Insulin resistance doubles risk of major depressive disorder, Stanford researchers find

Stanford Medicine scientists have linked insulin resistance to an increased risk of developing major depressive disorder in a new study published in the American Journal of Psychiatry.

The researchers obtained data from the Netherlands Study of Depression and Anxiety, an ongoing longitudinal study monitoring more than 3,000 participants to learn about the causes and consequences of depression. The team analyzed data from 601 men and women who served as control subjects for the Netherlands study. At the time of their enrollment, they’d never been troubled by depression or anxiety. Their average age was 41 years.      

The team measured three proxies of insulin resistance: fasting blood glucose levels, waist circumference, and the ratio of circulating triglyceride levels to those of circulating high-density lipoprotein (HDL) or “good” cholesterol. They probed the data to see if the subjects found to be insulin-resistant had a heightened nine-year risk of developing major depressive disorder.

By all three measures, the answer was yes. The researchers discovered that a moderate increase in insulin resistance, as measured by the triglyceride-to-HDL ratio, was linked to an 89 percent increase in the rate of new cases of major depressive disorder. Similarly, every five-centimeter increase in abdominal fat was related to an 11 percent higher rate of depression, and an increase in fasting plasma glucose of 18 milligrams per deciliter of blood was associated with a 37 percent higher rate of depression.

The researchers restricted the next phase of their analysis to the roughly 400 subjects who, in addition to never having experienced major depression, also showed no sign of insulin resistance at the study’s onset. Within the first two years of the study, nearly 100 of these participants became insulin resistant. The researchers compared this group’s likelihood of developing major depressive disorder in the next seven years with that of the participants who hadn’t yet become insulin-resistant at the two-year point.      

While the number of participants was too small to establish statistical significance for waist circumference and the triglyceride-to-HDL ratio, the results for fasting glucose were not only statistically significant, but clinically meaningful. Those developing prediabetes within the first two years of the study had 2.66 times the risk for major depression by the nine-year follow-up milepost, compared with those who had normal fasting-glucose test results at the two-year point, the researchers said.

Insulin resistance is a strong risk factor for serious problems, including not only type 2 diabetes but depression, the researchers said.