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The theory of the malaise of depression: what it is, and how it explains this disorder

The theory of the malaise of depression: what it is, and how it explains this disorder

April 19, 2024

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

Despite the high incidence of this disorder or emotional condition, there are still major disagreements within the scientific community about the true cause of this. One of these these theories is the depression malaise theory , which we explain throughout this article.

  • You may be interested: "Major depression: symptoms, causes and treatment"

What is the theory of the malaise of depression?

Also known as the inflammatory theory of depression, this explanatory model of endogenous depression disorders created by UK doctor and researcher Bruce G. Charlton In the year 2000, he tries 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 kind of infection, our own organism emits an inflammation response by means of which a series of hemodynamic alterations are carried out, of the lymphatic levels and the release of a series of agents such as cytokines, neuropeptide histamine, etc., with the purpose of restoring the health of our body.

In addition, along with inflammation a psychological phenomenon known as Behavior of illness appears . This type of psychological response is characterized because the person experiences a series of feelings of tiredness, somnolence, anhedonia and cognitive alterations, all this symptomatology coincides with part of the clinical picture of major depression.


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

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

Finally, Charlton himself proposes that the true effect of antidepressant drugs when it comes to alleviating the symptoms of the disease is in the analgesic effect that most of these have, so that by decreasing organic inflammation, symptoms of depression also decrease.


On what evidence is this explanation based?

Although at first it is somewhat complicated to believe that a depression is not caused by an external factor that provokes this response, the theory of discomfort is based on a series of empirical evidences that support it.

1. Coincidence of symptoms

As mentioned above, the symptoms of major depression coincide in many aspects with those of the disease behavior, which tends to appear when we suffer some kind of physical illness.

In these cases symptoms such as fatigue, decreased physical energy or feelings of anguish and sadness They appear with the objective that our body stays at rest and recovers as soon as possible.

2. The effect of cytokines

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

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

Also, 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

The antidepressant drugs exert an effect on the levels of the cytokines, specifically the decrease. Therefore, this reinforces the idea that the main cause of endogenous depression is in the effects that these proteins cause in the organism.

4. The inflammatory response system and depression

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

In addition, a clear relationship has been established between the activation of the inflammatory response system of our organism and depression; since it is continuously activated during this disorder.

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

5. Antidepressant action of anti-inflammatory drugs

Finally, some research has discovered that the administration of anti-inflammatory medication in some cases of endogenous depression not only significantly improves the symptoms of this, but also does so in greater proportion than some antidepressants.

What if there is depression but not inflammatory disease?

The main criticism of the explanatory model of the theory of malaise in depression is that there are a large number of cases in which a physical cause could not be found or signal of organic inflammation in the patient.

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

The experimentation of high levels of stress over a long period of time has been related to an increase in the levels of proinflammatory cytokines. Which, as we have explained previously, exert a direct effect on the levels of serotonin and other neurotransmitters related to depression.


OCD & Anxiety Disorders: Crash Course Psychology #29 (April 2024).


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