Study shows how mitochondrial function impacts schizophrenia in patients with genetic disorder

An interdisciplinary team of researchers from (CHOP) and the University of Pennsylvania’s Perelman School of Medicine (Penn) demonstrated how cell “batteries” play a significant role in whether patients with the chromosomal 22q11.2 deletion syndrome acquire schizophrenia.

Schizophrenia. Image Credit: Lightspring/Shutterstock.com

The study findings might potentially lead to tailored prevention and treatment efforts for those suffering from the illness. The results were published in the journal JAMA Psychiatry.

22q11.2 deletion syndrome (22q) is a chromosomal difference that affects every system in the body, including the immune system, brain, developing heart, and palate. It affects around one out of every 2,000 infants and is linked with varying degrees of medical difficulties.

22q is also linked to behavioral health issues like autism spectrum disease, attention deficit hyperactivity disorder, and anxiety. These symptoms can be seen in children and can manifest as psychiatric disease in older teens and adults.

In fact, this group is around 25 times more likely than the overall population to develop schizophrenia, presenting a chance to study the genetic origin of the disorder and create novel therapeutics to treat it.

In a previous study, CHOP researchers looked at stem cell-derived neurons and discovered that individuals with 22q and schizophrenia exhibited mitochondrial dysfunction when compared to healthy controls. That research, however, did not take into consideration 22q individuals who did not develop schizophrenia.

Schizophrenia is a very complex mental health disorder, and it can be particularly debilitating for patients with 22q when coupled with a myriad of other health challenges. In this most recent study, it was important to define the role mitochondria play in determining which patients with 22q – particularly teenagers – are likely to develop schizophrenia.”

Stewart A. Anderson, MD, Study Senior Author and Director of Research, Department of Child and Adolescent Psychiatry and Behavioral Services

Anderson is also the associate director of CHOP and Penn’s Lifespan Brain Institute.

Using different lines of stem cells than in the previous study, the researchers evaluated mitochondrial activity and gene expression in adults with 22q and a control group, where the 22q group included neurons from people with and without schizophrenia.

The researchers found that mitochondrial function was affected in patients with 22q and a schizophrenia diagnosis and lower amounts of ATP, a primary energy source for cells that is mostly generated by mitochondria.

ATP levels, on the other hand, were not lowered in 22q individuals who were not diagnosed with schizophrenia. Indeed, when compared to both the 22q and schizophrenia groups and the control group, the expression of numerous genes encoding for oxidative phosphorylation, a mechanism that helps create ATP, was elevated.

These results imply that enhanced mitochondrial biogenesis is linked to a lack of schizophrenia in 22q.

Bioenergetics and mitochondria have historically not been thought to play a significant role in autism spectrum disorders and schizophrenia, but our findings from this study coupled with previous findings show that mitochondrial dysfunction may play an important role in these neuropsychiatric disorders.”

Douglas C. Wallace, PhD, Study Co-Author and Director, Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia

“Recognizing the role of mitochondrial dysfunction in neuropsychiatric disorders may lead to the development of better diagnostic tools as well as targeted treatments for patients with 22q-associated schizophrenia,” added Wallace.

Patients with 22q present with a wide variety of symptoms, and while our team helps families navigate these challenges across many different medical specialties, the sheer number of associated features can significantly impact both the patients and their families’ lives – with behavioral health being the most complex and difficult to manage.”

Donna M. McDonald-McGinn, MS, CGC, Study Co-Author and Director, 22q and You Center

McDonald-McGinn is also the Associate Director of the CHOP Clinical Genetics Center.

“The more we know about how each individual is affected at a deeper genomic level, the more resources we can provide to families, while pivoting future research efforts towards finding new ways to help our patients, as well as those in the general population with schizophrenia but without 22q,” concluded McDonald-McGinn.