In Spain, more than 2.4 million people suffer from depression on a daily basis, which means that more than 5.2% of the Spanish population lives with a feeling of anguish and acute sadness that interferes with or makes it impossible to live their lives normally.

Despite the high incidence of this emotional disorder or condition, there is still great disagreement within the scientific community about the true cause of it. One of these theories is the theory of the discomfort of depression , which we explain throughout this article.

What is the malaise theory of depression?

Also known as the inflammatory theory of depression, this explanatory model of endogenous depression disorders created by the UK doctor and researcher Bruce G. Charlton in 2000, attempts to explain the origin of depression from a physical or organic point of view and not as a psychological reaction.

This theory begins with the idea that when our body is the victim of some type of infection, our own organism emits a response of inflammation by means of which a series of hemodynamic alterations, of the lymphatic levels and the liberation of a series of agents like cytokines, neuropeptide histamine, etc., are carried out with the purpose of restoring the health of our body.

In addition, along with inflammation appears a psychological phenomenon known as Illness behaviour . This type of psychological response is characterised by the fact that the person experiences a series of sensations of tiredness, drowsiness, anhedonia and cognitive alterations, all of which coincide with part of the clinical picture of major depression.

The origin of this disease behavior would be found in the effects that certain proteins, specifically cytokines, whose levels increase with the appearance of a virus or infection, cause in our brain.

This association between physical or organic response to inflammation and psychological response is what the theory of malaise suggests. According to it, endogenous depression is a pathological variety of disease behavior. For which the symptoms remain over time. Therefore, according to this theory, depression is caused by the effects of chronic, low-level organic inflation and chronic activation of the immune system.

Finally, Charlton himself proposes that the real effect of antidepressant drugs when it comes to alleviating the symptoms of the disease is found in the analgesic effect that most of them possess, so that by reducing organic inflammation, they also reduce the symptoms of depression.

On what evidence is this explanation based?

Although it’s initially hard to believe that a depression isn’t caused by an external factor that provokes this response, the theory of malaise is based on a body of empirical evidence that supports it.

1. Matching symptoms

As mentioned above, the symptoms of major depression are in many ways the same as those of illness behavior, which tends to occur when we have some form of physical illness.

In these cases symptoms such as fatigue, decreased physical energy or feelings of anguish and sadness appear with the aim of keeping our body at rest and recovering as soon as possible.

2. The effect of cytokines

One of the physiological responses that our body provokes when faced with the threat of a disease is the increase of cytokines . This protein causes inflammation with the intention of transmitting to our organism that it is in a state of alert or threat.

If we take into account that, usually, in disorders with depressive symptoms, cytokine levels are much higher than usual, we can hypothesize a kind of relationship between these two factors.

Furthermore, in the specific case of bipolar disorder, cytokine levels decrease during episodes of mania or remission of depressive symptoms , so this reinforces this association.

3. Action of antidepressants

Antidepressant drugs have an effect on cytokine levels, specifically by lowering them. This therefore reinforces the idea that the main cause of endogenous depression lies in the effects these proteins cause in the body.

4. The inflammatory response system and depression

Some studies have shown that the inoculation of substances or inflammatory agents in the laboratory causes a series of symptoms typical of clinical symptoms of depression and anxiety .

In addition, a clear relationship has been established between the activation of the body’s inflammatory response system and depression, as this is continuously activated during this disorder.

The inflammatory response system works through the activation of the hypothalamus-pituitary-adrenal axis, which affects the regulation of certain neurotransmitters such as serotonin and catecholamines, directly related to states of depression.

5. Antidepressant action of anti-inflammatory drugs

Finally, some research has found that the administration of anti-inflammatory medication in some cases of endogenous depression not only significantly improves the symptoms of depression, but also does so at a higher rate than some antidepressants.

What if there’s depression but no inflammatory disease?

The main criticism of the explanatory model of the theory of discomfort in depression is that there are a large number of cases in which no physical cause or sign of organic inflammation could be found in the patient.

However, according to this theory, it is argued that psychological stress processes can cause this inflammation just as any type of infection does, thus causing the symptoms of depression.

Experiencing high levels of stress over a long period of time has been linked to increased levels of pro-inflammatory cytokines. These, as explained above, have a direct effect on the levels of serotonin and other neurotransmitters related to depression.