Depression: sygdom eller symptom?

In this post we will discuss whether depression is a disease and therefore causes symptoms and how to avoid it. Or if it is a symptom and therefore a consequence of something.

Depression as a chemical imbalance

The idea that depression and other mental health problems are caused by an imbalance of chemicals in the brain (especially serotonin and norepinephrine) is deeply ingrained in our collective psyche. It even seems almost sacrilege to question it.

11% of Americans over the age of 12 take antidepressants

Of course Big Pharma has played a role in perpetuating this idea. Antidepressant drugs, based on the chemical imbalance theory, represent a ten billion dollar market in the US alone. According to the US Centers for Disease Control and Prevention, 11% of Americans over the age of 12 years take antidepressants. And these are the second most prescribed drugs (after drugs to lower cholesterol, which deserve a separate post).

Doctors prescribed a staggering 254 million antidepressants in 2010 

However, the neurotransmitter deficiency theory, while so popular, is riddled with inconsistencies:

Reduced levels of norepinephrine, serotonin, and dopamine do not produce depression in humans. Yes it seems to do it in animals.
Although some patients with depression have low levels of serotonin and norepinephrine, most do not. Several studies indicate that only 25% of depressed patients have low levels of these neurotransmitters.
Some depressed patients have abnormally high levels of serotonin and norepinephrine. Other patients with no history of depression have low levels of them. 
These data lead us to ask ourselves several questions. Could it be that depression isn’t caused by a “chemical imbalance” after all? And, going even further: what if depression itself was not an illness, but a symptom of an underlying problem?

Pills for depression. Depression as a symptom

That’s exactly what some recent research on depression is showing us. A new theory called the Immunocytokine Model of Depression holds that depression is not a disease in itself. This is a “multifaceted sign of chronic activation of the immune system.” 

To put it plainly: depression can be a symptom of chronic inflammation.

A large body of research now suggests that depression is associated with low-grade chronic inflammation or silent inflammation. It is also accompanied by an increase in oxidative stress.

In an excellent review article by Berk and other researchers, the authors present several lines of evidence supporting the connection between depression and inflammation: 

According to a recent meta-analysis, depression is often present in acute inflammatory illnesses. 
High levels of inflammation increase the risk of developing depression.
The administration of endotoxins that cause inflammation in healthy people triggers classic depressive symptoms.
A quarter of patients taking interferon, a drug used to treat hepatitis C, have significant inflammation, developing further depression. 

Remission of clinical depression is often associated with normalization of inflammatory markers. 
Our lifestyle habits are full of factors that cause inflammation. In turn, causing depression

During an inflammatory reaction, chemicals called “cytokines” are produced. These substances include, among others, tumor necrosis factor (TNF) α, interleukin (IL)-1, interferon (IFN) ɣ, and interleukin (IL)-10, among others. As early as the 1980s, it was discovered that inflammatory cytokines produce a wide variety of psychiatric and neurological symptoms that perfectly reflect the defining characteristics of depression. 

The research on this topic is solid, and the connection between depression and inflammation is fairly well established. The point is that our lifestyles are full of factors that cause inflammation. In turn, the cause of the disease at hand. The advantage is that if we address these factors and reduce inflammation, chronic inflammatory diseases can be prevented and even reversed. Which have become a kind of accessory to industrial civilization.

It is nice to present all this data. They support our idea that doing sports and eating consistently is not only good health. You are also happier.

I guess by now we’re all asking ourselves the same question: 

what causes inflammation?

Diet

Pineapples, red and yellow peppers, pears and cauliflowers
There are several problems with the modern diet. It is rich in foods that cause inflammation. For example refined flour, excess sugar, oxidized (rancid) fats, trans fats and a wide range of chemicals and preservatives. And it’s low in foods that reduce inflammation, such as long-chain omega-3 fats, fermented foods, and fermentable fiber. Numerous studies have associated the Western diet with major depressive disorder. 

If you want to feel good, eat foods that your body recognizes. They can be fruit, vegetables and tubers: mushrooms, algae, fish, meat, eggs, shellfish.

Obesity

One of the most damaging consequences of the modern diet has been the dramatic rise in obesity. Obesity is an inflammatory state. Studies have shown higher levels of inflammatory cytokines in obese people. Also, that weight loss is associated with a decrease in these cytokines.  Obesity is closely related to depression. And, although that relationship is probably multifactorial and complex, inflammation seems to play an important role in it. 

Gut health

Mismatches in the gut microbiome and leaky gut have been shown to be contributing factors to inflammation. So they correlate with depression. For example, a leaky gut allows lipopolysaccharide (LPS) endotoxins to escape the intestine and enter the bloodstream. There they cause the release of inflammatory cytokines such as TNF-α, IL-1 and COX-2.  In addition, numerous studies have linked unfavorable changes to the bacteria that inhabit our intestines with major depressive disorder. 

Psychosocial stress stimulates the network of pro-inflammatory cytokines, related to depressive symptoms

Stress

Stress can be one of the most obvious causes of depression. But the link between stress and inflammation is less well understood. Research has shown that psychosocial stress stimulates the network of pro-inflammatory cytokines, including increases in TNF-α and IL-1.  These increases in inflammatory cytokines are, in turn, closely related to depressive symptoms, as described above.

Physical activity

There is a tremendous amount of evidence that exercise is an effective treatment for depression. In many cases it is as effective or more than antidepressant drugs. It has also been shown to be helpful in preventing depression in healthy people with no pre-existing symptoms.

Interestingly, as we will explain in another post in a couple of weeks, while exercise initially produces the same inflammatory cytokines that are associated with depression, this response is quickly followed by the induction of potent anti-inflammatory substances.  This is known as the hormetic effect. This is where an initial stressor triggers a compensatory response in the body that has positive long-term consequences.

sleep deprivation

Chronic sleep loss has been shown to increase markers of inflammation, even in otherwise healthy people.  And although temporary sleep deprivation has been used therapeutically to improve depression, chronic sleep loss is a well-known contributing factor in the development of depression. 

Chronic infection

Chronic infections cause inflammation. Thus, it is not surprising to see that depression is associated with infections with Toxoplasma gondii, West Nile virus, Clostridium difficile, and other pathogens.

The researchers found that people with depression were more likely to have tooth loss.

Tooth decay and periodontal disease are another source of chronic inflammation, and thus a possible cause of depression. In a large study of more than 80,000 adults, researchers found that people with depression were more likely to have tooth loss. Even after controlling for various demographic and health factors. 

Vitamin D deficiency

Low levels of vitamin D are common in the Western population. There is growing evidence linking deficiency of this vitamin with depression. Vitamin D modulates the immune response during an infection, including the reduction of inflammatory markers associated with depression, such as TNF-α and IL-1. 

Vitamin D supplementation to normalize serum 25D levels has been shown to reduce inflammatory markers in some, but not all, cases.

Final reflection

Understanding the physical roots of depression can have a profound effect on people who suffer from it. Although the stigma surrounding depression has lessened in recent years, many who are depressed still carry the burden of thinking that something is wrong with them, and the depression they experience is “their fault.” When my patients with depression learn that their symptoms have an underlying physiological cause, they often feel a tremendous sense of relief and empowerment.

I do not mean to suggest that emotional and psychological factors do not play a role in depression. In many cases they do. The question is what kind of bodily state an individual must have so that, faced with a negative thought or life situation, they develop depression while another does not. A state of silent inflammation could bring us closer to the answer.

So, after all, to be happy we must also eat well, move, let the sun shine on us, sleep… The rest will come by itself.