According to a new study from the Netherlands Institute for Neuroscience, people with depression they have fewer active microglial cells. The document was published in the magazine Biological Psychiatry.
Depression: what it means to have fewer active microglial cells
Depression contributes significantly to the global burden of disease and is a leading cause of disability worldwide. Information on the pathophysiology of the disease and new therapies are urgently needed, as treatment resistance is common and occurs in up to 30% of patients. Previous research has shown that patients with depression have altered levels of inflammatory markers.
Additionally, depression has been linked to chronic inflammatory diseases, such as rheumatism, inflammatory bowel disease and multiple sclerosis. These findings suggest that brain inflammation may play a role in depression. But it’s true?
A new study by Karel Scheepstra and her team, supervised by Inge Huitinga and Jörg Hamann, looked at postmortem human brain tissue from people with depression. This brain tissue comes from recently deceased donors who donated their brains to the Dutch Brain Bank for Psychiatry (NHB-Psy).
And what did they find? A certain type of immune cell in our brains, called microglial cells, are less active in people with depression. Contrary to expectations, the opposite of inflammation actually occurs: immune cells are suppressed.
Microglial cells are important because they maintain contact points between neurons (synapses), thus helping neurons communicate efficiently with each other. In addition, microglial cells constantly scan the central nervous system for damaged neurons, synapses, and pathogens. In samples from people with depression, only microglial cells near neurons showed reduced activity.
The team then investigated whether neurons send signals to microglial cells during depression, making them less active. And this indeed turned out to be the case.
Karel Scheepstra (researcher involved in the study and who also works as a psychiatrist at UMC Amsterdam) says: “During the study we used fresh tissue immediately after death to isolate microglia and compare them between depressed people and controls. We saw abnormal microglia in depressed patients, with the greatest abnormalities seen in patients who were most depressed just prior to death.”
“Interestingly, the abnormalities were only seen in the gray matter and not the white matter of the brain. This suggests that there is a probable interaction between microglia and structures located in gray matter: neurons and synapses.”
“We also looked at the type of alterations. We’ve assumed for years that depression is associated with brain inflammation, but now we’re seeing just the opposite: not neuroinflammation, but rather an immunosuppressed type of microglia. We’ve called them “depressed microglia” and wondered how exactly that is possible. The CD200 and CD47 proteins are found in brain cells and synapses.”
“They interact with microglia and are, so to speak, a sort of ‘don’t eat me signal.’ What we saw was that these proteins were elevated, resulting in microglia being suppressed, thus preventing them from clearing damaged connections.”
“Depression is thought to have something to do with a change in neuroplasticity: the ability to make new connections between neurons. A relatively new antidepressant is esketamine, a drug that intervenes in this process and ensures that more connections start growing again. In this study, we demonstrate that there is a disturbed neuron-microglia interaction. The next step would be to see what exactly the consequences of inactive microglia are for maintaining and forming connections between neurons.”
“If we know where things go wrong in the process, this can provide targets for new drugs. Can we make these microglia more active again? And what effect does this have on the course of the disease? For now, we have shown that the brains of people who were depressed during their lifetime show altered cellular activity. This gives us a better understanding of what goes wrong, which we can then build on.”
In Europe, according to the ISS EpiCentre: “In Europe, major depressive disorder alone accounts for 6% of the total burden of suffering and disability linked to disease. According to the World Health Organization, this disorder currently ranks third in order of importance for the burden it causes and, if not tackled, will rise to second by 2020 and first by 2030.
From a public health point of view, therefore, major depressive disorder is one of the most serious problems and one of the major sources of care burden and costs for the National Health Service.
The more episodes of major depression you’ve had, the easier it is to have new ones. About 50% of people have a second episode after having a first episode of depression; after three episodes, the probability of having a fourth is 90%.
In its extreme manifestations, major depressive disorder can lead to suicide, as a result of which around 4,000 people die in Italy every year. In Italy, according to the estimates of the Esemed study, every year over one and a half million adults suffer from a depressive disorder.
Depression can occur at various ages, and different tools can be used as indicators of the frequency of the problem among young people, adults and the elderly. As far as adults are concerned, the Passi surveillance system detects what is reported by people between 18 and 69 years of age, obviously excluding diagnostic purposes and only for the purpose of focusing the attention of health professionals on the importance of services aimed at this type of suffering in the population considered socially and workingly “active”.
In the Passi system, core depressive symptoms (symptoms of depressed mood and loss of interest or pleasure in all, or nearly all, activities) are captured using a validated test, the Patient Health Questionnaire-2 (Phq-2). The Phq-2 is a screening tool derived from the Patient Health Questionnaire-9 with satisfactory sensitivity and specificity.
In a clinical setting, the Phq-2 makes it possible to identify people with probable depressive disorder to be referred to specialist services, only in this context and with more accurate diagnostic tools will it be possible to diagnose a depressive disorder. In the surveillance field, the Phq-2 allows to identify people with probable depressive disorder.
With the collected data, prevalence and characterization measurements of “probably” depressed people with chronic pathologies, lifestyles and other factors, including social factors, detected in the same system are carried out.
In the period 2008-2011, depressive symptoms are reported by a non-negligible share of the adult population: about 7% of people between 18 and 64 years of age. Those who suffer the most from it seem to be older people, women (9%), those who declare that they have many economic difficulties (16%), people with a lower level of education (12%), those who do not have a regular job ( 9%), those who live alone (10%) and those who are affected by at least one chronic pathology (14%) among those investigated in the surveillance”.
According to the WHO, depression: “It is a common mental disorder, from which an estimated 5% of the global population suffers. It is characterized by persistent sadness, a lack of interest or pleasure in activities, even those previously considered pleasurable; […] it is an important cause of disability. There are psychological and pharmacological treatments”.
Nicola Conti, psychotherapist, declared: “Depression means something far beyond being down in the dumps: it is a question of not thinking about the future, but about nonsense. What one actually does is settle down in nonsense and the risk for those who are next to them or who assist them is to collude with the mechanism, when instead it must be undermined”.
” Especially for family members assisting a family member with depression is enormously complicated, because it involves keeping the measure 24 hours a day. Among other things, if you are a parent or a partner it is obvious that you feel motivated, therefore following a course of psychotherapy it could be useful for learning how to manage the person”.
“First of all, the risk, both for those who work in close contact with patients (such as the figure of the psychotherapist), and for those who experience these situations as a friend or family member, is of being “infected”. In this case, the emotional contagion, especially if you are a particularly empathic person, literally gives you the same sense of uselessness. This is why setting boundaries is absolutely necessary.
All the more so in cases where you find yourself in front of a non-interactive person, and for whom, in order to stimulate them, you are inclined to take “charge of their efforts” encountering continuous frustration: so much applying yourself to work out their problems, looking for a key to understanding them and then they take them apart with total lack of participation, as inability. Their part is missing. An uncomfortable silence for those who want to help, whether it’s a psychotherapist or a friend.
Meanwhile, here too the danger is getting stuck between compassion/commiseration (“poor thing”) and insistence (“get a move on”). This type of situation leads to an asymmetrical relationship, because you place yourself above us, as if that person depended on us. We must be encouraging, but without trying to replace her/him.
We consider that he lacks a temporal perspective, he has a real planning block, he is unable to see the future. This doesn’t mean that he shouldn’t be helped to feel responsible for the possibility of being able to change.
It is certainly deadly to be next to these people. Assuming the Red Cross attitude, which leads to self-sacrifice and unconditional acceptance, often has the semblance of self-realization.
The last thing to do is to attack: “didn’t you hear from me?”, because depression already takes the form of self-accusation. So maybe it’s time to bring the conversation back to yourself, explaining how you feel, demonstrating your displeasure about it. You have to take some space, without attacking.
The more you dig, the more you realize that it’s not sadness, but anger that they turn towards themselves in a severe internal dialogue. The challenge for therapy is to bring them to the awareness that they are angry with themselves, especially when it comes to people with difficult backgrounds.
And the real achievement would be to turn this anger into action. As for those who are next to them every day it is certainly wrong and annoying with phrases such as “make a move”, “force yourself out”. A listening and understanding attitude is much more helpful.
Nicola Conti helped us understand that there is no formula, it is an experimental search for balance. For those who find themselves next to those suffering from depression, it is like walking on quicksand, in which one sinks sacrificing one’s identity day after day.
This is neither fair nor useful. Just as it is not to attack, judge or put pressure, although at times the situation may seem unsustainable and it is absolutely human to blurt out. The keyword therefore seems to be honesty, towards oneself and towards the family member/friend in question.
What do we want from that person? Is it something he is able to give us? What can we offer? These are all questions to ask yourself when you fear that you have reached a point of no return. Trying to break their disesteem, their unwillingness alone, can be very risky and lead to continuous frustration. There’s still a long way to go, but in our small way, respecting and respecting each other can help.
It is a process of growth for both, and at the expense of both, but fundamental to moving forward with ourselves and for them, abandoning an infinite loop, to build real perspectives”.
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