Insulin resistance increases risk of major depressive disorder

Stanford Medicine scientists have linked insulin resistance to an increased risk of developing major depressive disorder. The researchers' findings are described in a study, ‘Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study’, published in the American Journal of Psychiatry.

"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 co-author of the study, Dr Natalie Rasgon, professor of psychiatry and behavioral sciences.


Upward of one in five Americans experience major depressive disorder sometime during their lives. Symptoms include unremitting sadness, despair, sluggishness, sleep disturbances and loss of appetite. Rasgon explained that associations between insulin resistance and several mental disorders have already been established - about 40% of patients suffering from mood disorders are insulin-resistant. However, these assessments have been based on cross-sectional studies, snapshots of populations at a single point in time.


As a part of a multi-institutional collaboration within a research network Rasgon established in 2015, a team of researchers obtained data from an ongoing longitudinal study monitoring more than 3,000 participants in scrupulous detail to learn about the causes and consequences of depression: the Netherlands Study of Depression and Anxiety.


"The Dutch study, with its meticulous monitoring of a large subject population for nine years and still climbing, presented a great opportunity for us," said the study's lead author, Dr Kathleen Watson.


The Stanford team analysed data from 601 men and women who served as control subjects for the Netherlands study. At the time of their enrolment, 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.


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: They discovered that a moderate increase in insulin resistance, as measured by the triglyceride-to-HDL ratio, was linked to an 89% increase in the rate of new cases of major depressive disorder. Similarly, every 5cm increase in abdominal fat was related to an 11% higher rate of depression, and an increase in fasting plasma glucose of 18 milligrams per deciliter of blood was associated with a 37% higher rate of depression.


"Some subjects were already insulin-resistant at the study's start, there was no way to know when they'd first become insulin-resistant," added Watson. "We wanted to more carefully determine how soon the connection kicks in."


So, 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. Therefore, the authors noted that insulin resistance is a strong risk factor for serious problems, including not only Type 2 diabetes but depression.


"It's time for providers to consider the metabolic status of those suffering from mood disorders and vice versa, by assessing mood in patients with metabolic diseases such as obesity and hypertension," added Rasgon. "To prevent depression, physicians should be checking their patients' insulin sensitivity. These tests are readily available in labs around the world, and they're not expensive. In the end, we can mitigate the development of lifelong debilitating diseases."


Further information

To access this paper, please click here