An article by Janssen Research & Development, LLC, published in the May 2012 edition of Nature Reviews/Neuroscience reviews the increasing evidence that impaired mitochondrial function may have a major impact on mood and psychotic disorders.
The review includes a discussion of recent data from a large range of human and animal studies that strongly support the hypothesis that impaired mitochondrial function may disrupt neural plasticity pathways and decrease cellular resilience, which in turn, potentially encourages the development or progression of mood disorders, like major depression and bipolar disorder (BPD), as well as other psychiatric disorders with more limited available evidence, such as schizophrenia and autism.
The research discussed in the article underlines the high prevalence of psychiatric illness in many diseases that have a mitochondrial dysfunction or genetic mitochondrial defects. It also includes those studies that indicate that ‘healthy’ mitochondrial function can potentially be a key regulator of synaptic strength and cellular resilience in neuronal circuits that regulate complex, high-order brain functions, such as affect, cognition, behavior and perception.
Leading researcher, Husseini K. Manji, M.D., Global Therapeutic Area Head for Neuroscience at Janssen Research & Development, LLC explained:
“Unlocking the mysteries of brain function is fundamental to addressing the health and wellness of people who suffer from disorders like depression, bipolar disorder, and autism. In elucidating the role of mitochondrial function in the development and progression of these diseases, we are uncovering potential new avenues for their treatment. Our goal is to advance additional research and the development of new and novel therapeutics for these complex disorders.”
The authors stress that more research into mitochondrial dysfunction is necessary in order to help the development of such novel therapies to move forward, and they also state that new strategies in the development of truly novel treatments for highly disabling psychiatric illnesses are needed. They specifically call for the testing of compounds with improved central nervous system (CNS) penetration, as well as those other than simple antioxidants.
Given that mitochondria have a broad and fundamental impact on cellular processes, it may be particularly challenging to develop novel therapeutics that particularly target mitochondria because of their potential CNS-specific effects. The authors therefore recommend a new and potentially more efficient approach to drug development; i.e. an approach in which the smallest common denominator becomes the target of the therapy with later efforts being aimed at up-scaling therapies to obtain benefits for a more broad range of diseases that share underlying origins.
The most likely targets for a successful therapy would be disorders for which either the primary defect occurs in the mitochondria or those that have strong evidence that mitochondria have a major impact on disease pathology. A successful strategy like this would mean a possible, efficient and cost-effective benefit for a complete range of disorders that are linked to mitochondrial dysfunction.
Written By Petra Rattue