This post goes out to those who are unknowingly deep in the throes of mast cell activation and/or brain inflammation.
Though our culture is only starting to consider psychiatric conditions as inflammation of the brain, if you or someone you know has panic attacks, depression, mood swings, ADHD, brain fog, chronic fatigue, PTSD, autism, cognitive issues or even dementia, then you know the destruction neuroinflammation plays in people’s lives.
Tweaking neurotransmitter functioning, the primary role of modern conventional psychiatry, isn’t the same as treating inflammation in the brain. While psychotropic medications may help lessen symptoms (and can be life saving), they don’t address root causes including inflammation. In those with high immune reactivity, they may even trigger an inflammatory response themselves.
In this post, I’ll do my best to lay out the science as well as speak to the personal experience of brain inflammation. Because this topic requires explanation, I’ve tried to make it easy to jump ahead to find areas of interest. First some definitions:
Inflammation is a good thing. It’s a protective response to injury or infection. It helps remove the problem (toxin, infection) and start tissue healing.
Neuroinflammation is when the central nervous system (the brain and spinal cord) is involved.
Neuroimmunology - the study of this interface between the immune system and the central nervous system.
Neuroimmunoendocrinology - the study of the interface between the immune, central nervous and endocrine (hormonal) systems. These systems can influence each other in many directions, but for now, know that we have a stress hormone from the brain that activates the immune system to act on the brain (and the body).
Psychoneuroimmunoendocrinology - the study of how psychological and emotional stress can cause a hormone to be released from the brain (in an attempt to increase cortisol) that activates the immune system to inflame the brain (and body). When you hear, “stress causes inflammation” - that’s what they’re talking about.
What’s Happening at a Cellular Level?
Meet what I think are the three most important players when it comes to brain inflammation and thus psychiatric conditions. Later I’ll explain how they work together to cause symptoms, and how we can calm them down so we can heal and eventually thrive.
1 - Mast Cells
- Part of the immune system - they mediate immune, allergic and inflammatory response
- Everywhere in the body, but especially concentrated in areas in direct contact with the outside (skin, respiratory, digestive and urinary tract)
- Sensors - they sense what is going on in the tissues
- First responders when the body perceives a threat (toxins, infection, etc)
- They act fast (resulting symptoms occur quickly after a trigger)
- Great communicators - they have granules/ bags with many inflammatory mediators that when released do many helpful and potentially destructive things
- Those mediators communicate with a lot of other cells and tissues which is why they can cause so many seemingly unrelated symptoms throughout the body and brain
- Can be triggered to release those mediators by toxins, unwelcome microbes, chemicals, heat, cold and emotional stressors, among other things
- Can be triggered by CRH (see below) - a stress hormone from the brain
2 - Microglial Cells
- Also part of the immune system, but in the brain
- Job - remove damaged neurons, waste and things that aren’t supposed to be there and to keep the brain healthy
- Activated by mast cells
- Can be activated by CRH (stress hormone from the brain described next)
- Too much activation means too much cleaning up (excessively scrubbing any part of your body leads to inflammation and then tissue destruction- in this case brain cells/tissue)
3 - CRH Corticotropin Releasing Hormone (or Factor)
- A hormone released from part of the brain when we are under stress (physiologic or emotional)
- It’s also released from mast cells
- There are receptors for CRH on mast cells and on microglial cells - when it hits those receptor it activates those cells to do their thing which is to create inflammation
This helps explain how emotional stress causes “inflammation” and why lowering inflammation in the body and brain requires lowering stress in our lives and our stress response (and why I’m glad I’m a psychiatrist). In short, supplements, medication and dietary changes alone are not enough
- RCCX theory that suggests that about 15-20% of us have a mutation in an enzyme in our stress hormone pathways. This seemingly results in us having more CRH released when our body (or brain) is under stress, which means more mast cell and microglial activation leading to more inflammation. It also means we will be more prone to brain related symptoms and certain health issues and, therefore, need to be more intentional about lowering our stress response, as well as avoiding toxins and keeping our microbiome healthy.
These three players are essential. All is good until the burden or threat is greater than our ability to manage it. Examples would be if there is:
- A lot of toxicity (chemical, metal, or from mold, yeast or other microbes),
- Unwelcome microbes that aren’t easily removed (lyme, a virus, mold, yeast overgrowth) or
- If we are chronically stressed, have a traumatic event, or have the dysregulated stress response that comes with inadequate or disrupted early attachment or and more often...
- A combination of any of these.
These “stresses” call for more cortisol and to get more cortisol, the brain releases more CRH/ Corticotropin Releasing Hormone, which tells the adrenal glands to make more cortisol. This increased CRH (which again binds mast cells and microglial cells) leads to more mast cells being activated - dumping their mediators which activate more microglial cells (in the brain) resulting in brain inflammation and disrupted neuronal connections. Chronic inflammation can lead to cell and tissue death which is what we call neurodegeneration. The most common example is dementia.
While there is certainly evidence that there is a genetic vulnerability to mast cells becoming overly active, I and others would argue that toxicity (especially mold toxicity) tends to take it to another level.
Mast cell activation occurs in asthma, allergy, arthritis, cardiovascular disease, interstitial cystitis, psoriasis, atopic dermatitis, cancers and metastasis, endometriosis, obesity, ulcers, prostatitis, periodontitis, irritable bowel syndrome and inflammatory bowel disease.
Research, however, is also showing the role of mast cells in traumatic brain injury, multiple sclerosis, Parkinson’s disease, dementia, Alzheimer’s disease, stress conditions, sleep disorders, migraine, pain, ADHD and autism.
TYPES OF MAST CELLS
Mast cells are everywhere. We have 2 types, the mucosal type (lining of the gastrointestinal, respiratory and urinary systems which have “mucosa”) and the connective tissue type (in those tissues that hold us, our organs and our blood vessels together, including our skin). Because they are especially concentrated in places with direct contact with the outer environment (skin, GI tract, bladder, sinuses), they’re our first line of defense against toxins and unwelcome microbes. This is why the more common mast cell symptoms involve the skin, GI tract, sinuses, lungs and bladder.
MAST CELL ACTIVATION
Though patients and parents of patients contact me for their brain related symptoms, such as depressed mood, anxiety, inattention, restlessness, insomnia, agitation, mood, swings, intermittent personality changes or even mania, most also have other physical symptoms of mast cell activation. I’m not sure how much of this is because my practice attracts those with complex illness or because I simply ask about these symptoms - symptoms they might not think to mention. Nonetheless, one does not to have a plethora of physical symptoms to be suffering the consequences of brain inflammation.
MAST CELL ACTIVATION SYNDROME/MCAS
Those with Mast Cell Activation Syndrome have many signs and symptoms related to the activation of mast cells. Their symptoms are unpredictable and varied.
Common triggers which activate mast cells to release their mediators are:
- specific foods and drinks (especially alcohol, high-histamine and/or high carb foods)
- temperature extremes, high altitude, drops in barometric pressure
- airborne smells including perfumes, detergents, chemical smells, or smoke
- exercise or exertion
- emotional stress
- hormonal changes (especially during adolescence, pregnancy and women's menstrual cycles)
- electromagnetic fields / EMF (such as from cell phones, wifi, smart devices, and more)
- drops in barometric pressure
- excessive histamine (due to allergens, undermethylation, DAO insufficiency (due to a mutation in an enzyme that breaks down histamine from food in the GI tract.
MAST CELL SYMPTOMS
As you'll see below, there are many symptoms. While triggers can vary from person to person, so can symptoms. Triggers and symptoms can be unpredictable and vary from episode to episode.
Appetite swings - including excessive appetite after beginning to eat
Episodes of low body temperature
Temperature (hot/cold) sensitivity
Sense of being cold all the time
Difficulties with anesthesia
Unexplained medication reactions
Nausea and/or vomiting
Difficulty swallowing, throat tightness
diarrhea or constipation
Gastrointestinal pain or discomfort
Bloating and gas of irritable bowel syndrome
Anaphylactic reactions - ie. difficulty breathing, itchy hives, flushing or pale skin, feeling of warmth, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting.
Enlarged lymph nodes
Chemical intolerance - ie. fragrances or off-gassing in stores
Reactions to certain foods or drinks
Odd (or exaggerated) reactions to insect bites or stings
Sensitivity to sunlight or bright light
Conjunctivitis, “bloodshot” eyes
Sinus infections or problems
Shortness of breath
Sudden drops in blood pressure
Tachycardia (racing heart rate)
Skin lesions or sores
Skin feels on fire
Swelling & inflammation
Joint, bone pain
Fainting /Varying degrees of fainting
Vertigo or problems with balance
Unexplained weakness - “jelly legs”
Numbness & tingling in face and extremities
Persistent body/tissue pain
Intense anxiety or panic attack
Agitation or anger
Problems with memory
Other signs that may be less acute, but are nonetheless related:
Enlarged liver or spleen
Difficult menses (females)
Osteoporosis and osteopenia (including young patients) (m)
LIFE WITH MAST CELL ACTIVATION SYNDROME / MCAS
Multiple Systems, Multiple Specialists
If you have MCAS, you may have strange symptoms, and/or you may have a lot of symptoms that by themselves would not be of concern. You may just think it’s bad luck. Either way, you can’t put your finger on the problem and neither can the psychiatrist, the dermatologist, the neurologist, the ENT, the pulmonologist, the cardiologist, the urologist, the gynecologist, the allergist or the ophthalmologist who each look at just one part of your body.
Without answers, you may conclude that in some way you are the problem - it must be anxiety or psychological issues at play. After all, you seem anxious and depressed. And likely you are - and not just because you're physically sick, or because you’re demoralized by the medical system, but also because your brain is inflamed like other parts of your body. You eventually decide seeking help causes more harm than good. The fatigue leaves you moving through sludge. The brain fog keeps you from being able to organize your thoughts enough to try to solve problems or to make plans.
The Illusion of Control
If you have even recognized that there are triggers, you become seduced by a seemingly level of control. Just when you think you have identified and removed the trigger, the rug is pulled out from under you and you’re hit again with what feels like the flu - headache, body aches, depressed mood, fatigue, inattention and whatever mast cell symptoms plague you. Only after the fog clears, if it clears, are you able to wonder about triggers. When you’re not blaming yourself for your symptoms, you’re trying to figure out what else you could avoid or do to prevent them. You become consumed with your health. Not because you’re a hypochondriac, but because your limbic system is sensing a problem - a danger. And you’re trying desperately to figure it out.
Relationship to Your Body
Your body is not only defying you, it’s triggering you. With every unusual symptom comes a reminder that things aren’t right. That your tests results show nothing gives you no solace. How long will it be before the MS or early onset dementia or other yet to be diagnosed neurological condition is advanced enough to show up on tests. Your mind looks for answers and lands on extremes. You think you're worried because of the symptoms and if the symptoms were gone, that your worries and fear would be too. It never occurs to you that the anxiety might be just another symptom from the same source as the palpitations or the itching and that one isn’t necessarily or only leading to the other.
Relationship to Others and Work
How can you be so reactive to so many things? When did you become one of those people who has everything wrong with them; one who can’t harness enough energy or interest to stay connected with friends or even easily engage with those they love. One who has so many abilities, but no fuel, no motivation, and at times not even an ability to care. Caring requires energy. The sick irony is that you don’t look sick. You look normal. You don’t even have a diagnosis to tell people. You may feel alone even with those you love.
Relationship to the Future
After being knocked down figuratively and literally so many times, you’re afraid to feel hopeful. Will things ever change? You hope they will, but all the paths (the doctor’s appointments, the avoidance, the dietary restrictions) you’ve taken have only led to shame, isolation and further suffering. If you have had mast cell activation and brain inflammation, you have likely said to yourself, “I don’t want to live like this anymore,” when you were in the throes of an episode. I have no doubt that there are many individuals, if not most, who have taken their lives, never knowing that at the root of their suffering was a dysregulated immune system and at that moment of their deepest despair their mast cells and microglial cells were causing their brain to be inflamed. They couldn’t imagine that despair would pass (with the subsiding of the episode) or that this type of inflammation can be treated.
INSIDE MAST CELLS - MULTITUDE OF MEDIATORS
As I said earlier, mast cells contain granules (little bags) of ready to go inflammatory mediators. These messengers communicate with other cells and tissues which is another reason there are so many symptoms. You may recognize the names of some of these mediators: histamine, tryptase, chymase, tumor necrosis factor-alpha (TNF-alpha), serotonin, heparin, proteoglycans and vascular endothelial growth factor (VEGF). And if that list isn’t long enough, another source adds the following inflammatory mediators: IL-1beta, IL-8, IL-33, chemokine, ligand 2, CCL3, CCL5, GM-CSF, metalloproteinase (MMP’s), ROS, substance P, dopamine, TGF-beta, corticotropin-releasing hormone (CRH), neurotensin, prostaglandin D2, leukotrienes, proteases tryptase and chymase.
You’ll likely recognize a couple of these neurotransmitters - serotonin important for improving our mood and lowering our anxiety and dopamine important for mood and focus. Perhaps this explains why right before becoming sick, many people will feel especially good and focused or why some children with autism can have great clarity and increased speech right before they become sick. This might too explain when some people have mood swings from high to very low...very quickly.
OUTSIDE OF MAST CELLS - RECEPTORS
Mast cells not only release inflammatory mediators, they also have receptors for many of those mediators including CRH (which again is a stress hormone released from the brain, but also from other mast cells). So, when mast cells “degranulate” or dump out the contents of those granules, those mediators can communicate with other mast cells. When mast cells are activated, lots of things can be released to fight threats, but when they're persistently activated (because of a persistent threat) some of these mediators can destroy surrounding tissue.
EXAMPLES OF EXAGGERATED IMMUNE RESPONSES
Though it’s not so hard to imagine how an exaggerated immune response could cause someone to breakout into hives, have an asthma attack or even go into anaphylaxis after eating a peanut, it’s less obvious how an exaggerated immune response affects the brain. Consider the similarities between how one might feel if they have the flu (fatigue, brain fog, down mood) and if they have depression. They’re not so different. One is just lasting much longer. The similarities between anaphylaxis and panic attacks are even more dramatic.
Anaphylaxis - a mast cell mediated allergic response that occurs within minutes (or even up to 30 minutes) after exposure to an allergen (like a peanut).
flushed or pale skin
Low blood pressure (hypotension)
Constriction of your airways and a swollen tongue or throat, which can cause wheezing and trouble breathing
weak and rapid pulse
Nausea, vomiting or diarrhea
Dizziness or fainting
Panic Symptoms come on suddenly and can be triggered by certain situations.
- Shortness of breath
- Nausea and/or abdominal cramping
- Racing heart rate
- Chills or hot flashes
- Tingling sensations on the skin
- Chest Pain
- Tunnel vision
- Agitation or Aggression
So yes, while a peanut in one person can trigger anaphylaxis, an emotional trigger (ie. a sensation associated with a traumatic event, or an upsetting thought) can trigger mast cell activation and thus a panic attack. Despite the classic understanding of panic, it is very likely that a some people having panic attacks are reacting to physiologic triggers (ie.something they ate or inhaled) as opposed to psychological triggers.
WHERE THE IMMUNE SYSTEM & BRAIN MEET
Blood Brain Barrier and Gut Blood Barrier
When mast cells are stimulated they disrupt and release mediators that increase the permeability of what we call the Blood Brain Barrier (BBB) and Gut Blood Barrier (GBB).
The blood brain barrier is the barrier between our blood (which is carried throughout the body through blood vessels) and our brain. If you are an unwelcome toxin or microbe that has been ingested and you make your way through the gut blood barrier, into the blood and then up and through the blood brain barrier, the neuroimmune system is going to try to get rid of you. When the body has more toxins or unwelcome microbes than it can manage, there can be an exaggerated immune response impacting surrounding brain tissue.
Mast cells can also recruit other inflammatory cells and activate microglia (the immune cells in the brain). Though they're there to clean up unwanted dead cells and repair brain tissue, if they’re getting too much activation, they will release their own inflammatory mediators causing local inflammation and disrupted connections between neurons. If this goes on too long, nearby neurons will die which leads to neurodegeneration which can equate to the beginning of dementia. This is why there is a strong correlation between brain related disorders in younger people, ie children with ADHD, or adults with depression, PTSD, head trauma and later dementia.
While there is detailed, complicated and not terribly reliable testing for mast cell activation, I rely on in-depth questionnaires, a thorough history and a response to treatment as my guide, including:
- Detailed family history - usually there is evidence of mast cell activation related diagnoses. Fitting with RCCX theory, joint hyper-mobility (being flexible, double jointed, etc) in an individual or their family, is a red flag for mast cell activation.
- Very detailed “review of symptoms” - including all the symptoms above (and others that might point me in other directions)
- Very deep timeline - listening for early attachment disruption, emotional or physical trauma, including head trauma, environmental and toxic exposures, evidence of infections (Lyme, bartonella, etc).
- Because there is such a strong association with mold toxicity, a detailed environmental history is part of the timeline - if the person has ever lived, worked or spent extensive time in spaces with water damage (not that it’s always known)
- Inquire about triggers - if known
- Education, education, education. This is a double-edge sword. On one hand, it typically helps the person step outside of their symptoms and watch what is going on. They can realize that inflammation usually will pass, and that treatment can help to lessen their symptoms while we identify what is causing the inflammation in the first place. On the other hand, learning that one’s symptoms may be due to certain triggers such as certain food, or weather changes, etc, if someone has not already started to realize this, can lead to a level of vigilance that is problematic in of itself and even be triggering.
- Avoiding known triggers (for that person) - this could be hot baths, overeating, skipping meals, perfumes, big box stores, a narcissistic family member
Stabilize mast cells (so they’re not releasing all those mediators) - There are a number of interventions that can help with this. Sometimes layers of various interventions are needed.
- Access the vagus nerve (which helps stabilizes mast cells)
My favorite 2 supplements for stabilizing mast cells are:
- Quercetin (with or without Bromelain) - if taken 30 minutes before meals can stabilize mast cells in the gastrointestinal tract, so that eating itself isn’t leading to a level of mast cell activation.
- CBD oil - has been shown to help with depression, sleep, anxiety and pain, likely in part because of it’s mast stabilizing effects.
- Natural supplements - Mast-ease, Perimine, AllQluer
- Medication - Ketotifen, Cromolyn sodium
Block Histamine Receptors - If we could completely stabilize mast cells, we wouldn’t need antihistamines, but we do both to provide as much relief as possible. Histamine is just one of the mediators that mast cells release, but one that can further trigger mast cells to become activated. It can cause a lot of well known physical symptoms (skin issues, upper respiratory allergies), but also brain fog, fatigue and depression, especially for those who are undermethylated and because of this don’t break down histamine very well.
- Antihistamines (to block H1 receptors) - While many people with simple seasonal allergies can benefit from one 24 hour antihistamine, those with mast cell activation often can benefit from one twice a day or even three times a day. Surprisingly to many, this can help with brain fog, fatigue and even addictive type behaviors that histamine seems to drive. This can be a good tool to use initially while we identify and treat root causes.
- H2 blockers (to block H2 receptors) - which decrease stomach acid (ie. Zantac and Pepcid). Though not an approach I typically use, I mention it, because it is a common approach to treating mast cell activation.
Remove Sources of Histamine and Inflammation
Lower allergen exposure:
- Air purification (even if simply making your own $25 one with a box fan, air filter and duct tape.)
- Allergy covers for bed and pillow
Anti-inflammatory, and if necessary, histamine lowering dietary changes
- Sugar is inflammatory for everyone for a number of reasons
- Gluten and Casein - most people with brain related symptoms can benefit from taking these out of their diet
- Any other known food that one is reacting to.
There are foods that are especially high in histamine. Some people with mast cell activation will feel better removing these or taking a DAO/Diamine Oxidase supplement to breakdown histamine in the GI tract prior to a high histamine meal.
- Products of fermentation are high in histamine - ie. wine and other forms of alcohol, vinegar (in a lot of sauce type products, ie. ketchup, mustard, mayo, etc. soy sauce, yogurt, kefir, kombucha)
- leftovers, especially left over animal protein - beef, chicken, pork, fish, etc,
- beef (because it goes through an aging process) is higher in histamine than chicken
- Avocado, cinnamon, citrus, tomato products are also high in histamine
- See histamine ratings for specific foods
- Lower allergen exposure:
- Address Toxicity. In my experience, mold toxicity, because of the way it disrupts the immune system is the most common cause of mast cell activation. Because removing mold toxins (and other toxins) and treating mold colonization or other biotoxin related illness (Lyme, bartonella, etc.) can trigger mast cell activation, stabilizing mast cells and blocking histamine receptors, for some people, can make the treatment move along more smoothly.
- Address Digestion & the Microbiome. Undigested food in the lower digestive tract can be a source of fermentation, toxicity and inflammation. Some individuals can benefit from support with digestive enzymes and a supplement called Betain HCl. If mold toxicity is present, which again in my experience, usually is, then removing mold toxins and treating yeast and mold in the digestive tract become the priorities. Many individuals can’t tolerate probiotics or anti-fungal herbs, supplements or medication until the mold toxins are starting to be removed with mold toxin binders.
- Address Nutrient Status - Because I’ve written about copper overload, undermethylation and pyrrole disorder in other posts, I won’t focus on those here, but know that rarely does someone have mast cell activation or nutrient imbalances in isolation. Those who are vulnerable to nutrient imbalance and those with mast cell activation are overlapping (if not the same) populations. In fact if you look closely at the list of pyrrole symptoms you will see that most are similar to those of mast cell activation ( and connective tissue symptoms). It is arguable that pyrroles are actually the waste product of the weakened enzyme (21 hydroxylase) that 15-20% of us may have. It does have a pyrrole structure in it. As for methylation, we need methylation to break down histamine. If you are periodically being slammed with histamine because of mast cell activation and you are undermethylated and thus don’t break it down well, then you likely would be symptomatic before someone who is not. It is not uncommon to be be undermethylated, then have mold toxicity which leads to mast cell activation.
And last, but not the least....
Address the Hormonal Stress Response - It’s easy for one to hope that supplements and medication will do all the work, and then not take seriously, the idea of lowering stress in their lives. If people don’t heed this in the beginning, they often will learn that their healing is dependent on them addressing the faulty rewiring that can occur as a result of mast cell activation and brain inflammation. On the other side of all of these health issues, most people find that they have disassembled and rebuilt their lives In ways they never would have but for becoming sick. Self-care becomes a priority along with attention to diet, sleep and exercise (as tolerated). Healthy relationships with appropriate boundaries becomes the new standard. Work that might have once been stressful and mostly ego promoting is replaced by work that is more satisfying and meaningful.
- Neural Retraining. This treatment isn't specific to mast cell activation. One program in particular is the Dynamic Neural Retraining System, created by Annie Hopper. A similar program that I have less experience with is the Gupta Program Brain Training. Both are based on the understanding of neuroplasticity and our ability to essentially rewire our brain to strengthen pathways that are less triggering for us. Even before addressing toxicity, there can be dramatic results.
- Befriend Your Body that you have felt at odds with and triggered by for some time. The body is where we ultimately find calm (as opposed to our head) - yoga, breathing, stretching, walking, dancing or any form of movement.
- Practice Gratitude - this is part of rewiring the brain - it helps us scan our days, lives for the good. The more of this wiring there, the less room there is for fearful, vigilant and triggering wiring that can be inevitable for some with mast cell activation.
- Learn and Practice Embracing Uncertainty. This may sound like a spiritual approach. It is. As long as we think things need to turn out a certain way, we are creating stress in our lives and secondary inflammation in our bodies (and brain tissue). Yes, we can set goals, do our hard work and have our desires, but hold them gently, don’t grasp too tightly. Stay open and curious of what will unfold.
- Learn to be Mindful and Present - Use whatever practice works for you. Learn to meditate, do art, sing, do anything that opens your mind and moves you away from relying too heavily on detail thinking.
- Exercise your right hemisphere - again give your left hemisphere, which hones on every detail, a rest. There are a number of feel good strategies in my last post.
- Access the Vagus Nerve - which I look forward to writing about in a future post.
THE INFLAMED COLLECTIVE
People in families, workplace settings, schools or even larger communities where there is a shared toxic exposure can be unknowingly dealing with consequences of collective brain inflammation. I have little doubt that many marriages have ended because of brain inflammation. It’s not a stretch to see how living in our increasingly toxic and stressful world could be contributing to a collective that is less happy, less focused, less engaged and with greater suffering. Mast cell activation and brain inflammation aren’t new. They’re just becoming increasingly common as can be seen by the dramatic escalation in associated medical and psychiatric conditions.
THE PIONEERS (from my perspective)
MAST CELL ACTIVATION
Dr. Lawrence Afrin (MD) wrote the pioneering book,“Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity.” He and the mast cell community that follows his work are especially focused on the diagnosis and treatment of mast cell activation (and seemingly less on root causes such as mold toxicity or even a stress hormone pathway vulnerability). If you want to dig deeper into the physiology and available testing, I would highly recommend his book.
Dr. Theoharis Theoharides’ (MD, PhD), Professor of Immunology and mast cell researcher at Tufts University was the first to show that mast cells can be activated by CRH/corticotropin-releasing hormone, which is key in understanding the onset of disease or worsening of disease when under stress.
Dr. Sharon Meglathery (MD), a psychiatrist and internist described RCCX theory - a brilliant and complex theory that explains how some (15%-20%) of us are wired for mast cell activation because we have a weakened 21 hydroxylase enzyme) due to a range of mutations on the gene for it). Because of this, we have more CRH being released when under physiologic or emotional stress. This theory (in addition to connecting a number of other dots) drives home the importance of addressing inflammation by addressing this stress response in those with psychiatric and chronic complex medical illnesses.
MOLD TOXICITY & MAST CELL ACTIVATION
Dr. Neil Nathan (MD) is a pioneer in the treatment of mold toxicity and complex illness. He is also the author of “TOXIC - Heal Your Body from Mold Toxicity, Lyme Disease, Multiple Chemical Sensitivities, and Chronic Environmental Illness,” and my mentor. He and many others in the environmentally acquired illness community are not focused on RCCX theory, and find mold toxicity to be the most common root cause of mast cell activation. They also find that when mold toxicity is treated (which can take time) mast cells typically settle down and the inflammation (in the brain and body) become less of an issue. That being said, interventions that lower the stress response, such as DNRS are regularly prescribed tools for treating mast cell activation while, or even before, directly addressing mold and other forms of biotoxicity.
FOR THE READER WITH BRAIN INFLAMMATION &/OR MAST CELL ACTIVATION:
It’s always my hope that sharing some of what is being learned will help someone out there reconsider the stories they have about themselves, their symptoms and even their lives. And, it is my hope that the next time someone reading this, has a panic attack, an episode of depression, a tantrum out of the blue, severe brain fog, fatigue or even a suicidal thought, that they’re able to pause and be curious instead of being swept away by their faulty beliefs in that moment. Even if you don’t remember anything I said about mast cells, microglial cells or CRH, I hope you remember the term brain inflammation. I hope you can consider what you’re feeling isn’t a failing on your part, but instead, the way your immune system is telling you there’s a problem that needs to be addressed. And lastly, I hope you remember that despite brain inflammation and all the suffering it can cause, it can be treated and there can be a life of thriving on the other side.