Is Some Depression Actually Insulin Resistance?

This post summarizes some of the latest science about a condition called insulin resistance and how it is a largely unrecognized cause of depression symptoms.

Remarkably, as of 2022, most people have still never heard of insulin resistance. This is true even though it is the single most common chronic health condition in the U.S. and a major contributor to six of the top eight causes of death in 2021 (heart disease, cancer, COVID, stroke, Alzheimer’s disease, and diabetes). How common can insulin resistance be if you’ve never heard of it? Extremely common; an estimated 88 percent of U.S. adults in 2018 had this condition (1).

Briefly stated, insulin resistance is a process in which cells become less responsive to a hormone called insulin. Because insulin receptors are found in every cell in the body—muscle, fat, organs, bone, skin—how well cells respond to insulin signals is critical to how we feel and function.

One of insulin’s main functions is to help the body control blood sugar levels by putting excess blood sugar into cells for storage. This process occurs every time you eat. Because insulin is so crucial to blood sugar regulation, even people who have heard of insulin or insulin resistance mostly think of it as a problem for diabetics.

Indeed, this is partly true. In people with diabetes, their cells have become so resistant to insulin that insulin can no longer keep their blood sugar levels in a healthy range. As a result, blood sugar levels run high, with catastrophic consequences if left unchecked.

Unfortunately, even when a person with diabetes receives treatment, this treatment doesn’t necessarily improve their underlying insulin resistance; a person can lower blood sugar levels while remaining insulin resistant, giving them a false sense of security about their health.

For example, although the science is not yet strong enough to make it an official diagnosis, many researchers now refer to Alzheimer’s disease, the progressive and fatal form of dementia associated with severe memory loss, as “Type 3 diabetes” in reference to the effects possibly being the result of long-term insulin resistance in the brain (2).

How does this happen? Among other effects still being investigated, insulin resistance results in a buildup of amyloid β plaques, causing inflammation and neurodegeneration, and disrupting neuron signaling.

The rapidly evolving science on insulin resistance and brain function now also suggests that effects could extend beyond dementia to include depression.

Depression is a condition defined by a heterogeneous collection of symptoms. Some of the classic symptoms of depression—such as sadness, guilt, suicidality, and poor concentration—are believed to result from dysfunction in a neurotransmitter called serotonin. Popular antidepressants such as Prozac work by improving serotonin function in the brain.

In contrast, other common symptoms of depression such as anhedonia (a lack of motivation or interest), fatigue, motor impairment, and loss of sex drive are more closely linked to dysfunction in other neurotransmitters such as dopamine and norepinephrine. This is another area where insulin resistance becomes especially relevant. 

In addition to the above-mentioned neurocognitive effects related to dementia, insulin resistance also impairs dopamine function and causes mitochondrial dysfunction in the brain (3).

As insulin resistance becomes chronic and more severe, it also becomes increasingly likely to manifest in the somatic symptoms we routinely associate with depression. However, because these symptoms are instead the result of insulin resistance, neither psychotherapy nor conventional antidepressants are likely to help.

Reversing insulin resistance can help (also called improving insulin sensitivity). There is good news: Insulin resistance is highly reversible with lifestyle changes. Even without weight loss, for example, regular exercise improves insulin resistance.

Nutrition is even more powerful. Reducing your intake of sugar, fructose, and ultra-processed foods, for example, can improve insulin sensitivity within days to weeks (again, even without weight loss, although weight loss also improves insulin resistance).

For this reason, intermittent fasting, where you consume calories in one to two meals a day or only during a limited window of hours during the day, improves insulin resistance even if the total calorie intake and food choices are the same. Lastly, one of the reasons that sleep improves depression is probably because the many benefits of sleep include reduced insulin resistance (4).

Summary

Insulin resistance is the most common and least appreciated cause of our modern epidemic of chronic diseases.

Although we once thought the harms of insulin resistance were limited to metabolic diseases such as obesity and diabetes, we now know that these effects extend to cognitive function and depression as well. Thankfully, these effects are not only reversible but reversible through lifestyle changes alone for the person seeking to improve their physical and mental health.