Insulin Resistance and Depression

Major depressive disorder is the leading cause of disability worldwide. Yet, there remain significant challenges in predicting new cases of major depression and devising strategies to prevent the disorder. An essential first step in this process is identifying risk factors for the incidence of major depressive disorder.

There is accumulating biological evidence linking insulin resistance with depressive disorders. Scientists have observed an increased risk of depression-like behaviors, neuroinflammation, dysregulated mitochondrial function, and decreased neurogenesis in animal models of insulin resistance. In addition, studies show that treatment for insulin resistance in animals can reverse depression-like behavior.

Insulin resistance can lead to the development of type 2 diabetes, which, without proper management, can lead to severe health problems. Major depressive disorder is a common and severe mental health problem. Its prominence means that researchers are striving to identify factors that put people at risk of developing depression.

A new study by researchers at Stanford University School of Medicine, CA, found that participants with insulin resistance had a higher risk of developing depression than those who did not. The findings appear in The American Journal of Psychiatry.

Insulin Resistance 

As the Centers for Disease Control and Prevention (CDC) notes, the chronic condition of diabetes centers around the hormone insulin, which the pancreas produces. When the body releases insulin, this hormone allows the body’s cells to absorb sugar from the food the person eats.

Without enough insulin, the sugar from food builds up in the bloodstream, depleting the body’s energy stores. Excessively high levels of blood sugar can lead to serious long-term health complications. Currently, 34.2 million people have diabetes in the United States, the seventh leading cause of death.

Major Depressive Disorder

Major depressive disorder, which people commonly call depression, is a highly prevalent mental health condition. The CDC estimates that 1 in 6 adults will experience depression at some point in their life.

Due to the significance of depression, researchers continue to look into risk factors that can help detect and treat the condition at an earlier stage.

What Link did the Research Found?

The study collected data from patients who were part of the Netherlands Study of Depression and Anxiety. The researchers followed the study participants over nine years. The study included 601 participants that had no previous history of clinical depression or anxiety. Researchers screened the participants for depression and other psychiatric disorders, took lab samples, and checked their physical measurements at their initial evaluation and after two years. 

Then participants underwent psychiatric evaluations 4, 6, and 9 years after the initial assessment. The researchers accounted for several covariates, including the participants’ age, sex, education level, level of physical activity, smoking status, and alcohol use. Their primary analysis found that all three indicators of insulin resistance were associated with an increased risk of depression. These factors are: 

  1. The ratio of triglycerides to high-density lipoprotein cholesterol. 
  2. Blood sugar level.
  3. Waist circumference. 

They further examined the subgroup of people who did not show indicators of insulin resistance when the study started. They found that those who developed prediabetes during the first two years of the study were more than twice as likely to be experiencing major depression at the nine-year follow-up than those who had normal plasma glucose levels at the two-year point. 

The researchers’ work suggests that specific treatments that decrease insulin resistance can aid in the treatment of major depression in some patients. Future studies are needed to see if reversing insulin resistance can reduce the risk of developing a major depressive disorder. 


Kathleen T. Watson, et al. Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study. Am J Psychiatry 2021; 00:1–7; doi: 10.1176/appi.ajp.2021.20101479