Award Winner Describes Efforts to Improve Cognition in People With Bipolar Disorder

McIntyre noted that about 50% of people with bipolar disorder have comorbid diabetes or pre-diabetes.

“Insulin has a neuroprotective role in the brain,” he said, adding that insulin resistance has been linked with accumulation of Alzheimer’s-related amyloid proteins. In addition, insulin can also inhibit the enzyme monoamine oxidase—the same enzyme targeted by antidepressants known as monoamine oxidase inhibitors (MAOIs).

For a long time, measuring insulin signaling in the brain was challenging. In 2021, McIntyre’s colleague at the University of Toronto, Rodrigo Mansur, M.D., led a study that managed to isolate brain-derived vesicles from the blood of patients with bipolar disorder. The researchers found evidence to suggest that individuals with cognitive problems had insulin resistance that spread to the brain.

“So how do we slow this process down?” McIntyre asked. Fortunately, the same approaches that target diabetes and insulin resistance in the rest of the body may improve psychiatric symptoms, he said. A 2012 study by McIntyre suggested that intranasal insulin therapy was associated with executive function improvements in people with bipolar disorder, for example. Another study published in 2022 found metformin could lead some people with bipolar disorder to convert from an insulin-resistant to insulin-sensitive state, and those who converted showed significant improvements in depressive symptoms after six months.

McIntyre noted that he’s keeping close watch on the new weight loss drugs called GLP-1 agonists (Ozempic and related medications).

“There is evidence that GLP-1 agonists have direct effects on the brain, including an ability to restore dopamine imbalance.”

“What if these agents are psychiatric drugs that are masquerading as weight loss drugs?” McIntyre said.

He noted that his group in Toronto has just launched a clinical trial testing Ozempic as an adjunct medication for the treatment of cognitive problems in people with major depression. And he’s not alone; he said that organizations in both the private and public sectors are looking at repurposing these diabetes medications.

“When I sat with my first bipolar patient, no one was talking about psychiatry and metabolism, but the field has now taken off,” McIntyre said. “I really think this will soon open up a new section on the drop-down menu of therapeutics for people living with depression or bipolar disorder.” ■