“In the last two weeks, do you remember having a poor appetite? Did you sleep more than usual? Were you irascible? Have you felt almost daily that nothing made you happy? Did you feel tired all the time? Did you find yourself crying without knowing why? If you answer yes to several of these questions, be careful! You could be the victim of depression, a very common mood disorder that we sometimes tend to frivolise by mistaking it for a transitory state of sadness.
But the depression, as it is often colloquially abbreviated, is not an unimportant slump. Not much less. The Bulgarian philosopher and psychoanalyst Julia Kristeva, who currently teaches Semiology at the State University of New York (USA) and the Paris VII University Denis Diderot (France) suffered it in her own flesh, and describes it as “a abyss of sadness, of an incommunicable pain that absorbs us until we lose our self ”.
Francesc Artigas, Director of the Department of Neurochemistry and Neuropharmacology at the Barcelona Institute for Biomedical Research (CSIC-IDIBAPS), expands the definition: an effort. He is someone who has a hard time getting out of bed and going to work or college, going to dinner with friends or even visiting the doctor. “
“For those who suffer from it, life becomes unbearable. Our existence is full of small and large obstacles that we usually overcome in a natural way, but that the depressed patient is unable to face ”, comments Artigas. And he adds: “In other words, the depressed patient has a low resilience [a person’s ability to overcome traumatic circumstances] to stress. That is why he has anxiety, cries, suffers, sleeps badly, eats little, and finds no pleasure in anything he does. And that’s why, if you don’t find solutions, take an extreme measure: commit suicide to stop suffering. “
The worst thing is that, if you recognize yourself in this robot portrait, it is very likely that you will admit it only to yourself. Most people with depression do not tell about it, do not even go to the doctor and, of course, do not receive treatment. Why? Due to ignorance but above all, due to fear of stigma. “All, absolutely all mental illnesses are stigmatized in our societies, although they are as biological as any other ailment”, asserts a resounding Artigas. He attributes it to the fact that these types of disorders alter human behavior and, therefore, social relationships. And since the alterations in the brain that cause them are not known in detail, “the easy thing is to blame the sufferer.”
In the case of depression “it is common to say things to the patient like ‘Cheer up, man / woman, don’t take it so seriously! Do this, do that and you will see how you improve. ‘ But asking a depressed person to cheer up is like asking a Parkinson’s patient to win a 100 m race in front of healthy individuals of the same age ”, compares Artigas, who in 2015 was the first Spaniard to receive the prestigious Neuropsychopharmacology Award . which is awarded by the European College of Neuropsychopharmacology (ECNP).
“It is accepted that Parkinson’s disease has an organic basis, but not that other alterations of the brain that are equally biological in nature cause depression”, reflects this expert. Even the patient himself sometimes feels guilty, rather than sick.
The worrying thing is that we are talking about a disease that is reaching the dimensions of a global pandemic. At the moment it affects more than 300 million people around the world. But it will get worse if, as predicted by the World Health Organization, by the year 2030 depression becomes the leading cause of disability worldwide.
To understand the real magnitude of the problem, Artigas refers us to the international group for the study of the burden of diseases around the world ( Global Burden of Diseases Study Group ).
“The burden of each disease is calculated based on the number of years lived with disability due to that disease (YLD, acronym for years lived with disability)”, explains this Spanish researcher. Well, in that ranking, depression is the third disease with the highest YLD in women and the fifth in men . “This high burden of depression is due to its high prevalence, at least 10% in them and 20% in them,” adds Artigas. Or what is the same: one in ten men and one in five women will have one or more depressive episodes throughout their lives.
And that was before the covid-19 pandemic. A Canadian meta-analysis based on data from 55 international studies carried out between January and May 2020 has calculated that the prevalence of depression increased threefold after the new coronavirus appeared on the scene. “They are not definitive data, but it is clear that covid-19 has and will have a significant negative impact on global mental health,” confirms Artigas.
So that the diagnosis of depression (and its possible treatment) does not depend on people openly recognizing that their mood is upset, a team of scientists from the University of Alberta (Canada) has come up with an interesting alternative to the symptom lists. Namely: detect the disease from the sound of the voice . After collecting all the research that concludes that the voice tone contains information about our mood, they have taught a machine to identify when the way of speaking is typical of a depressed individual. Which, incidentally, is recognized for its monotony in the sentences, tension in the voice, slowness, hoarseness and erratic speech.
Written expression could also give away a depressive. According to a British study published in Clinical Psychological Science , the differences in the language of people with and without symptoms of depression are striking. To begin with, because they use a large number of adverbs and adjectives that express negative emotions, such as’ sad ‘,’ lonely ‘and’ fatal. Although the most characteristic thing is that they abuse the first person singular (I) and hardly use the third person (he / she). Another feature of depressive language is that words that express absolute magnitudes, such as ‘always’ and ‘never’, are much more frequent. That’s because depressed people see the world in black and white. Shades of gray are lost.
Patterns very similar to these are those identified on Twitter by Ferran Sanz, director of the Research Program in Biomedical Informatics at the Hospital del Mar Medical Research Institute (Barcelona). Analyzing the tweets that are published on the popular microblogging platform, he has confirmed the relationship between the predominance of the self and depression. “Although the analysis of tweets will never replace the diagnosis, it has potential as a complementary tool for the detection of depressive disorders,” says Sanz.
Nor does it seem like a bad idea to bet on detecting it in a blood test, as scientists have been trying for decades. The first to approach the target have been Eva Redei and her colleagues from Northwestern University (USA). Working with 64 subjects, half diagnosed with depression, they identified nine RNA blood markers whose levels are altered by the disease. Why this nucleic acid? Simply because RNA molecules are the messengers that interpret the DNA code and convey its instructions to cells.
What gave a definite boost to the work was that, after eighteen weeks of therapy, only in patients who had responded positively to treatment did these markers return to their healthy levels. Redei openly expressed his enthusiasm at the sight of the results, announcing that “for the first time there are indications that we can objectively diagnose depression as we do with hypertension, anemia or high cholesterol.”
Once the problem of diagnosis has been solved, there is another question to be answered: the physiological causes. Because, hard to believe, this ubiquitous disease is still a great unknown. “Over the years, various theories have emerged on the pathophysiology –analysis of diseases while symptoms occur– of depression, which most likely reflect partial aspects that affect multiple spheres of life, both at the affective level, as cognitive and somatic ”, Artigas explains when we asked him about this topic.
What seems indisputable is that it is associated with a significant chemical imbalance in the brain. The first theories pointed to the deficit of some brain neurotransmitters, such as serotonin, which intervenes in vital processes such as mood, perception, reward, anger or appetite. But serotonergic antidepressants, despite instantly increasing levels of the neurotransmitter, take weeks to work. Sign that this molecule is not the root of the problem, but probably a side effect.
“Subsequently, more emphasis has been placed on deficits of trophic factors such as neurotrophic factor derived from the brain or BDNF, neurogenesis deficits in the hippocampus, inflammatory and hormonal factors, etc.”, Artigas lists.
BDNF is a protein that, in its mature state (mBDNF), promotes the growth of neurons and protects the brain. However, there are two precursor or immature forms of the molecule that cause nerve degeneration and inflammation. Evidence suggests that excess psychological stress lowers mBDNF levels and, in the long run, can cause depression. Furthermore, studies conducted in China suggest that the severity of depression increases the less neurotrophic factor circulates in the blood. Another gold mine to find an objective way to measure depression.
On the other hand, research in animal models shows that depression significantly reduces the manufacture of new neurons in the hippocampus. But why? Lisa E. Kalynchuk and her colleagues at the University of Victoria (Canada) believe they have the explanation. Neurogenesis is an energy-consuming process, and this brings out what they consider to be the “real problem”: a malfunction of the mitochondria, the cellular power plants . The reasoning is logical: disrupted mitochondria would unleash a cascade of effects that could culminate in depression. If this is confirmed, we could have more effective antidepressant drugs that, at a stroke, return the mitochondria to normal. And, bye, depression!
When it comes to brain mapping of depression, there have also been significant advances in recent times. Neuroimaging techniques have identified that the disease is always associated with neuronal hyperactivity in ventral areas of the cingulate cortex , specifically the so-called Brodmann area 25 (BA25). It does not seem to be a coincidence since this cortical zone is connected with multiple brain areas whose activity it regulates.
Confirmation that we are on the right track comes from deep brain stimulation. This technique, which involves implanting electrodes within the brain and periodically launching electrical impulses that modify brain activity , has reaped benefits in resistant diseases such as chronic pain, Parkinson’s disease, and dystonia. Applying it in the aforementioned Brodman area, the symptoms of depression disappear in minutes. Still, it is so invasive that it is only used when conventional antidepressants fail.
The last great lesson psychiatry has received is that you don’t just have to look at the brain to understand how depression – and other mental disorders – is forged. The guts also influence, more specifically the bacteria that live harmoniously in our intestine, forming what is known as the microbiota. “It makes sense if we take into account that the access to the brain of the compounds that circulate in the blood is regulated by the blood-brain barrier, whose functioning is influenced in turn by products secreted by the intestinal flora”, concludes Artigas.
Specifically, the contribution of amino acids to the brain – among them, tryptophan and tyrosine, precursors of serotonin and norepinephrine, respectively – is regulated by the blood-brain barrier ”. In this way, not only does everything fit in, but the expectations are positive.
