Insulin Resistance and Depression

Depression is remarkably common. Close to one in five Americans are diagnosed with depressive illness at some point in their lives. Insulin resistance, a stepping-stone on the path to type 2 diabetes (not to mention cardiovascular disease and probably Alzheimer’s), is even more common: About one in three otherwise healthy Americans – and an even greater share of people with depression – are insulin-resistant. Especially prevalent among overweight people, insulin resistance also occurs more often than one might expect even among thinner folks, a lot of whom don’t have the faintest idea that’s the case.

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What is Insulin?

Insulin, released by the pancreas in response to your food intake, alerts cells throughout the body on the presence of glucose in the blood, the body’s primary energy source. Insulin-resistant people’s cells fail to take up glucose adequately, leaving high residual blood levels of the sugar to wreak havoc on the body’s tissues. Because the brain is a glucose glutton – it soaks up about 20 percent of all glucose consumption in a healthy, active person – it’s easy to imagine that lousy glucose uptake in the brain would have all kinds of deleterious effects, including effects on mood. Uncontrolled insulin resistance can harm your nerves and vital organs. It can result in depression.

Insulin Resistance

Insulin resistance occurs when insulin does not bind properly to insulin receptors, or insulin receptors fail to properly transmit the message to the cells that it is time to eat.

The muscle, fat and liver cells of an insulin-resistant person don't respond to insulin as well as they should so their pancreas makes more and more and eventually can't keep up with the demand. This leads to excess glucose in the bloodstream, and prediabetes.

Many people with insulin resistance have both high insulin and high glucose levels in their blood at the same time.

The body actually responds in the same way as it would during starvation. It will break its stored forms of glycogen into glucose and trigger further secretion of insulin into the bloodstream. It will also trigger hunger. This quickly leads to high glucose levels, low energy and mood swings. More severe cases of insulin resistance lead to type 2 diabetes. In type 2 diabetes the glucose levels are dangerously high, and the body adjusts by excreting glucose in the urine.

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Depression before Onset

As reported in the previous studies, insulin resistance is significantly correlated with depression. Depression typically sets in prior to the onset of diabetes, making the cause of the depression harder to identify. The mechanism of action is poorly understood. It is possible that insulin resistance may trigger the production of counter-regulatory hormones that play a role in depression. Cortisol is a stress hormone that helps to provide energy to the muscles. High levels of cortisol are significantly linked to depression. Another suspect hormone is glucagon-like-peptide-1, or GLP-1. As GLP-1 inhibits food intake, the body may produce it in response to insulin resistance. GLP-1 is thought to trigger anxiety and depression.  

Treating Depression as a Nutritional Disorder

Sydney-based clinical nutritionist Jurriaan Plesman suggests that depression is a nutritional disorder. The thrust behind this claim is that cells need energy to produce neurotransmitters, such as the neurotransmitter serotonin, which appears to be linked to depression. If the body is resistant to insulin, however, then the body's cells do not get enough energy. The body seeks to stay alive. So, it will cut energy where it can. As a result, the levels of neurotransmitters, including serotonin, are reduced, and this causes depression.

Plesman suggests that the best way to treat depression is to follow a hypoglycemic diet. This kind of diet provides essential nutrients and cuts sugar and processed carbohydrates but encourages the consumption of a protein-complex carbohydrate snack every three hours. The aim is to stabilize glucose levels and thereby stabilize the levels of neurotransmitters and stress hormones. The diet is not a quick fix. Correcting the abnormal levels of hormones and neurotransmitters may take several months or, in severe cases, years.

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Recent Studies

A new small study is adding evidence to the theory that insulin resistance may play a leading role in some cases of depression. Findings from the study were published online Oct. 12 in Psychiatry Research.

The study included 37 adults – 29 women and eight men – recruited at Stanford University in California. The study volunteers were between 21 and 75 years old and their weight ranged from underweight to severely obese. None had diabetes, but some were insulin-resistant or had prediabetes. All of the study volunteers had depression for longer than a year. Study volunteers received 12 weeks of treatment with pioglitazone or an inactive placebo. Patients were allowed to stay on their current antidepressant treatment as well.

Participants who were insulin-sensitive had improvements in their depression whether they were taking the drug or a placebo. But those who were insulin-resistant only saw improvement in their depression symptoms if they were taking the insulin-sensitizing drug. People who were insulin-resistant who took the placebo didn't see improvement. The more insulin-resistant someone was, the better the drug worked on their depression, the researchers noted.

These findings "add to the neurobiological explanation of what's going on when people are depressed, and it should help de-stigmatize depression. It's a disease of the brain," lead author Natalie Rasgon, MD, PhD, a professor of psychiatry and behavioral sciences at the Stanford University School of Medicine, said in interview.

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