Depression is defined as a mood disorder that causes persistent feelings of sadness and loss of interest. The WHO (World Health Organization) predicts that depression will become the second leading cause of disability worldwide in the next five years.

The etiology of depression is the theory of an imbalance of chemicals, norepinephrine and serotonin, in the brain. This theory has deep roots such that the pharmaceutical industry has made a fortune selling antidepressants. Many of these antidepressants are serotonin reuptake inhibitors and their goal is to treat the bad chemistry in our body. Despite their wide usage, depression is still a big concern in everyday life. The reason behind this failure is possibly due to the true etiology of depression.

Scientists this time come out with a new theory – The Immune Cytokine Model of Depression, suggesting that depression may be caused by inflammation. This means that depression may not necessarily be a disease but a symptom instead.

There are many data in contrast with the theory of chemical imbalance, these include:

  • Depression in humans in not produced when the levels of norepinephrine, serotonin and dopamine are reduced.
  • Only 25% of patients with depression have low levels of serotonin and norepinephrine.
  • There can be abnormally high levels of serotonin and norepinephrine in some patients with depression.

On the other hand, there are many data supporting the theory of the immune cytokine model of depression, such as:

  • Many depressed patients have an activated immune system.
  • Depression is often present in acute illnesses.
  • Administration of endotoxin (lipopolysaccharide) and interleukin-1 (IL-1) to experimental animals manifests with symptoms resembling depression.
  • Patients that are treated with cytokines for other medical reasons show symptoms of depression.
  • Pro – inflammatory cytokines activate the HPAA (hypothalamo – pituitary – adrenocortical – axis) which is also activated in depression.
  • Cytokines activate the cerebral noradrenergic and serotonergic systems, which are involved in depressive illness.

Cytokines are immunomodulation agents that alter the immune response. They are important regulators of inflammation; they are released by cells and have a role in communication between cells. There are both pro-inflammatory and anti-inflmmatory cytokines. Cytokines include many molecules such as interleukins, lymphokines, tumor necrosis factor and the interferons.

A study led by researcher Dr. Argita Zalli about predicting the persistence of depressive symptoms in low-grade inflammation found that the dysregulation of the inflammatory response was associated with a more severe form of depression, and it was more likely to re-occur. This study assessed 656 individuals, they were evaluated for depression using the CES-D (Center for Epidemiologic Studies Depression Scale) at baseline and followed-up for five years. Also the markers of inflammation IL-6, ACT (alpha-1-antichymotrypsin) and CRP ( C-reactive protein) were assessed at baseline. The study found a positive association between baseline levels of IL-6 and CRP and persistence of depressive symptoms over five years.

This theory can bring a new era to the treatment of depression. If its etiology can be understood correctly it can have a profound effect on people who are suffering from depression. A lot of depressed patients have feelings of guilt for their symptoms because they think something is wrong with them. Knowing that depression can be a symptom and not a disease can have a tremendous sense of relief in their life.

These new data give an insight into the future of depression and an exciting filed to explore. Let’s hope that the underlying inflammation can be identified and treated promptly.


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