Insulin Is an Antidepressant: A Conversation With Roger McIntyre, MD, FRCPC

TALKING WITH TITANS OF PSYCHOPHARMACOLOGY

At the 2025 American Psychiatric Association (APA) Annual Meeting, Psychiatric Times' Editor in Chief, John J. Miller, MD, sat down with leaders in psychopharmacology to discuss the topics they find most important.

Roger S. McIntyre, MD, FRCPC, has spent several decades dedicated to understanding the impact of insulin and metabolism on the brain.¹

"A lightbulb moment for me happened while seeing patients. Our patients with depression or bipolar disorder are more likely to have conditions like obesity, diabetes, and metabolic syndrome. That is very well-known. But what was especially curious to me is when someone had one of these or more related problems, they were more likely to say, 'My mind is foggy, I can't think, I can't focus,'" said McIntyre.

The first patient in the world to receive insulin in type II diabetes was in Toronto.² McIntyre sought to understand the role that metabolism and metabolic peptides play in normal and abnormal cognitive and reward functioning.

"What I discovered was insulin plays a critical role in mood regulation and cognition. And I thought, why don't we study this as a treatment for depression or bipolar disorder? That ignited 25-30 years of curiosity in pursuit of this question," shared McIntyre.

McIntyre believes we can get to transformation 2.0 in psychiatry therapeutically if we better understand the underlying mechanisms of the brain that are leading to these disease states, and more specifically domains like reward and cognition. He also shared that interventions like diet, sleep, and chronotherapeutics that can directly or indirectly affect insulin or related systems, are worth pursuing.

"I would love to tell a patient, 'This treatment will stop your illness in its tracks and even reverse it,'" said McIntyre.

McIntyre also explained the effect of insulin in the brain for patients with diabetes. For example, as type II diabetes progresses, and people have decreased insulin production over time, it leads to lessened availability of insulin to the brain for trophic and plasticity support. In the early days of type II diabetes, the brain is exposed to hyperinsulinemia. That results in a deposition of a variety of molecules that trigger inflammatory cascades. Over the longer term, there is a relative deficiency or pulling back of trophic support.

"Insulin the key role in plasticity and trophic support at the cellular level, which is the component that is regulating some of the circuit connectivity, like forming synapses, synaptic strength, synaptic connectivity," said McIntyre. "In diabetics, you see an impairment in brain networking circuit synchronization."

McIntyre is excited to see psychiatry explore other avenues besides serotonin. "The story on metabolism not only feels right, but it is having a predictable, reproducible effect on aspects of psychopathology that we have struggled with, that being cognitive impairment, cognitive loss, and reward-type disturbances," concluded McIntyre.

Dr McIntyre is a professor of Psychiatry and Pharmacology at the University of Toronto and head of the Mood Disorders Psychopharmacology Unit at the University Health Network, Toronto, Canada.

Dr Miller is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief, Psychiatric Times; Voluntary Consulting Psychiatrist at Seacoast Mental Health Center, Exeter/Portsmouth, NH; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

References

1. McIntyre RS. Surrogate markers of insulin resistance in predicting major depressive disorder: metabolism metastasizes to the brain. Am J Psychiatry. 2021;178(10):885-887.

2. The history of a wonderful thing we call insulin. American Diabetes Association. Updated July 1, 2019. Accessed May 22, 2025. https://diabetes.org/blog/history-wonderful-thing-we-call-insulin