Dr. Martina Melzer, published: 06/03/2022, updated: 02/20/2023

Autonomic nervous system (ANS)

ANS and Immune System

ANS and Endocrine System

What is the Cell Danger Response (CDR)?

The Psyche

Psycho-Neuro-Endocrine-Immunology. This barely pronounceable medical term means: your psyche, your emotions, your thoughts, are inextricably linked to your nervous system, hormonal system and immune system. All systems and organs influence each other. They are one. You cannot see them separately from each other.

In body-mind-brain disorders, also called mind-body syndromes, the interaction of these systems is out of balance. In my view, this leads to syndromes and disease patterns such as: ME/CFS, Long Covid/Post Covid Syndrome, Chronic Lyme Disease, POTS, fibromyalgia, irritable bowel syndrome, anxiety disorders, depression, (complex) PTSD, burnout and Post-Vac Syndrome. This imbalance also plays a significant role in MCAS, Ehlers-Danlos syndrome and small fiber neuropathy.

The first step toward recovery, in my experience, is to acquire knowledge, understand connections. Other strategies: the right mindset, brain training, inner work, lifestyle changes.

The autonomic nervous system (ANS) essentially consists of two major nerve cords: the sympathetic and parasympathetic nervous systems, both of which operate automatically and autonomously. The sympathetic nervous system is the activating part, and the parasympathetic nervous system, also called the vagus nerve, is the calming part. According to polyvagal theory, it has two main branches, called the ventral vagus, which is there for social interactions, among other things, and the dorsal vagus, which is important for rest and digestion, but can also initiate an emergency response from the body when life is in danger.

Together, they control, regulate and influence the functions of the internal organs and other body systems: eyes, lungs, thyroid, heart, stomach, intestines, liver, spleen, pancreas, kidneys, bladder, sexual organs, fatty tissue, hair roots, blood vessels, sweat glands, immune system, hormonal system. And besides, areas in the brain that perform vital functions: cardiovascular regulatory center, respiratory center, swallowing, sucking, coughing and sneezing center, digestion, vomiting center, tear formation, pupil size, urinary bladder emptying.

In addition, the ANS is responsible for warning us of danger, protecting us, ensuring our survival. The autonomic nervous system constantly checks whether we are safe or in danger. If it senses danger, it prepares us to fight for our lives (fight response) or run (flight response) in an emergency. This is what the sympathetic nervous system does. If the situation seems hopeless and fight or flight is futile, it puts us into into shutdown mode (collapse response). This is done by the older part of the parasympathetic nervous system, the dorsal vagus. We play dead. Sometimes playing dead can also help the attacker pass by and not scent us. There are a number of hybrid stages between these three forms of survival mode. People with body-mind syndromes are usually in an intermediate stage between very high sympathetic activation and very high parasympathetic activation, or oscillate between them.

While the sympathetic nerve originates in the spinal cord, the vagus nerve extends into the brainstem. The nerve messenger acetylcholine serves to transmit signals in both nerve cords. In the sympathetic nervous system, there is also adrenaline and noradrenaline. The precursor messenger of norepinephrine is dopamine. Norepinephrine and epinephrine bind to so-called alpha or beta receptors located on the organs. Acetylcholine binds to so-called muscarinic receptors. By inhibiting or activating these binding sites, the neurotransmitters control the target organs.

The central control site of the ANS is the hypothalamus in the brain. It is connected to virtually all brain regions and the central nervous system. The hypothalamus receives signals from the limbic system and other brain areas and sends signals to the pituitary gland, parts of the brain stem and the spinal cord. The main task of the hypothalamus is: to keep the organism in balance, to keep it healthy. For this purpose it controls the hormonal system, water balance, body temperature, food intake, cardiovascular system, activation or inhibition of the sympathetic or parasympathetic nervous system, sexual function, etc.

Chronic stress, adverse childhood experiences and trauma can throw the ANS out of balance.

Physical factors include: lots of sports, accidents, injuries, surgery, unhealthy diet, lack of exercise, illness, infections, vaccinations, childbirth.

Mental factors include: bosses, stressful job, school, college, job loss, divorce, relationship problems, physical/sexual/emotional abuse in childhood or adulthood, financial problems, information and news overload, marriage, caring for a relative, constant availability, lack of time, too many demands, character traits.

Environmental factors include: mold, chemicals, air pollution, contaminated drinking water, pesticides.

In most cases, no single factor is sufficient to cause lasting disruption of the autonomic nervous system. Several of the above examples must come together. Emotional factors are the most important.

The result is a malfunction of the ANS, dysautonomia, as doctors call it.

When immune cells or other components of the immune system detect a pathogen or other foreign substance that it considers potentially dangerous, it triggers an acute inflammatory response. This information is immediately sent to the brain. This happens primarily via the vagus nerve, whose numerous secondary branches all over the periphery "feel" what's going on. Eighty percent of the information relayed by the vagus goes from the periphery to the brainstem. But the sympathetic nervous system also picks up the "inflammation" information. Now the hypothalamus is activated and through it, among others, the nerve branches of the sympathetic and parasympathetic nervous systems that flow into the periphery.

Both are significantly involved in controlling and regulating the acute inflammatory reaction: The sympathetic nervous system communicates with all immune cells and organs primarily via the messenger substance norepinephrine, since they possess receptors for norepinephrine. If a pathogen, toxin or injury causes acute inflammation in the body, the sympathetic nervous system stimulates the immune system inital, which increases the inflammation. At the same time, the sympathetic nervous system tunes the entire body and organ functions to adapt to the acute event - for example, to provide energy and to shut down tasks that are not so important at the moment. Adrenaline and cortisol are released from the adrenal glands via the so-called HPA axis.

As mentioned earlier, the parasympathetic nervous system initially sends pro-inflammatory signals to the hypothalamus. This probably also triggers the feeling of sickness, the so-called sickness behavior, with fatigue, fever, pain, depressed mood. However, the descending nerve cords of the vagus nerve send an anti-inflammatory message. Receptors for the neurotransmitter acetylcholine are also found on all immune cells and organs. Thus, under normal circumstances, the vagus nerve ensures that inflammation subsides once the pathogen, toxin, or injury is removed. In this way, the nervous system, immune system and body return to balance - to their homeostasis.

Chronic stress and trauma overactivate the ANS and, as a result, the. immune system. An always activated immune system leads to chronic inflammation, which can be very mild ("silent") or very pronounced. It can occur anywhere in the body. The immune system consumes a lot of energy in the process, which is why the small energy power plants in our cells, the mitochondria, are exhausted at some point. We lack energy. Inflammation in the body also activates immune cells in the brain and central nervous system. More pro-inflammatory immune messengers, the cytokines, are found. This leads to inflammation in the brain. The longer autonomic nervous system and immune system are in disarray and other factors fit, so autoimmune reactions can occur. In classic autoimmune diseases, this leads to tissue damage. This is not the case in ME/CFS and related syndromes, studies show. Researchers speak of an autoimmune-like reaction.

Depending on the situation, the hypothalamus sends various precursor hormones to the pituitary gland. Depending on what information it has received from the hypothalamus, it in turn releases hormones that signal, for example, to the thyroid or adrenal glands whether they should ramp up or ramp down their hormone production.
The pituitary gland sends the hormone ACTH to the adrenal glands. These then produce the hormones aldosterone, DHEA and cortisol. This happens normally at different times of the day, for example, and the hormones perform their normal functions. Cortisol affects, among other things, the release of insulin and sugar metabolism, blood pressure, the immune system, inflammation, energy levels and much more.

When we are stressed, the hypothalamus responds very quickly to the appropriate signals from the autonomic nervous system and causes a lot of cortisol to be released acutely - as well as adrenaline. The body should thus be prepared for an acute dangerous situation, as already described, so that it can fight or run for its life in an emergency. We are full of energy. These in the past really dicey events we call today "stress". It is important that after the danger, when we are safe again, the release of cortisol, adrenaline and noradrenaline is stopped, we can rest - and replenish energy reserves. Because otherwise the hormones, especially cortisol, can do damage in the long run.

With chronic stress, to which we are all somehow exposed today, too much cortisol can permanently circulate in the organism. We are constantly under power, unable to switch off. The HPA axis gets out of whack and functions incorrectly. We are totally tired and exhausted, but still under power ("tired but wired"). In people with ME/CFS, for example, it can happen that they have much too high cortisol levels at the beginning and much too low later, or that there is too much cortisol available at night but not in the morning when we get up. Then we feel totally flat and exhausted in the morning, despite 14 hours of (non-restorative) sleep. One study found that people with ME/CFS had 50 percent smaller adrenal glands than healthy people. Cortisol levels are also altered in other conditions, such as anxiety disorders, fibromyalgia and depression, and even in what is called post intensive care syndrome. It keeps people who are in intensive care from getting back on their feet.

The HPA axis also controls the sex hormones testosterone, estradiol and progesterone. It is clear that if the axis is out of balance, this also affects these hormones and their functions. Particularly in women who have ME/CFS or a related syndrome, endometriosis or polycystic ovary syndrome (PCOS) often occurs in parallel. Female menstrual cycles and the ability to have children are also affected.
In addition to the hypothalamic-pituitary-adrenal axis, there is one that extends from the hypothalamus to the thyroid gland (HPT axis). It monitors our metabolism. If it doesn't function properly, it can trigger not only exhaustion but myriad other ailments that are very similar to ME/CFS and fibromyalgia. The tricky thing here is: thyroid levels can be normal, but the gland is still only functioning below average. This is called non thyroidal illness syndrome (NTIS). This is a protective mechanism controlled by the hypothalamus, which shuts down the thyroid gland and thus the energy metabolism. The body does this when its survival conditions are not optimal.

In addition, there is Hashimoto's thyroiditis, an autoimmune disease in which the body attacks the thyroid gland and it eventually loses its function. This results in hypothyroidism. This disease often occurs in parallel with ME/CFS, but of course could be an alternative cause to ME/CFS.

The dysregulated HPA axis also throws insulin and sugar metabolism out of balance. In people with dysautonomias like POTS and ME/CFS, blood sugar (glucose) often rides a roller coaster. It can rise way too high and then drop rapidly. Triggered by epinephrine, norepinephrine and cortisol, it shoots up even more and is subsequently depleted. This can also happen at night, leading to hypoglycemia during sleep. Some people with dysautonomia already have insulin resistance: the body cells that are supposed to absorb sugar from the blood shut down. However, this condition does not necessarily have to be detectable in laboratory tests.

In connection with the malfunctioning nervous system that is stuck in its survival mode, I must briefly mention the so-called Cell Danger Response (CDR). According to its discoverer, Dr. Robert Naviaux, CDR is an evolutionary mechanism that provides healing and recovery in the body at the cellular level after injuries and (life-threatening) dangerous situations. These situations include infections, psychological or physical trauma, lack of oxygen, stress, environmental toxins, accidents, among others.

These factors trigger a stress response in the body and this activates the CDR. It causes the cells to go into a hypometabolic state, so their metabolism is shut down, you go into a kind of hibernation. The central site of action is the mitochondria, the little energy power plants in our cells. Immune system, autonomic nervous system, metabolism, hormonal system, gut microbiome, gut nervous system, genes, sleep, behavior and thinking all adapt to this status. Naviaux lists some "symptoms" that accompany it: Social withdrawal; interrupted sleep; abdominal, head and muscle pain; sensitivity to light, sound, smell and touch; flu-like symptoms. CDR goes through various stages until the body is healed and fully functional again. Then the energy is back, too.

Naviaux suspects that in many chronic diseases, including ME/CFS, this healing cycle is incomplete and the body is stuck in survival mode. He says that the perception of danger and safety can be traced to and affects every cell and mitochondrion.

I think CDR is the molecular explanation for all the negative effects caused by an autonomic nervous system misdirected by stress. After all, the activation of fight, flight, submission, or freeze is for survival in a dangerous situation. If the organism is stuck in survival mode, it cannot heal and become healthy.

As a pharmacist, I have been influenced by orthodox medicine and have made exactly the same mistake. I also thought of my illness only in terms of organs and drawers, immersed myself in numerous studies. I wanted to dive right into the cell nucleus and lost sight of the whole body, which consists of trillions of cells. Especially because so many doctors thought I was a "psycho", thought "it's all in the head" or everything was "psychosomatic", I went into inner resistance. No, I have a physical disease, a neurological one, maybe even an autoimmune disease. In the meantime I see it all more differentiated. As I said, body, mind and brain are one unit.

I don't like the word "psychosomatic" at all. Not only because I was confronted with it so often during my years-long doctor's odyssey and was told "it's all psychosomatic" or "you have nothing" or "you have depression" or "you have too much stress". But also because I don't think the term is correct. Very many doctors want to tell you that a psychological problem triggers physical complaints. According to the motto: It's all in your head. But as I wrote above, brain, mind and body are an inseparable unit and they influence each other and always bidirectionally. So one should rather speak of "mind-brain-body disorder" or "body-mind-brain disorder". The order of the terms is arbitrarily interchangeable.

Axel Schweickhardt describes in the book "Psychosomatische Medizin und Psychotherapie": "Psychosomatics means that body and soul are two inseparable aspects of the human being, which are only distinguished for methodological reasons or for better understanding. This does not imply "linear" causality in the sense that mental disorders cause physical illness. That would lead to a dualism in which there are diseases with a psychological origin and diseases with a somatic origin."

Physician and polyvagal expert Deb Dana says, "Your autonomic state becomes your psychological story." By this she means: Our autonomic nervous system is constantly gathering sensory perceptions from the outside and inside world and sending the information to the brain. There it reaches the brain stem and from there the limbic system and other brain regions. A large network of nerves, extending through the limbic system with the thalamus and amygdala to the higher brain regions of the cortex, evaluates whether the incoming information means safety or danger. This all happens unconsciously and at breakneck speed, so that we can react automatically in the face of danger - and fight, flee or freeze. Depending on the status of the autonomic nervous system, consisting of the sympathetic and parasympathetic nervous systems, we feel and think. We get anxious thoughts, get angry or feel helpless and hopeless, see everything black. So our biology creates our mental state, our thought world, our behaviors.

Even though the first thing you think of when you think of emotions is the psyche, they are more of a biological thing. They are the result of our autonomic status, body sensations, organ functions, energy state and have a great influence on our thinking and behavior. They express themselves mainly through the muscles of our face and body. Quite unconsciously and intuitively we interpret the facial expression, voice, muscle tension and body posture of another human being - just like any other animal creature on this planet. This then puts us in fight, flight, freeze or in safety and connection. Accordingly, we unconsciously adjust our own facial expression, voice, posture and muscle tension.

If we feel connected and safe, we speak softer, brighter, smile, relax our muscles, have a calm and upright posture. If we are afraid, we tense all kinds of muscles, tear our eyes wide open, hold our breath, our stomach turns, our legs are restless. If we are angry and programmed to fight, we clench our fists, pull our eyebrows together, tighten our jaws, make ourselves big. If we feel helpless and at the mercy of others, we hardly make a sound, huddle together, lower our head, are stiff.

If we are sad, we cry, sob, are silent, huddle together. If we are disgusted, we feel sick, we tense our muscles and retreat, we contort our mouth, nose, eyes.

What I want to say with this paragraph: symptoms can be an expression of an external or internal injury, of a damaged organ, of a serious illness. But symptoms can also be bodily sensations and expressions of certain emotions and the autonomic nervous system. It is extremely important to have new symptoms thoroughly clarified by a doctor.

Physician, psychiatrist and trauma researcher Dr. Bessel van der Kolk names the emotions stored in the body that one experienced during a psychological or physical trauma, as well as the constant alarm mode of the autonomic nervous system, as (co-)causes of diseases such as: (complex) post-traumatic stress disorder, autoimmune diseases, chronic back pain, fibromyalgia, migraine, chronic fatigue, irritable bowel syndrome, asthma.

Physician and trauma expert Dr. Gabor Maté describes the completely underestimated influence of suppressed emotions, especially anger and rage, which one was never allowed to express as a child and adult, on numerous diseases. For example: multiple sclerosis, ALS, ulcerative colitis, Crohn's disease, ME/CFS, fibromyalgia, migraine, endometriosis, skin diseases, cancer, cardiovascular diseases. He says, "Repressed emotions and stress are major contributors to disease. And: that doesn't mean you are to blame for your illness!

Dr. Russell Kennedy has devoted an entire book to the topic of anxiety disorders, which he himself struggled with for decades. His message: anxiety is the worrying thoughts about the future, about potentially dangerous situations that could occur. However, anxiety originates in the body, in our guts, as a result of a permanent state of alarm of the autonomic nervous system.

Prof. Gregor Hasler lists a wide variety of "psychological" and "physical" diseases as possible consequences of disturbed gut-brain communication: Depression, anxiety disorders, Parkinson's disease, addictions, multiple sclerosis and other autoimmune diseases, ulcerative colitis and Crohn's disease. He says: You can become a psychopath if your gut is not functioning properly (I understand). And depression and anxiety disorders possibly arise from dysfunctional gut flora, as well as from a dysfunctional gut nervous system.

Psychoneuroimmunologist Prof. Christian Schubert describes how much the psyche and immune system interact with each other, how our emotional state affects the functioning of the immune system. Emotional stress can lead to heart failure, rebound herpes infection, trigger an asthma attack, promote cancer, and autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, and lupus erythematosus.

Dr. John Sarno, a physician, came up with the concept of what he calls "Tension Myositis Syndrome," or TMS. Prof. Howard Schubiner, also a physician and psychiatrist, now calls it "mind-body syndromes." He says that many syndromes and complaints are the result of stress in childhood, stress in adulthood, learned personality traits and suppressed emotions - especially anger pent up over the course of a lifetime.

He emphasizes that the syndromes and complaints are not imaginary, nor are they mental illnesses, but are simply caused by the unconscious part of our mind. In his opinion, all the symptoms are triggered by the autonomic nervous system. It is out of whack, he says, because too many negative, stressful or traumatic memories are stored in the amygdala. The amygdala is also called the fear center and is part of the limbic system. So Sarno assumed that primarily the mind messes up the brain and body, while Dr. Stephen Porges, founder of the Polyvagal Theory, sees the autonomic nervous system as the cause of a disturbed mind-brain-body interaction. As mentioned above: from my point of view there is no hierarchy here, all three systems influence each other bidirectionally.

Sarno counts among others the following symptoms and syndromes to the Mind-Body-Syndrome (if structural causes have been excluded!): Heartburn, irritable bowel syndrome, headaches, migraines, anxiety disorders, depression, obsessive-compulsive disorder, eating disorders, fibromyalgia, ME/CFS, all kinds of chronic pain, carpal tunnel syndrome, interstitial cystitis, POTS, tinnitus.

Psychologist Stefanie Stahl has devoted an entire book to the topic of beliefs and protective strategies. She explains how they come about, namely through our parents. So we can't help it that we are the way we are. We were made that way. One of the most typical negative beliefs of so many people is: I am not good enough. Others are: I am a burden. I am stupid and ugly. I have to be kind and good. Beliefs are something very individual and I advise you to find yours.

These beliefs affect our behavior and relationships because we develop so-called protective strategies. These are often rather unhelpful behaviors such as perfectionism, helper syndrome, beauty mania, victim thinking, withdrawal, striving for control, over-adaptation, narcissism and role-playing. Again, you need to figure out your personal protective mechanisms.

In his decades of practice, Sarno has found, as has Schubiner, that people with syndromes and chronic pain often exhibit certain personality traits. These include: Perfectionism, high expectations of themselves, self-critical, constant feelings of guilt, high sense of responsibility, always wanting to help, being worrying, anxious, sad, angry. Such people put themselves under permanent pressure, quite independently of the pressure from other people. These characteristics are also listed by the other book authors I mentioned above.

Alex Howard also presents in a book what personality traits people with chronic fatigue and ME/CFS typically have: ambitious, perfectionistic, helping, anxious, controlling. He explains how such traits contributed to his own ME/CFS and how they fostered the boom and bust cycle, or activity-crash. He has treated numerous people with chronic fatigue and has consistently observed that these traits have prevented people from recovering. They kept drifting back into their old learned behaviors, especially when they were feeling better. Then the disease got worse again.

That is psycho-neuro-endocrine-immunology, summarized as briefly as possible.

PS: Of course, I research and check everything I write here as well as possible. Nevertheless, I am only human and make mistakes. In addition, I may draw completely different conclusions as someone else would. Simply because they fit my story. But every story is different.

Important: The content on this page is for informational purposes only and is not a substitute for talking to your doctor or other therapist. The content reflects my personal experiences, research and findings that have helped me and that I therefore want to share. However, in your personal case, completely different things may play a role and other things may help. Please talk to your doctor or therapist before making any decisions that affect your physical or mental health. Also important: I don't want to convince anyone of anything here. Rather, I want to point out possible ways that hopefully can help some people to improve or overcome their ME/CFS or other syndromes.

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