Mitochondrial Dysfunction Found as Key Contributor to Schizophrenia Development
Researchers at Rutgers University and Emory University have made significant progress in understanding the development of schizophrenia by examining a genetic risk factor associated with the disease. The risk of developing schizophrenia is increased by nearly 40 times when a tiny piece of chromosome 3 is missing, known as 3q29 deletion syndrome. Through the use of CRIPSR and human brain organoids, scientists have analyzed patterns of altered gene activity in models of the 3q29 deletion syndrome and found that both systems exhibited deteriorated mitochondrial activity.
Mitochondria, which are present in every cell, are responsible for producing energy from sugar or fat. The researchers discovered that the brains of individuals with 3q29 deletion syndrome experienced energy shortages due to mitochondrial dysfunction. This shortage may manifest as psychiatric symptoms and diseases linked to schizophrenia. By establishing the connection between mitochondrial dysregulation and the development of schizophrenia, this study provides robust support for the hypothesis.
Jennifer Mulle, Associate Professor at Rutgers Robert Wood Johnson Medical School, emphasizes the significance of the interplay between mitochondrial dynamics and neuronal maturation in the development of schizophrenia. The study’s findings align with previous research on another genetic risk factor for schizophrenia, known as 22q11 deletion syndrome or DiGeorge syndrome, which also involves disrupted mitochondrial function.
While the role of individual genes within the 3q29 deletion is still being unraveled, it is noteworthy that various chromosomal deletions associated with schizophrenia impair mitochondrial function. This challenges the expectation that these mutations would affect proteins in the synapses that connect neurons. However, since mitochondria are critical for synapse function, these models are not in conflict.
Surprisingly, only one of the 22 genes in the 3q29 deletion appears to encode a protein located in mitochondria, yet the researchers speculate that other genes within the interval may regulate the production or importation of mitochondrial proteins. This could explain why cells with 3q29 deletion have poorly functioning mitochondria.
The effects of 3q29 deletion are not limited to the brain; they are also observed in kidney cells. Individuals with 3q29 deletion syndrome may experience intellectual disability, autism spectrum disorder, and congenital heart defects in addition to an increased risk of developing schizophrenia. Moreover, altered fat metabolism resulting from mitochondrial dysfunction may explain why individuals with the syndrome tend to be smaller in size.
The researchers hope that their findings will contribute to a deeper understanding of the cellular pathology underlying schizophrenia. Identifying cellular changes linked to specific clinical outcomes could greatly assist in the development of more effective therapeutic strategies. By investigating the impact of mitochondrial dysregulation and its subsequent energy shortages on neuronal development, the researchers aim to unravel the neurobiology of schizophrenia further.
The study sheds light on the complex nature of schizophrenia, a condition that affects millions worldwide. As scientists continue to explore the interplay between genetics and mitochondrial function, these findings mark an important step toward unlocking the mysteries of schizophrenia and potentially developing targeted treatments to improve the lives of those affected.
