If Insulin resistant, Risk of Depressive Disorder Increases 

A group of scientists from the Stanford Medicine have linked insulin resistance to an increased risk of developing major depressive disorder. The findings are published online in the American Journal of Psychiatry.

“If you are insulin-resistant, your risk of developing major depressive disorder is double that of someone who is not insulin-resistant, even if you have never experienced depression before,” said Natalie Rasgon, professor of psychiatry and behavioural sciences.

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.


The authors say that at least one in three people are walking around with insulin resistance, probably without knowing it. They say that the condition does not arise from a deficiency in the pancreas’s ability to secrete insulin into the bloodstream as in Type 1 diabetes. This happens because of the decreased ability of cells throughout the body to heed this hormone’s command.

Insulin tells the cells that it is time for them to process the glucose that is flooding the blood due to dietary intake, 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.

However, an increasing proportion of the world’s population is insulin-resistant. They say that this could be because of excessive caloric intake, lack of exercise, stress and not getting enough sleep.  As such, the insulin receptors fail to bind to insulin properly. Eventually, their blood-sugar levels become chronically high.

The researchers got 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. Rasgon is the Stanford principal investigator, and Penninx is the overall principal investigator.


The Stanford team analyzed data from 601 men and women who served as control subjects for the Netherlands study. At the time of their enrollment, they had never been troubled by depression or anxiety. Their average age was 41 years. The team measured three proxies of insulin’s resistance: fasting blood glucose levels, waist circumference, and ratio of circulating triglyceride levels to those of circulating high-density lipoprotein – or HDL. They looked into various data to see if the subjects found to be insulin-resistant had a heightened nine-year risk of developing major depressive disorder. They found that this happened. They found that a moderate increase in insulin resistance was linked to an 89 per cent increase in the rate of new cases of major depressive disorder. Similarly, every 5-centimeter increase in abdominal fat also led to 11 per cent higher rate of depression.

An increase in fasting plasma glucose of 18 milligrams per deciliter of blood was related to a 37 per cent higher rate of depression in the next phase, the researchers analysied about 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 then compared this group’s likelihood of developing major depressive disorder in the next seven years with that of the participants who had not yet become insulin-resistant at the two-year point.

Rasgon pointed out that it was time 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. Physicians should check their patients’ insulin sensitivity to prevent depression



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