Scientists link insulin resistance to increased risk of developing major depressive disorder

Stanford Medicine scientists have linked insulin resistance to an increased risk of developing a major depressive disorder.

"If you're insulin-resistant, your risk of developing major depressive disorder is double that of someone who's not insulin-resistant, even if you've never experienced depression before," said Natalie Rasgon, MD, PhD, professor of psychiatry and behavioral sciences.

Upward of 1 in 5 Americans experiences major depressive disorder sometime during their lives. Symptoms include unremitting sadness, despair, sluggishness, sleep disturbances, and loss of appetite. Some factors contributing to this deeply debilitating disease — childhood traumas, loss of a loved one, or the stresses of the COVID-19 pandemic, for example — are things we can't prevent. But insulin resistance is preventable: It can be reduced or eliminated by diet, exercise, and, if need be, drugs.

The researchers' findings are described in a study published online on Sept. 22 in the American Journal of Psychiatry. Rasgon shares senior authorship of the study with Brenda Penninx, MD, PhD, professor of psychiatric epidemiology at the University of Amsterdam Medical Center. The study's lead author is Kathleen Watson, PhD, a postdoctoral scholar in Rasgon's group.

A common but silent condition

Studies have confirmed that at least 1 in 3 of us is walking around with insulin resistance — often without knowing it. The condition does not arise from a deficiency in the pancreas's ability to secrete insulin into the bloodstream, as occurs in Type 1 diabetes, but because of the decreased ability of cells throughout the body to heed this hormone's command.

Insulin's job is to tell our cells it's time for them to process the glucose that's flooding our blood due to our dietary intake of it, its manufacture in our liver or both. Every cell in the body uses glucose as fuel, and each of those cells has receptors on its surface that, on binding to insulin, signals the cell to ingest the precious energy source.

But an increasing proportion of the world's population is insulin-resistant: For various reasons — including excessive caloric intake, lack of exercise, stress and not getting enough sleep — their insulin receptors fail to bind to insulin properly. Eventually, their blood sugar levels become chronically high. Once those levels stay above a certain threshold, the diagnosis is Type 2 diabetes, a treatable but incurable condition that can lead to cardiovascular and cerebrovascular disorders, neuropathy, kidney disease, limb amputations, and other detrimental health outcomes.

Associations between insulin resistance and several mental disorders have already been established. For example, it's been shown that about 40% of patients suffering from mood disorders are insulin-resistant, Rasgon said.

But these assessments have been based on cross-sectional studies — snapshots of populations at a single point in time. The question of whether one event was the cause or the result of the other — or whether both were results of some other causal factor — are best resolved by longitudinal studies, which typically track people over years or even decades and can determine which event came first.