Mitochondrial Dysfunction & 22qDS Neuropsychiatric Disease
- The health of our brains relies on tiny structures within nearly every cell called mitochondria.
- The blood-brain barrier is a highly specialized system that protects the brain from harmful substances circulating in the bloodstream while allowing essential nutrients to pass through.
- Researchers at the University of Pennsylvania School of Veterinary Medicine and Children's Hospital of Philadelphia (CHOP) focused their investigation on 22q11.2 deletion syndrome (22qDS), also known as DiGeorge...
Mitochondrial Dysfunction and the Brain: A New Target for Neuropsychiatric Disorders
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The Brain’s Powerhouses and a Leaky Barrier
The health of our brains relies on tiny structures within nearly every cell called mitochondria. Frequently enough referred to as the “powerhouses of the cell,” mitochondria generate the energy needed for vital functions.Emerging research highlights their critical role not just in cellular energy production, but also in overall brain health and the prevention of neuropsychiatric disorders. A recent study, published on August 20, 2025, in Science Translational Medicine, reveals a potential link between mitochondrial dysfunction in the blood-brain barrier (BBB) and conditions like schizophrenia and psychosis.
The blood-brain barrier is a highly specialized system that protects the brain from harmful substances circulating in the bloodstream while allowing essential nutrients to pass through. Maintaining a healthy BBB is crucial for optimal brain function, and disruptions to its integrity have been implicated in a range of neurological and psychiatric illnesses, including autism, multiple sclerosis, and alzheimer’s disease.
Focus on 22qDS: A Genetic Window into Brain Health
Researchers at the University of Pennsylvania School of Veterinary Medicine and Children’s Hospital of Philadelphia (CHOP) focused their investigation on 22q11.2 deletion syndrome (22qDS), also known as DiGeorge syndrome. This genetic condition, affecting six mitochondrial genes, significantly increases the risk of neurodevelopmental and neurodegenerative diseases. Individuals with 22qDS face a staggering 25-fold higher risk of developing psychosis, and approximately one in four will develop schizophrenia.
CHOP boasts the world’s largest clinic dedicated to the care of individuals with 22qDS, providing a unique resource for researchers seeking to understand the underlying causes of these complex conditions. The collaborative effort between Penn and CHOP aims to unlock the mysteries of neurodevelopmental disease by studying 22qDS as a model.
A “Leaky” Barrier and the Role of Mitochondria
The study revealed that the BBB is compromised in individuals with 22qDS, suggesting impaired communication between the brain and the rest of the body.Researchers discovered evidence of mitochondrial deficits contributing to this dysfunction. Specifically, they observed signs of a “leaky” BBB in both human cells derived from patients with 22qDS and in preclinical models of the syndrome.
“We previously established that the BBB is compromised in 22qDS, indicating that the crosstalk between the brain and the periphery can be affected. With these findings in mind, we addressed the hypothesis that mitochondrial deficits contribute to BBB dysfunction in 22qDS.”
Repurposing Cholesterol Drugs for Brain Health?
In a particularly encouraging finding, the researchers found that bezafibrate, an FDA-approved cholesterol drug known to boost mitochondrial function and turnover, could improve BBB function in both cell-based and preclinical models of 22qDS. Moreover, treatment with bezafibrate in the preclinical model corrected deficits in social memory, a cognitive function frequently enough impaired in individuals with schizophrenia and linked to BBB dysfunction.
“This study really demonstrates the power of collaboration,” said Stewart A. Anderson, MD, Associate Chair for Research in the department of Child and Adolescent Psychiatry and Behavioral Sciences at CHOP and associate director of the CHOP/Penn Lifespan Brain Institute. “By combining our respective expertise on mitochondrial function and the BBB, we have made an important revelation that may substantially help individuals with 22qDS.”
These results suggest that bezafibrate, or similar drugs, could potentially be repurposed as a treatment for BBB dysfunction and related neuropsychiatric symptoms. However, further research, including clinical trials, is necessary to confirm these findings and assess the safety and efficacy of this approach.
Beyond 22qDS: Implications for a Wider Range of Conditions
While this study focused specifically on 22qDS, the researchers believe their findings have broader implications. Mitochondrial dysfunction in the BBB may be a common underlying factor in a variety of neuropsychiatric conditions, opening up new avenues for therapeutic intervention. The potential to target mitochondrial function to improve BBB integrity could offer a novel approach to treating conditions ranging from autism to Alzheimer’s disease.