When inflammation in the defense system explains depression

Unraveling the mysteries of the brain is a pending issue in 21st century Medicine. And it is diseases such as dementia, neurodegeneration and psychiatric disorders that put health systems and society in check. Mental health breaks the stability of a population that survives historical moments: pandemics, wars, economic crises…. And the cracks that lead to depression emerge.

As defined by the Spanish Royal National Academy of Medicine, we are faced with a “sad, depressed state of mind, lacking energy and vitality, sometimes accompanied by anguish, feelings of personal worthlessness and self-reproach”. According to the 2020 European Health Survey, the prevalence of depression in the population over 15 years of age in Spain is 5.28%.. Some data that is on the rise. And they reach 12% of women and 5% of men between 75 and 84 years of age.

These are high figures that unfortunately are the same in the rest of the world. The WHO estimates that more than 280 million people worldwide suffer from it.. Why is it so difficult to cure it with drugs? Perhaps, as pointed out by the professor of the Department of Psychiatry at the University of Cambridge, Edward Bullmore, it is because the way of approaching mental disorders is wrong. “We must prepare ourselves to have a new perspective in this field. A person who suffers from physical health problems also manifests mental health symptoms.”

Bullmore belongs to a disruptive current that for years has been trying to explain that these mood swings “are not just a psychological reaction to something that is happening in the body”. In his book The inflammation of the mind (Editorial Paidós) he develops this thesis that is well summarized in the subtitle of the manual: “A new and radical way of dealing with depression”.

This neuropsychiatrist, also considered a neuroimmunologist, advocates not separating body and brain in the approach to diseases. “Nature does not. They are two faces of the same coin”. This error that has dragged Medicine for centuries is responsible, in part, for the stigma that weighs on mental illnesses. “We have specialists in Cardiology, for the heart; in Neurology, for the brain; in Psychiatry, for the mind. This is how Medicine has been distributed for hundreds of years. But this is not how the human being is really organized.

And to explain this, the also leader of the Neuroimmunology of Mood Disorders and Alzheimer's Disease (NIMA) consortium decided to address this perspective in the book. “We need a culture change.”

The brain can suffer inflammation and trigger depressive symptoms. We feel bad for the blow, but also for what happens in that organ

Everything is based on the idea that the reactions of the immune system – “the army of our defenses” – occur when there is a problem in the body. But it's not just a local response, it puts defcon2 or even defcon3 in mode, so there are consequences beyond the damaged area.

-If you hit an elbow, you only see the damage in that place. How do we see the rest?

-Even if there is a problem in the elbow, which swells and turns red, there is a reaction of the entire immune system. If it were a country, the whole army would find out what happened. There could be a particular concentration of soldiers arriving at the point of the terrorist incident, but everyone will know that there is a problem in one part of the territory.. It is similar with inflammation. There may be a specific point, but the whole organism is on alert.

-This has to do with the fact that cytokines, among other substances, send inflammation signals through the bloodstream to all parts, including the brain?

-Clear. And the brain can suffer from inflammation and then trigger symptoms of depression, for example. We feel bad about the blow, yes. But also because there is something that happens in the brain that makes us feel that way.

And here is the real revolution of his theory. Until now, psychological discomfort was associated with a physical one, because it is normal to feel depressed in a situation that invalidates physical qualities. Mrs. P is the character Bullmore uses as an example in her book. A woman suffering from rheumatoid arthritis, with pain and difficulties in her day to day. Also, he has depression. And what do they have to do with each other? Well then, classical Medicine sentences like this: “Depressed? Wouldn't you be?”

The head of service answered a young Bullmore. As the gray-haired professor now relates, “30 years later, we began to see in a more scientific way the relationships between depression and inflammation, between the mind and the body, as I myself discovered some time ago in person after going to the dentist” .

-The example of your visit to the dentist shows that it takes a lot of organic damage to experience depressive symptoms, right?

-Clear! I went because I had an infected tooth. First I had a psychological reaction, it made me think about the passage of time, about getting old. But then another more rational. My immune system had come out to fight the bacteria responsible for my infection and therefore I was suffering from inflammation. That could make me not feel like doing anything for a while, I just wanted to get into bed.

It was a brief state that made him reflect on what would have happened if he had not gotten up the next day and had lengthened the time of sadness and laziness. And if so, you would have ended up at your GP who would diagnose you with mild depression and end up prescribing drugs. And it would be medicalizing in vain. In Spain, according to Health data, 34.3% of women and 17.8% of men aged 40 and over have withdrawn at least one container of antidepressant, anxiolytic or sedative-hypnotic.

-But, how is an inflamed brain?

-Today we have a lot of research in this field. First we have to develop all the tools to dispose of it.. Of the new technologies that allow the development of brain imaging diagnostic methods. Along with this, there are many advances in the field of analysis of the immune system through blood samples.. Everything has already been widely used in other areas of Medicine, for example, in autoimmune diseases.. But we have to develop our analytical standards and translate them to people whose main problem is a psychiatric disorder.

– Is it difficult to carry out research in mental health?

-Yes a lot. We are light years away from other clinicians, such as immunologists or oncologists. Much more research is being done on cancer, because it can obviously be lethal and reduce life expectancy.. But, mental health disorders cause much more disability, much more loss of productivity and quality of life than cancer.. And yet cancer gets much, much more research funding.

Bullmore's lament justifies the need to reverse the approach to mental health problems. “You have to open your mind, take into account other factors in psychiatric disorders. Society needs it.”

Mental disorders cause more disability than cancer, more loss of productivity and quality of life, but there is no investment in their research

Looking back, he remembers why at the age of 16 he already knew that he wanted to dedicate himself to something related to science and when he entered university he decided to study Medicine and later specialize in Psychiatry.. “I thought it was obviously the most interesting and exciting area because there was still a lot to understand and I found it very interesting.. I wanted to find a new way to address mental illness.”

30 years have passed since then, and that young man who was not in his thirties, has not witnessed those changes.. “Everything has been very slow, but I hope that, in the next hundred years, the new generations will find inspiration in my book and in our working groups to advance in this field,” he says.

But many barriers still need to be broken, says Bullmore. Perhaps, most importantly, “to stop considering the blood-brain barrier as the wall that separates the body and the mind”. Once again, a perfect metaphor illustrates this in his book: The Berlin Wall.. “Psychiatrists don't think about what's on the other side, we don't need to think about the rest of the body. I think that's partly because of the idea that people have that the blood-brain barrier is very rigid.”

Slowly, steps are already being taken towards its transfer to carry medicines with different techniques. How to carry chemotherapy with microbubbles or use ultrasound to find the target of Parkinson's. “It is not a question of destroying the wall, but of crossing it. And to integrate it into the whole, body and mind. A person does not have a head and the rest of the body, right?

Achieving it would mean being able to give an answer to those who wonder, as Bullmore was questioned years ago. “How do you know I have depression? How do you know there's a serotonin imbalance in my brain?” At that time, the professor in his first answers recited the serotonergic hypothesis of depression [imbalances of said substance in the hypothalamus].

Today it is clear to him that it is necessary to change the focus: “We should dare to think otherwise.”