Brain energy key to new mental health treatments

Posted: 30th March 2021

There have been no new effective treatments for people with bipolar disorder since Australian psychiatrist John Cade first used lithium to treat patients in the 1940s. To this day, the scientific community still doesn’t know exactly how, or why, lithium works. “It is now becoming clear that the manic and depressive phases of bipolar disorder are triggered by imbalances in brain energy metabolism,” says Dr John Scott, leader of the Neurometabolism Team in SVI’s Protein Chemistry & Metabolism Unit.

“My work focuses on an enzyme called Ca2+-dependent protein kinase kinase-2, or more simply, CaMKK2. This is a key regulator of energy metabolism. Our team’s studies have shown that mutations that stop the normal function or availability of CaMKK2 are associated with bipolar disorder, and there is other evidence to suggest that CaMKK2 would be a good target for treatment.”

By investigating mice as a model for how these energy regulators work in humans, the Neuro-metabolism Team is uncovering more about the molecular cause of bipolar disorder. They have also generated small molecules – potential drugs – that affect CaMKK2 function.

John is hopeful that treatments that may flow from this world-leading research will reflect the collective effort of scientists and clinicians towards deeper understanding of the complex and fundamental biological mechanisms deep inside our brains.

“It’s been a long time coming, but I’m optimistic that we are getting closer to creating more effective treatments for bipolar and other mental health disorders.”

John’s work is supported by an NHMRC Ideas Grant and an ARC Discovery Grant.