s pioneering research has advanced our understanding of the genetic foundations of disorders such as autism and schizophrenia," said Daniel Lodge, Ph.D., Chair of the Department of Pharmacology at UT Health San Antonio. "This study highlights the importance of precise brain volumetric analyses in uncovering the neural mechanisms of behavioral impairments, opening doors for potential therapeutic interventions."
Study Finds Tbx1 Gene Deficiency Linked to Amygdala Volume Reduction and Social Behavior Changes
A new study has explored how the deficiency of the Tbx1 gene affects brain structure and behavior, particularly in relation to social interaction and emotional regulation. The research team, led by Dr. Noboru Hiroi, created mice lacking the Tbx1 gene and used volumetric MRI analysis to compare their brain volumes with those of wild-type mice. They also evaluated the social behaviors of these mice.
Brain Volume Differences
The study found that Tbx1-deficient mice had reduced brain volumes in areas associated with emotional regulation, most notably in the amygdala and its surrounding regions, including the amygdalo-piriform transition area. This small subregion of the amygdala, which is not well understood, plays a role in processing sensory and emotional cues. The amygdala is critical for emotional behavior regulation, and its shrinkage in these mice could shed light on the brain changes that contribute to psychiatric conditions.
Impact on Social Behavior
When given the choice between an enclosure with another mouse or an empty one, wild-type mice consistently chose to interact with the other mouse. However, Tbx1-deficient mice were ambivalent, selecting enclosures based on other factors, such as the type of bedding, rather than social cues. This suggests that Tbx1 deficiency impairs the ability to evaluate social experiences' positive value, which is a critical aspect of human and animal social behavior.
Next Steps in the Research
Dr. Hiroi is continuing the research by collaborating with Dr. Jason Pugh from the UT Health San Antonio Department of Cellular and Integrative Physiology to examine the excitability of neurons in the amygdalo-piriform transition area in Tbx1-deficient mice. They are also developing models that could restore Tbx1 expression at any point in development. This model will help identify the critical developmental window for amygdala shrinkage and guide potential therapeutic interventions.
Given that the reduction in amygdala volume appears to begin during embryonic development, Hiroi suggests that targeting this phase could help mitigate the effects. The degree of amygdala shrinkage could also serve as a potential biomarker for impairments in social interaction appreciation, particularly in conditions like autism spectrum disorder and schizophrenia.
“This study bridges basic science with human brain imaging and studies of neurodevelopmental disorders,” Hiroi remarked, emphasizing the potential for future applications in clinical settings at UT Health San Antonio.
