There is new evidence that depression is not just a mental disorder, as blood tests that have shown the presence of inflammation in patients with depression with treatment options tailored to the needs of each individual patient. I was a young doctor in 1990 when I met a patient with rheumatoid arthritis [1]. Ms. B told me quietly and in clear terms that she had identified all squares marked on her depression. When I told the chief doctor in charge of her condition, he said, "Well, I'd do that if I were her place, right?" And changed the subject. He meant that her mood was a logical reflection of her present situation, where she was suffering from a disability and was waiting for a future in which her health and mobility would deteriorate. She was "deceptively" depressed because she was thinking, and teasing, what it meant to have an inflammatory disorder. So there was nothing we could do as doctors, it was a psychological, not a physical, issue of psychiatry.
Ms. B's symptoms, which were closely intertwined with her experience of arthritis, were divided into psychological and physical. After diagnosing Ms. B into two parts, we began to treat her physical disease "swollen joints" in a different and completely separate from her psychological illness of depression and exhaustion. We used the medical language of immune cells to treat inflammation, while a different team of doctors at another hospital used serotonin and psychotherapy to treat depression [2].
"Depression" is a loose expression meant by many meanings. The clinical meaning of the day is similar to that of the old Greek melancholy or blackened doctors, the syndrome of sadness or mood decline, low energy and the ability to feel joy or "lack of pleasure" (Anhedonia) and low appetite for sex and food, pessimistic expectations about the future, and the guilt of the past Self-indulgence in thinking that can lead to self-harming behavior or suicide.
Epidemiological data indicate that the prevalence of depression is about 10% among the population
It is certainly depressing to be sick. But what if depression is not a psychological disorder? The idea that Mrs B might be depressed because of the inflammation, not because she was thinking about inflammation, was something I did not think of in 1990. Such an idea was to be a medical leg even if you were smart enough to imagine her existence then.
But this is a serious investigation at present, and the cornerstone of developing neurodegenerative neuroscience. It not only reflects a new way of looking at this disorder but is also prepared in other ways to treat and monitor it and even take new measures to prevent it from appearing in people whose life experiences develop it.
New pathology pathology
Epidemiological data indicate that the incidence of depression is about 10% among the population, and that the percentage rises among patients with rheumatoid arthritis where up to 25%, or who suffer from inflammatory bowel disease or psoriasis or chronic lung disease or any inflammatory disorders or immune diseases Other self. Advocacy groups, such as the National Association of Rheumatoid Arthritis in the United Kingdom, note that psychological symptoms such as depression, exhaustion and "brain clutter" are key aspects of the unmet needs of many patients with physical illness.
To prove that depression can be caused by inflammation in the body requires a lot of evidence, but it also requires more: a radical shift in thinking, because it goes beyond one characteristic of Western thinking: the deep fault line that isolates thoughts about how the body works Mind.
Steroids are among the most powerful anti-inflammatory drugs currently available; they mimic the effects of cortisol
Even in our time, in 2019, Ms. B's experience is not considered unfamiliar. Many patients with inflammatory disorders consult with specialists such as rheumatologists who may identify symptoms of depression but do not feel they know how to treat it or understand how it relates to the swollen joints they feel they can treat. The physical separation of psychological symptoms is not surprising given the division of mind and body in Western medicine, but it is surprising given that most physicians have direct clinical experience in the effects of anti-inflammatory drugs on mood improvement.
Steroids are among the most powerful anti-inflammatory drugs currently available; they mimic the effects of cortisol, the anti-inflammatory hormone produced by the human body, against the effect of immunosuppressants called cytokines. It is well known that steroid therapy results in rapid and dramatic improvement in mood and energy (although these effects are not generally long lasting, and the use of excessive steroids can be associated with depression and psychosis).
One of the anti-cytokines, Remeced, has made significant progress in the treatment of inflammatory disorders in the past 15 years. It targets and inhibits inflammatory hormones and usually has an antidepressant effect within a few days of treatment.
The antidepressant effect of anti-inflammatory drugs in Comborid Depression patients is exactly what you would expect if their depression was directly caused by inflammation. But this is not usually explained in this way. Instead, remission is seen as an imaginary response: patients could have improved in an equivalent way if they thought they were taking remykad while taking a harmless alternative.
New neuroimmunology assumes that the inflammatory response of the immune system involves changes in the way the brain works
Randomized trials of placebo, anti-cytokine and antibodies in patients with arthritis, psoriasis and inflammatory bowel disease have often shown an improvement in mood. But there is still debate as to whether the mental health effects of cytokine antibodies are a psychological reaction to their benefits to physical health. Patients become less depressed because they have less joint pain, less swelling and easier movement. In one way or another, the antidepressant effects of anti-inflammatory drugs in depression have been interpreted as a function of the mind.
The collapse of the Berlin Wall in the brain
Until relatively recently, the brain was considered to have an "immunity": the immune system could not reach it. [1] [2] The brain was shielded behind the cerebral hemorrhagic barrier, which consists of tightly encapsulated endothelial cells lining the blood vessels in the brain, which compare its immunity to the Berlin wall. Just as the Berlin Wall broke through, the cerebral blood barrier penetrated. It has become increasingly clear that there are many channels of communication between the immune system and its nervous system, and it is no longer absurd to believe that they are communicating with one another. They clearly do so all the time, and have significant implications for our health and resilience in a hostile and competitive world.
New neuroimmunology assumes that the inflammatory response of the immune system involves changes in the way the brain works, leading to a behavioral response. As inflammation often causes an increase in body temperature, it can often result in lower energy levels and behaviors that seek pleasure.
Animal experiments show that if a mouse is infected with a bug, its behavior changes as it becomes less active, less energy, less social, and less favored than sweetened water, as if it has found a taste less sweet than usual. This syndrome, which is similar to the behavioral features of depression, is called "disease behavior or behavior". It appears in a wide range of creatures including human sage. Pathological behavior does not begin from the infectious germ, but through its immune response. A mouse injected with cytokines will usually exhibit the same pathological behavior as a mouse with a bacterium.
Cytokines can pass through the cerebral blood barrier quite easily, there are enough large gaps between endothelial cells lining the walls of blood vessels to allow proteins such as cytokines to spread from blood to the brain. Even the circulating white blood cells can actively help to press the endothelial cells and reach the brain. Other channels of communication are sensitive to changing cytokine levels in the body and can send electrical signals directly to the brain such as the vagus nerve [3].
Not every patient with major depressive disorder does not have abnormal levels of cytokine or C-reactive protein
Inflammation causes depression
Depression is a common complaint among inflammatory patients, but the link between inflammation and depression is still unclear among patients with major clinical depressive disorder [4]. It is puzzling that the Fifth Statistical and Diagnostic Manual of Psychiatry does not place inflammatory disorders as a diagnosis in patients with major depressive disorder. Although studies from the 1990s have consistently found that levels of inflammatory proteins, including the protein known as C-reactive protein and cytokines, are significantly higher in patients with major depressive disorder than in healthy individuals [5].
The difference in levels of blood proteins in patients with major depressive disorder and healthy individuals is not significant compared with the higher levels of these proteins in arthritic patients. Not all patients with major depressive disorder need to have abnormal levels of cytokine or C-reactive protein. About a third of patients with major depressive disorder also suffer from low-grade inflammation. There are many possible explanations for this fixed fact: this may mean that depression causes inflammation or that inflammation causes depression or that both are caused by a third external factor. If the inflammation causes depression, we expect to find the evidence of infection first. Many studies have evaluated patients repeatedly and confirmed that infections can predict depression.
In southwest England, 14,000 people born in 1991 had a frequent assessment from birth to study their natural development. At the age of 18, there was a marked increase in depression among those who had high levels of cytokine in the blood when they were nine years old. Another study of British civil servants over 50 found that those with higher levels of C-reactive protein who did not experience depression when first evaluated in 2004 and 2008 had significantly higher rates of depression when reassessed in 2012. In both groups, the disease has been debilitated for several years.
Other studies have investigated the sequence of events over shorter time periods. For example, patients with hepatitis who did not suffer from depression before receiving antiretroviral therapy via cytokine interferon had a significant increase in the risk of depression after about six weeks of treatment. The health of young people after placebo was healthy and again after typhoid vaccination showed relatively mild and transient symptoms of depression after 48 hours of vaccination. A clinically treated inflammatory shock such as interferon therapy or typhoid vaccination can predict subsequent depression over time periods ranging from days to decades.
The peripheral inflammation that occurs in different parts of the body disrupts the function of the emotional brain
The primacy of inflammation may be consistent with depression, but it is not conclusively confirmed. It is still not clear how the inflammatory signal in the blood causes changes in the brain that can lead to mood swings and depressive behavior. Animal experiments suggest that such a series of events is conceivable in humans, but it is more difficult to measure the state of immune cells or neurons in the brain of a living human as in the brain of mice.
Brain scan methods - such as functional magnetic resonance imaging (fMRI) - show that patients with major depressive disorder who have higher levels of C-reactive protein in their blood have decreased their contact strength between the components of brain circuits or networks known to be important in emotional therapy and mood disorders. The peripheral inflammation that occurs in different parts of the body disrupts the function of the emotional brain. Despite the accuracy of MRI, it can not provide information on individual neurons or inflammatory state of immune cells in the brain. In fact, there is no good way to measure inflammation in the human brain at present; this is one of the current obstacles to determining the role of body inflammation in human encephalitis which in turn generates changes in mood and behavior.
Stress is the basis of inflammation and depression
There are many potential sources of inflammation that can cause major depressive disorder of the patient. The immune system responds to many internal and external factors that can affect the condition of inflammation, such as increasing levels of cytokine in the winter months and decreasing in the summer. Hormonal changes in aging and post menopause are associated with increased inflammation. Obesity is also strongly associated with inflammation. Fatty tissue is rich in fat cells [6]. All these and other factors known to increase inflammation are known to increase the risk of depression.
The most prominent source of inflammation that causes major depressive disorder is stress. Social stress is the biggest risk factor for depression; major life events such as the death of a family member or close associate, divorce and job loss, as well as the awkward social roles of adults such as caring for a loved one, increase the risk of depression in the following weeks, months or years. Stress in childhood, such as early separation from parents, predicts depression decades later.
Ideally, genes control the behavioral response to inflammation and infection in animals and humans
Interestingly, there is growing evidence that the relationship between stress and depression is mediated by inflammation, where stress causes inflammation, which in turn leads to depression. In a long-term study of a group of neonates in New Zealand, children who suffered from abuse or adversity at the age of eight had increased levels of inflammatory proteins in their blood at the age of 21. A study of stressful teachers and flexible teachers found that teachers who suffered from occupational stress produced more cytokines than flexible teachers. All the teachers pumped more cytokines within an hour of the stressful task of delivering a speech. There is a lot of evidence that stress causes inflammation in animals.
Why does the immune system make us depressed?
The answer to this question goes back to Darwin, like all the questions "Why?" In biology. There must be a logic that makes depressive behavior part of the inflammatory response that enhances our ability to survive. The benefit of depression for survival or reproduction is not crystal clear. Patients with major depressive disorder are usually poorer, have less stable relationships, have fewer children and have lower lives than their non-depressed counterparts. According to the British National Health Service in 2016, serious psychological illness, major depressive disorder, bipolar disorder and schizophrenia led to a 12-year life expectancy reduction. It is clear that the major depressive disorder is not [natural] because it helps the human race survive in the 21st century. But the depression-like behavior of a response to inflammation can have helped our ancestors survive in the distant past when they were more susceptible to infectious diseases.
Energy and activity decline may be energy-saving to fight infection. Social withdrawal may be a "patient" fever of competitive stress and the rest of the tribe fever of potential infection. Intermittent anxiety and sleep may make the patient more alert and less susceptible to predation. Even our predecessors may have evolved to suffer from inflammation not only in response to infection but in anticipation of the threat of infection. Social attitudes such as conflict or competition for resources that are likely to lead to violence and trauma with a high risk of infection can be the cause of a preventive inflammatory response, including pathological behavior.
If so, genes that increase the risk of major depressive disorder today must include genes that produce cytokines or other proteins from the immune system. Ideally, genes control the behavioral response to inflammation and infection in animals and humans. Unfortunately, our understanding of heredity of depression has not reached this level of progress yet.
The development of antidepressants has been in search of a magic pill that is applicable to all people with depression
We know that depression extends in families and is genetically inherited. Only until 2018, the first accurate and reliable data identified 44 "gene for depression", although they collectively accounted for less than 10% of the total risk for major depressive disorder. The discovery of the genes of major depressive disorder has been slow, as thousands of genes have been shown, each of which has little effect. Scientists also had to examine very large numbers of DNA for patients and healthy individuals (the comparison group) to identify genes of major depressive disorder that are important among all other genes in the genome.
Now that we have DNA for hundreds of thousands of patients, we can identify some genes associated with major depressive disorder. Many of these genes make proteins in the brain and some are related to the immune system. The gene most closely associated with the major depressive disorder is olfactomadin 4, which controls the inflammatory response to gastric infection. This is what you expect if you believe in evolutionary interpretation, but this conclusion requires a more accurate analysis than mere data to be sure.
Unified treatment is not for everyone
What difference could further research make in verifying whether inflammation sometimes caused depression for treatment and prevention? One obvious innovation is the use of anti-inflammatory drugs as antidepressants for patients with major depressive disorder and post-traumatic stress disorder. Numerous clinical trials of anti-inflammatory drugs have provided circumstantial evidence for their antidepressant effectiveness. On the other hand, there have been a handful of small studies on the ability of nonsteroidal anti-inflammatory drugs to treat major depressive disorder. When analyzing all data, there is no clear evidence that they act as antidepressants.
However, studies suggest something that is likely to be important; The development of antidepressants has been in search of a magic pill that is applicable to all people with depression. Antidepressants are given to any depressed patient such as fluoxetine and the associated selective serotonin reuptake inhibitors on the grounds that they work effectively on average. But selective serotonin reuptake inhibitors will not be effective for all major depressive disorder cases.
Studies suggest that blood tests will become more important in psychiatry than in the past
Anti-inflammatory interventions will never be the solution for all patients with depression. At present, there are new antidepressant therapies, including macrophage replacement diets, electromagnetic stimulation devices designed to change the function of emotional brain circuits, and drugs that primarily work on neurotransmitter glutamate rather than serotonin receptors such as ketamine [7]. The future is a set of therapeutic options, but how do we know which treatment is most effective for each patient?
A therapeutic revolution?
When scientists who ran an anti-inflammatory drug trial for depression such as nonsteroidal drugs such as Reemikide analyzed their data, they found that some patients responded better than others. The beneficial effects of treatment were greater in patients with major depression who had higher levels of C-reactive protein in their blood before starting treatment. Which means that treatment of depression by anti-inflammatory drugs was better for patients with depression who had a greater inflammation, which is not surprising. In fact, what is surprising is the improved way outcomes refer to future depression.
Studies suggest that blood tests will become more important in psychiatry than in the past. The next wave of clinical trials of anti-inflammatory drugs to treat depression will likely measure the biological indicators of inflammation to predict patients who are more likely to respond to antiretroviral therapy.
Many interventions of varying effectiveness and prevalence are now being used to relieve depression. Ranging from purely psychological training such as brain training to surgical operations, such as vaginal nerve stimulation where a subcutaneous device is implanted to deliver electrical impulses to the vagus nerve, which makes an effort to produce an anti-inflammatory reaction. This procedure is risky and is reserved for patients who have not responded to other treatments. Vital indicators of the state of the immune system not only refer to people who are likely to respond to a particular therapeutic approach, but also to the progress of treatment. This is a standard practice in other areas of medicine, and it will be a major breakthrough if psychiatry can do the same.
There is growing evidence that suffering from childhood distress is associated with increased inflammatory proteins in adults
I predict that in the future we will use vital indicators of the immune system, including C-reactive protein, cytokines and others, to identify those patients suffering from depression caused by inflammation. This will allow us to provide them with a more personalized treatment plan with interventions aimed at treating inflammation. It may be possible to take advantage of the immune system not only to treat depression but also to prevent it. Child abuse or trauma is a strong predictive risk factor for depression that may appear decades later. It has long been known that the immune system has an uncanny memory of exposure to biological threats, such as childhood infections. For example, survivors of potentially fatal childhood infections, such as measles, retain an immune memory that enables them to respond strongly if exposed to the virus again later in life. Could this apply to social threats to survival in childhood?
There is growing evidence that suffering from childhood distress is associated with increased inflammatory proteins in adults. There is detailed evidence in animal experiments that stress in early life such as separation from a parent can imprint a marker on the genome that causes a tendency towards an inflammatory animal response to late pressure. In other words, the immune system of the mouse can carry a long-term memory of childhood stress, making it more susceptible to infection (and depression) when it reaches.
If this also appears to be true for humans, it may be possible to use vital signs of immunological memory for children who have been abused or in distress in identifying children at risk of mental health disorders later in life and are therefore likely to benefit from preventive programs. Scientists may eventually discover ways to reprogram the immune memory of abuse so that survivors do not carry the risk of depression for the rest of their lives.
Immune Soldiers: Acute cells and microglia
The most important function of the immune system is self-defense against foreign objects of the body, a classic example of which is the immune response to infection. We live in a world full of germs, foreign microscopic particles of the body that can harm or kill us. If we have a serious microbial, the immune system is ready to deal with the situation. Acute cells reveal and destroy bacteria.
Depression is very common indeed, about one in four people suffers from a major depressive episode sometime in their life
The first immune response to infection is usually inflammation; when the macrophages detect the presence of an infectious germ, they activate. Cells move towards the bacteria to try to contact them and then swallow them and digest them. In spite of the efficiency of the cells, the bacteria can multiply very quickly and exceed a number. To help fight the potentially huge number of foreign factors, the help cells call for the release of proteins called cytokines in neighboring blood vessels that spread throughout the body and attract other cells to promote direct immune response against the bacteria.
In the days and weeks following infection, cells and other specialized immune systems are involved. For example, lymphocytes - a type of white blood cell - may increase the production of antibodies, proteins that can help thin cells recognize and kill the same type of bacteria more quickly if they occur in the future.
Once the inflammatory signals from the body reach the brain, they are often picked up by the brain's rich cells called microglia and amplified. Microglia are stimulated by cytokines to produce more cytokines in a positive vicious cycle that can have adverse effects on the function of neighboring neurons. The neural connections between neurons do not adapt so quickly to changing stimulus patterns. Cytokines also make neurons less prone to proliferation and more susceptible to death. In addition, inflammation causes some neurons to reduce or release serotonin, the neurotransmitter believed to play a major role in depression. The resulting changes in inflammation collectively lead to behavioral inflexibility, the hallmark of depression.
Inclusion of the inflammatory agent in the treatment of depression
Depression leads people to withdraw socially. Depression is very common indeed, about one in four people suffers from a major depressive episode sometime in their life. Depression touches every family on this planet.
Many anti-inflammatory drugs already exist in the market, but none have been shown to have antidepressant effects.
If you know that you have an inflammatory disorder, such as rheumatoid arthritis or Crohn's disease, and you are also suffering from depression or fatigue, talk to your doctor about your psychological symptoms as well as the physical symptoms you experience. Standard treatments for depression such as selective serotonin reuptake inhibitors and psychotherapy can help in clinical depression, but many patients with physical disease do not use these therapies. Your doctor may refer you to a clinical psychologist or psychiatrist. Consider any antidepressant treatment options suggested by your doctors, communicate with others and share experiences with them.
If you are depressed but do not have a major inflammatory disorder, low levels of inflammation may contribute to your depression. A simple blood test of the C-reactive protein or white blood cell count can indicate the level of inflammation your body is experiencing. If the blood tests are positive, try to determine the cause of the inflammation and eliminate it, common possibilities include gingivitis, obesity and social pressure.
Many anti-inflammatory drugs already exist in the market, but none have been shown to have antidepressant effects. There are many ways to treat non-drug-based depression, including yoga, meditation, dieting and vaginal nerve stimulation, but none have been approved as a treatment for depressive symptoms of inflammation. So be careful, ask conclusive questions about the evidence for any treatment. Soon there is no risk of practicing yoga or refraining from specific nutrients from your diet; but it is still worth asking if this will change the levels of your body's proteins or inflammatory cells. Whatever course of treatment you choose after consulting with your doctor, keep track of your inflammation levels through repeated blood tests. Check your treatment if the degree of inflammation in your immune system remains high.
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Margins
[1] Rheumatoid arthritis is a chronic inflammatory disorder that attacks the immune system of the joints, causing inflammation and damaging joints, and can infect other places beyond the joints.
[2] Serotonin is a neurotransmitter that plays an important role in regulating the human mood. It is also called the hormone of happiness and sexual desire. It also plays a role in migraine and depression.
[3] Vaginal nerve or Vagin nerve (Vagus nerve): It is the only nerve that arises in the brain and ends away in the digestive system.
[4] Major depressive disorder (MDD): Also known as major depression, unipolar depression or clinical depression occurs when a person experiences one or more major depressive episodes. The major depressive disorder (single seizure) is diagnosed after a single shock. Depression without periods of obsessive depression is sometimes referred to as unipolar depression, because the mood remains low and does not rise as high as in bipolar disorder.
[5] C-reactive protein is a protein found in the blood at levels that rise in response to the inflammatory state.
[6] Acute or plasmid cells: Cells derived from single cells contribute to non-specific immunity and cellular immunity in vertebrates.
[7] Glutamate The neurotransmitter is a chemical secreted by nerve cells to send messages and can interact with light.
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Translation (Alaa Abu Rumaila)
This report is a translation from: Psychology Today and does not necessarily reflect the location of Medan