Welcome to the RCCX Theory Website, Returning and New Visitors:
For those who don’t know, I am Sharon Meglathery MD, a physician (board certified in Psychiatry and previously, Internal Medicine) who developed CFS (chronic fatigue syndrome), MCAS (mast cell activation syndrome), POTS (postural orthostatic tachycardia syndrome) and raised ICP (intracranial pressure) in the setting of EDS-HT (Ehlers-Danlos Hypermobility Type). I spent 7 years trying to understand how these chronic illnesses fit together by observing my own illness, observing patients in my office, being active in online chronic illness forums, reading everything I could find and being lucky enough to have a smart friend send me a paper about the RCCX module (Martha Cassell), which explained all of my observations and the published research findings.
In July 2015, the RCCX Theory was born. I believe that the RCCX Theory solves some of medicine and psychiatry's greatest mysteries. The RCCX Theory explains the co-inheritance of a wide range of overlapping chronic medical conditions in individuals and families (EDS/hypermobility, autoimmune diseases, chronic fatiguing illness, psychiatric conditions, autism, etc.). It explains the underlying pathophysiology of chronic fatiguing illnesses with so many overlapping features (EDS-HT, CFS, Chronic Lyme Disease, Fibromyalgia, toxic mold, Epstein Barr Infection, MCAS, POTS, etc.). And finally, it reveals the gene which I believe confers a predisposition toward brilliance, gender fluidity, autistic features, and stress vulnerability, as well as the entire spectrum of psychiatric conditions (other than schizophrenia which is linked with neighboring C4 and can be co-inherited with this gene). This website contains everything you need to understand the subtleties of this theory.
In this section of the website, I will review The RCCX Theory. If the first part of this is too technical, I provide a much more simplified and detailed explanation of RCCX Theory Part I in the Part I section. Then, I will proceed to a discussion of CAPS (CYP21A2 Mutation Associated Neuropsychiatric Spectrum), the psychological profile which I believe is present in people who develop chronic illness, medical and psychiatric. If you are familiar with Parts I and II of the RCCX Theory, please feel free to skip this part (in blue).
Disclaimer: The purpose of this website is NOT to recruit patients, give treatment recommendations, sell supplements, get attention, be controversial or become famous. Please seek advice from you physician before trying anything I discuss on this website. I live a quiet, reclusive life with a small, local and full medical practice. This illness and this discovery has made my life very complicated.
RCCX Theory: Summary
Co-inherited gene mutations of the RCCX module may explain presence of clusters of genetic illness in families and individuals involving hypermobility/fibosis (TNXB gene), chronic medical illness (CYP21A2 gene, i.e. EDS-HT, CFS/ME, FM, POTS, MCAS, etc.), psychiatric illness (CYP21A2 gene) and autoimmune diseases (C4 gene).
CYP21A2 gene mutations could confer a stress vulnerability for the development of chronic medical illness (EDS-HT, CFS/ME, FM, POTS, MCAS, etc.) via "21hydroxylase overwhelm" and via PTSD-wiring from CAPS (CYP21A2 Mutation Associated Neuropsychiatric Spectrum) plus negative events.
CYP21A2 gene mutations create a hormone milieu which could affect the developing brain, making it a "brain wired for danger" by age 5, also known as CAPS (CYP21A2 Mutation Associated Psychiatric Spectrum). CAPS likely predisposes to 4/5 of the major psychiatric illnesses (anxiety disorders, mood disorders, attentional disorders, autism spectrum).
Both "21hydroxylase overwhelm" and PTSD wiring associated with CAPS could likely result in stress-induced mitochondrial shutdown (as described by Naviaux MD PhD).
To Whom Does this Theory Apply?
In many families, a cluster of the following diagnoses will be found and I believe that those families are likely to contain the gene mutations I discuss.
For example-you may see a family with a member, often female, diagnosed with or suspected to have Ehlers-Danlos Syndrome, Hypermobility Type (EDS-HT), postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS). Then in the extended family, you may find autoimmune diseases, i.e. multiple sclerosis, cutting and eating disorders, "possible bipolar disorder", gender fluidity, a highly successful and innovative genius, someone with chronic fatigue syndrome (CFS) or fibromyalgia (FM), someone with severe post-traumatic stress disorder (PTSD) and someone else with bouts of psychosis. The children who are more scrutinized in this day and age, may be diagnosed with attention deficit disorder (ADD), sensory processing issues plus or minus autistic features.
And the kicker, these issues may be found on both sides of the family because I believe that people with CAPS (the psychological profile which I believe is associated with CYP21A2 mutations) are attracted to each-other as they share sensitivities, emotional sensitivity and intellectual gifts. The degree of hypermobility ranges from none to severe in this family and correlates with the degree of musculoskeletal involvement (joint pain/dislocations/surgeries required to stabilize joints) and orthostasis/"dysautonomia," but NOT with the other "sick" symptoms which tend to develop later in life. Many will react strongly to stress.
If this sounds like your family (albeit a dramatic version), I am writing this for you.
Likely RCCX Gene Mutation-Associated Conditions Which Cluster in Individuals and Families:
Of note: These conditions can occur due to other genes, thus occurring without these clusters. Many people with MCAS and POTS, together or alone have these for a different reason. What I am writing is NOT relevant to them. (However, if you have bendy joints and MCAS and POTS, I am talking to you!)
Ehlers-Danlos Syndrome, Hypermobility Type (EDS-HT)
Misc.: Extreme Temperature Dysregulation (Dysautonomia or not), Multiple Chemical Sensitivity, High Adrenaline/Noradrenaline (also called norepinephrine) States, Erythromyalalgia, Raynaud's, Livedo Reticularis, Evidence of Poor connective tissue integrity (Dislocations, Bruising, Bleeding, Petechaie, Calcific Aortic Valves, Mitral Valve Prolapse, Abnormal Scarring, Stretch Marks, etc.), Dry eyes, Tinnitis, Subcutaneous Adipose Disorders (Lipidema, Dercum's Disease), Left Handedness, Gender Fluidity (LGTB, lack of traditional gender roles)
Perhaps: Medullary Sponge Kidney, Pyroluria, disorders of copper and zinc regulation, Early Onset Parkinson's Disease
I will refer to all of these under the rubric of "Chronic Illness" going forward.
For those of you with EDS, it is important that I clarify a few points. My theory pertains to those who have NOT been found to have a specific disease-causing collagen mutation, i.e. those who fall into the hypermobile and classical types. I will show you that I believe that we have life-long issues due to poor collagen and inflammation from TGF beta resulting from a TNXB mutation PLUS a propensity for other stress-triggered systemic issues similar to those with other chronic illnesses from an adjacent gene, CYP21A2.
I believe that the degree of hypermobility only relates to the musculoskeletal issues and that the chronic illness issues are completely separate. Thus, it is not necessary to have a diagnosis of EDS to have many of the issues most people relate to a diagnosis of EDS and associated with chronic illness.
It is impossible to test for even a fraction of the TNXB mutations associated with clinical illness and my guess is that TNXB mutations may be associated with enough hypermobility to meet criteria for EDS sometimes, but most often they are associated with only mild hypermobility or possibly even stiffness. I know that this goes against the EDS teaching/knowledge base, but keep reading and you will see why I have come to these conclusions.
What is the RCCX Module:
There is a part of the genome, nestled among the immune system genes called the RCCX module. This module breaks the rules of genetics in that it mutates often (even between generations) and it allows contiguous (side-by-side) gene mutations to be co-inherited at a very high rate, meaning that it allows for several “rare” genetic conditions to be found in one individual.
There are 4 genes in the RCCX moduleand their mutations have been shown to travel together often within individuals and families:
RP1: function unknown
TNXB: codes for tenascin X, a protein found in the extracellular matrix of collagen
Mutations sometimes associated withEDS
Mutations often associated with joint hypermobility NOT meeting criteria for EDS
Mutations possibly associated with stiff or even normal-seeming tissues depending on the mutation,
Mutations have been associated with TGF beta abnormalities implicated in fibrosis
C4 :codes for a protein involved in the complement system of the immune system
Mutations implicated in autoimmune diseases, immunodeficiency/CVID, schizophrenia
CYP21A2: codes for the key enzyme, 21hydroxylase, which is involved in the acute stress response. 21hydroxylase helps to make cortisol from 17 hydroxyprogesterone and aldosterone.
Mutations result in an exaggerated stress response (high acute stress response cortisol), low basal cortisol and elevatedCRH (corticotropin releasing hormone, aka CRF) which directly turns on the immune system and inflammation.
Mutations are also associated with autosomal recessivecongenital adrenal hyperplasia (CAH), usually diagnosed in infancy due to its association with extreme salt wasting (due to low aldosterone) and dangerously low cortisol. A milder form, non-classical CAH, presents later in life.
It is highly likely that there are MANY uncharacterized (mild) mutationswhich, in homozygous or even heterozygous forms, would cause a wide range of clinical presentations.
Carriers of CYP21A2 mutations have BOTH an exaggerated stress response ANDare at risk for 21 hydroxylase failure resulting in inability to make cortisol and aldosterone with subsequent 17 hydroxyprogesterone and androgen build up. Called "21hydroxylase overwhelm" going forward. This is a stress-vulnerable switch which can result in severe chronic illness if flipped.
I believe that "21hydroxylase overwhelm" is the basis for many aspects of chronic illness as theoretically, this can be causally linked with many of the syndromes associated with chronic illness, including: MCAS, POTS, immune dysfunction, etc. (See Pathophysiology Diagram below). For more information about this, please see RCCX Theory Part I.
Additionally, I believe that the presence of this mutation can lead to a distinct psychiatric profile, CAPS (CYP21A2 Mutation Associated Neuropsychiatric Profile, discussed below), brain structural and wiring abnormalities, and sometimes psychiatric illness (ADD, Anxiety, PTSD, Mood disorders, autism, and even psychosis if brain inflammation often associated with MCAS).
The RCCX Module is Responsible For Co-Segregating Genetic Diseases and Syndromes in Individuals and Families
Evidence is mounting that mutations of RCCX genes are extremely common in the general population (e.g. CYP21A2 mutations are likely present in about 20% of the population) and exert significant health effects.Most of the SNPs associated with mutations in these genes have not been characterized as they mutate so often. Further, there are so many insertions in this region that it is often difficult even to identify SNPs at all. Occasionally, genetic testing will reveal a SNP but the clinical significance is never clear as they have not yet been characterized. This is why we can’t use 23andme or whole exome sequencing yet to reliably find all of these mutations.
The genetics literature continues to provide more and more examples of overlapping clinical pictures caused by mutations of these genes travelling together. The recognition of this is in its infancy, but by most indications, should be quite prevalent.
These overlapping syndromes would be expected to run together in families and in individuals, resulting in multiple “rare” conditions being present in one individual or throughout a family (see specific list of conditions). We would see elements of the following conditions running through families:
Autoimmune diseases, immunodeficiency disorders, like CVID, schizophrenia, autism (C4)
Characteristics of CAH (CYP21A2) which include adrenal and sex hormone abnormalities (low basal cortisol with high acute stress cortisol, sex hormone abnormalities dependent on clinical status), gender fluidity, and as I have posited, brain structural and circuit abnormalities (CAPS psychological profile, wiring for danger, special abilities-see below), chronic illness: psychiatric (ADD, Anxiety, Mood, Autism) and medical (CFS/ME/Lyme/FM/immune dysfunction via CRH/MCAS/POTS etc.)
This is exactly what is seen in real life. Families containing geniuses, people with CFS/ME/Lyme/FM, hypermobile folks, gay/transgender people, people with autoimmune diseases, people with endometriosis, people with subcutaneous adipose disorders, etc, etc. See the full list above.
CYP21A2 Mutations Likely Underlie Chronic Illness
As stated above, The RCCX Theory posits that severe acute stress (e.g. toxic mold exposure, Borrelia Bugdorferi infection, physical or emotional trauma, etc.) or prolonged stress can set in motion severe chronic illness in a stress-vulnerable person (a CYP21A2 mutation carrier with perhaps additional other specific susceptibility genes specific for the inciting infectious or toxic agent, making it a particularly strong stressor). The CYP21A2 mutation contains an evolutionary switch which is flipped as the person desperately tries to make enough cortisol to handle the stress, triggering 21 hydroxylase overwhelm and then possibly stress-induced mitochondrial shutdown. This mitochondrial shutdown has very recently been discovered in patients with severe CFS/ME by Ron Davis PhD and Robert Naviaux MD PhD. The symptoms which occur after 21 hydroxylase is overwhelmed are the same, independent of the trigger. For more information about this, please see RCCX Theory Part I.
There are still many people who believe that these chronic illness conditions are completely separate in pathophysiology, e.g. all of the symptoms associated with EDS are solely caused by a genetic defect of collagen, all of the symptoms of Lyme disease are caused by Borrelia Bugdorferi, all symptoms of CERS are caused by the inciting agent, etc.
But, everyday, it is becoming more clear that these conditions all go down a common pathway. There are just too many very specific overlapping symptoms for it to be any other way. The RCCX Theory unites all of the findings:
White Matter Lesions (CAH, EDS, CFS/ME, MS, Lyme, etc.)
Erythromelalgia/Small Fiber Polyneuropathy (EDS, FM, Gulf War Veterans, CFS/ME etc.)
Autonomic Nervous System Dysfunction/POTS/Orthostatic Intolerance (all)
Association with Autoimmune Diseases (All, anecdotally)
High Adrenaline/Exaggerated Acute Stress Response (EDS, CFS/ME, CYP21A2 carriers)
Treating MCAS, correcting MTHFR, LDN, maintaining adequate hydration/salt repletion, correcting dysbiosis, anti-inflammatories, mitochondrial support, diamox, immune system agents, mindfulness/grounding/brain retraining and stress reduction are overlapping treatments which seem to help these conditions.
For me, the most compelling piece of evidence that all of these conditions have a common mechanism is the psychological profile, CAPS, I have discovered which is universally present and allows for the prediction of who is at risk for developing chronic illness. See the Background section to read about the discovery of CAPS and its associations. CAPS is very often associated with hypermobility but not always. Thus, it makes sense that it would be associated with a gene which runs with hypermobility (TNXB) but is a separate gene (CYP21A2). The hormone milieu one would expect with the CYP21A2 mutation explains the findings in the CAPS, a "brain wired for danger" as this milieu is very similar to what would be seen in a child experiencing very adverse circumstances/trauma. It's fascinating that white matter lesions have been found in patients with CAH, 2 copies of a known CYP21A2 mutation.
More of these overlapping symptoms can be found on the forums, as some of this has not yet made it into the literature. Further, it is also becoming increasingly clear that the above RCCX co-morbidities run with these conditions in individuals and within families.
Additionally, the RCCX Theory may also end up explaining some of the other off-center theories of chronic illness, such as the role of pyroles in chronic illness (21 hydroxylase contains heme moiety. It is possible that heme moieties could rise to high levels if the body was trying unsuccessfully to make 21 hydroxylase in an attempt to raise cortisol to appropriate stress levels). Also, the idea that 20% of the population is at risk for MCAS at times of stress (those with CYP21A2 mutations) jibes with orthomolecular psychiatry’s claim of histamine being a major player in psychiatric illness (I believe that it's actually MCAS which is histamine PLUS other mediators).
There is no evidence that I have found anywhere which contradicts the RCCX Theory and I have read everything I can find! As long as specialists continue to say that any co-morbidity overlap is due to chance alone, we will never move forward.
I believe that Ron Davis PhD (a premier CFS/ME researcher) sees this as well, as he has included people with EDS in his CFS/ME studies.
From RCCX Theory to Cell Danger Response (Added to RCCX Theory in July 2016): In June 2016, Ron Davis, PhD and Robert Naviaux, MD PhD demonstrated that stress-induced mitochondrial shutdown occurs in severely ill CFS/ME patients in a pilot study. This mitochondrial shutdown is believed to be a normal, possibly temporary physiological response to stress which seems to be prolonged in CFS/ME, perhaps due to maintaining forces. I suspect that these findings are relevant to all of the chronically ill people mentioned in the previous section, as the RCCX Theory proposes a shared stress vulnerability mediated by CYP21A2 mutations. As stated above, I believe that this stress vulnerability unites many groups of people with chronic illness, some hypermobile and some not, (see above) and thus, mitochondrial shutdown is likely to be a relevant process to all.
PTSD is a known risk factor for turning on this mitochondrial shutdown, as is a variety of toxic external and internal stressors, according to Naviaux MD PhD who initially discovered and described this process.
I believe that CAPS, which I believe is due to spiking cortisol levels in the setting of low basal cortisol during gestation and infancy from the presence of one or more CYP21A2 mutations, may be one of the most common risk factors for the development of PTSD. (See below for details.)
Mitochondrial shutdown has also been found in autism which I have linked to CAPS.
I also believe that there are several other ways that RCCX mutations can cause mitochondrial shutdown by increasing the body’s stress load:
TNXB (codes for tenascin X, a protein involved with collagen) mutations are associated with TGF beta abnormalities (fibrosis, inflammation, etc) and lax blood vessels (orthostasis), i.e. inflammatory and cardiovascular stress.
C4 mutations are associated with schizophrenia, autoimmune diseases and immunodeficiencyconditions (MS, CVID, etc.), adding to inflammatory, immunological and psychiatric stress.
CYP21A2 mutations are associated with BOTH an exaggerated stress responseAND the possibility of overwhelming 21 hydoxylase, the enzyme making cortisol and aldosterone from progesterone. Mast cell activation syndrome (MCAS) and the immune system can turn on in response to elevated CRH (corticotropin releasing hormone) due to low basal cortisol, resulting in a variety of derangements in hormone levels, immune responses, inflammation and clinical syndromes (see above pathophysiology diagram, RCCX Theory Part I). This increases the stress load by adding hormonal, immunological, inflammatory, psychiatric (anxiety) and cardiovascular stress.
As mentioned above, the exaggerated response to stress (spiking cortisol) in infants with CYP21A2 mutations may also result in a brain wired for danger (CAPS) which is stress vulnerable, associated with dysautonomia and emotional dysregulation. With negative events, the exaggerated acute stress response (and perhaps epigenetic effects-see below) could facilitate the development of severe, PTSD-like brain wiring which worsens the dysautonomia and emotional dysregulation, further increasing the acute stress response. This can result in distressing dissociative (dysautonomic, sensory, motor) syndromes via brainstem/limbic system circuits as well as other psychiatric illnesses (predisposes to 4 of the major psychiatric illnesses: ADD, Anxiety Disorders, Mood Disorders, autistic features). Brain inflammation from MCAS/CRH can complicate the picture, as can the addition of C4 mutations can result in schizophrenia or possibly more severe autistic features. (I have observed all of this clinically). This increases the stress load by adding cardiovascular and psychiatric stress.
Based on my observations and the evidence demonstrating that features of RCCX mutations are highly present in the chronically ill population (see the rest of the website), I believe that the RCCX mutations are responsible for creating the level of toxic stress necessary to shut down the mitochondria indefinitely in a high percentage of people with chronic illness.
But why would we have genes which predispose us to chronic illness?
The RCCX Module Is Designed to Adapt to Changing Environments; C4 and CYP21A2 Confer the Ability to Cope with New Pathogens and Changing Levels of Environmental Stress
Evolutionarily, our immune system is designed to battle frequently mutating pathogens by having the capability of generating extremely varied components due to highly mutable genes. Most of these genes are within the MHC class III region of the genome. The RCCX module sits in this region, even though C4 is the only known immune system gene in the RCCX module. The C4 gene is able to produce a highly diverse complement protein gene product, also called C4, which is able to adapt exceptionally well to new threats through frequent and varied mutations. C4 is also very much involved in neurodevelopment by controlling the process of dendritic pruning, altering the communication between neurons.
At first glance, it is unclear why CYP21A2, coding for the major enzyme in the acute stress response, would be located in such a mutation-prone part of the genome. The literature suggests that it just happens to be there, but I believe that this is part of a very clever plan to allow for adaptation to changing levels of stress from generation to generation and throughout the lifespan of the person.
If a child is born into a highly stressful environment, then the exaggerated stress response known to be associated with CYP21A2 mutations would confer superior threat recognition and a more rapid response, both of which are clearly vital to survival in a dangerous environment. Further, it is highly likely that CYP21A2 mutations can, via epigenetic changes, adapt to changing levels of stress throughout the lifespan, allowing the person to thrive in an ever-changing environment. ("Epigenetic" gene changes refer to modifications in the gene after birth which affect its expression.) In the last several years, transgenerational epigenetic changes have been observed in other stress-affected genes, allowing stress-induced, presumably adaptive, genetic changes conferred on one generation to be passed on to at least several later generations. It stands to reason that this could happen with the CYP21A2 gene as well, making it a very important gene for survival.
While mutations and epigenetic changes are thought of as facilitating adaptation to hardship, it is highly likely that they can also bring about the removal of genes which are no longer advantageous.
What if the inherited CYP21A2 mutation is associated with a drastically high stress response for the current environment, as could possibly happen by chance or if transgenerational epigenetic effects occurred during a very stressful time several generations back?
This excessively high stress response would have no survival advantage and thus evolutionarily speaking, this CYP21A2 mutation should probably be removed from the gene pool.
And what about if the environmental danger/threat level becomes so high that a sensitive CAPS person is hypervigilant and jacked up at all times, unable to sleep ever?
From an evolutionary standpoint, it is not advantageous for this person to bring similarly wired children into this environment or to continue tolerating it as it is. Again, evolutionarily, there is a mismatch between the person and the environment and the mutated CYP21A2 should be removed from the gene pool.
(I bold the word "evolutionarily" to show that this is about natural selection and not about my personal preferences :))
I believe that CYP21A2 mutations may be programmed to be removed from the gene pool by two different built-in physiological mechanisms. The first, 21hydroxylase overwhelm may, initially, prevent procreation and with continuing stress, cause mitochondrial shut down, if the stress to stress response mismatch becomes excessive. The second physiological mechanism involves the CAPS brain transforming into severe psychiatric illness due to dissociative limbic (emotional) and brainstem (autonomic. motor and sensory) circuits, brain inflammation from MCAS and other downstream effects of CRH.
Regarding the first mechanism, 21hydroxylase overwhelm, it is necessary to remember that CYP21A2 mutations result in a vigorous acute stress response requiring high amounts of cortisol AND ironically, they also cause a decreased ability to produce functional 21hydroxylase, the enzyme which produces cortisol. At first this seems counter-intuitive, but it's a very clever way to build in a vulnerability to situations requiring excessive amounts of cortisol, i.e. a switch to turn on a cascade of events which could lead to removal of the gene from the gene pool. The switch gets flipped when the person is carrying a mutation with an inappropriately exaggerated stress response for the environment at hand or if a CAPS person is exposed to a very toxic/prolonged stressor or a very stressful/dangerous environment without escape. These situations result in an acute stress response which is woefully inappropriate, being turned on continually and never able to calm down.
These stress:stress response mismatch situations lead to an inadequate amount of 21hydroxylase being produced for the situation. In both cases, cortisol is being consumed at a tremendous rate. In the first case, it is being consumed for no reason other than an inappropriate gene mutation and in the second, something really toxic is happening. With this high cortisol demand, 21hydroxylase becomes overwhelmed and cortisol and aldosterone drop, decreasing the ability to respond to stress. CRH rises, turning on inflammatory pathways (MCAS, etc.), changing the immune system (immunodeficiency, dysbiosis) and sometimes, causing psychosis from brain inflammation. Additionally, there are major changes in sex hormone levels. Metabolic syndrome sets in from elevated cholesterol and dysbiosis. Malabsorption wipes out necessary vitamin stores. Without drasticchanges in either the environment or the response to the environment, the fall-out from the flipped 21hydroxylase switch leads to chronic illness plus or minus mitochondrial shutdown.
As these hormonal, metabolic and inflammatory changes are additive in terms of stress load, it is probably very difficult to reset either the 21hydroxylase switch or the mitochondrial switch once they are flipped in someone with a CYP21A2 mutation. The person succumbs to this toxic stress, in stages, first unable to procreate from the hormonal changes (high progesterone, high testosterone in women cause early menopause) and then unable to muster the energy to move due to the mitochondrial shutdown. In nature, mitochondrial shutdown for any length of time would lead to certain death. In modern human society, it leads to a dwindling existence.
The second way for CYP21A2 mutations to shut down the mitochondria is via PTSD-like brain circuits. Maladaptive, epigenetic and catecholamine-induced changes in brain circuitry in response to traumatic events is becoming better understood every day. To my knowledge, no one has brought up the potential magnifying effects that CYP21A2 mutations may exert on this process by ramping up arousal and catecholamines even during mild negative events. It stands to reason that the CAPS brain is extremely vulnerable to PTSD wiring and this is what I see clinically and in myself. This PTSD wiring increases vulnerability to other psychiatric disorders and in turn, ramps up the acute stress response even further (via new triggers, dysautonomic brainstem and limbic circuits), greatly increasing the demand for cortisol and easily flipping the 21hydroxylase switch, potentially leading to mitochondrial shutdown as discussed above. Additionally. CYP21A2 mutation-associated PTSD wiring, and other psychiatric stress likely also lead directly to mitochondrial shutdown. Again mitochondrial hypometabolism is maintained by the high stress load and again, the maladaptive gene is effectively removed from the gene pool.
This latter mechanism would explain the results of the CDC Kaiser ACE study of 17,000 patients showing that early childhood adversity is correlated in a dose response manner with significant negative health effects, including headaches, mental illness (depression, psychosis, suicide attempts) and autoimmune/inflammatory diseases, with some people more vulnerable than others. I believe that the vulnerable ones are carrying CYP21A2 mutations.
As described in the Background section of this website, I have found a psychological profile which I believe is associated with CYP21A2 mutations, dubbed CAPS (now short for CYP21A2 Associated Neuropsychiatric Spectrum), which seems to be a strong marker for risk of developing chronic psychiatric and medical illness. I know it seems extraordinary that this has been missed, but the questions to recognize CAPS in patients are not the questions typically asked in a busy medication management psychiatric practice. I came across CAPS in 2009 when I started checking everyone (patients and friends) for hypermobility and with this, I began to notice distinct psychological characteristics, usually, but not always associated with hypermobility.
Typically, my patients come to my practice to change how they handle life, so I spend quite a bit of time looking at how they view themselves, their lives, and their worlds. People with CAPS stand out when viewed from this vantage point, especially when one sees that this way of being tends to sort with joint hypermobility. While CAPS is not pathological in itself, I have come to find that the stress vulnerability and increased risk of brain inflammation (MCAS, possibly elevated CRH) in this population predisposes to the development of psychiatric illness in some cases (see the secondary CAPS below). It is important for me to say here that I am quite sure that there are many people with CAPS who don't ever see the inside of a psychiatrist's office.
I myself have CAPS and prior to becoming sick, I was gutsy, extroverted, adventurous (back-packed around Africa and Asia alone), creative, smart and outspoken, although I was a worrier ('brain wired for danger"). After becoming sick, I became introverted, cautious, physically anxious and haunted by the past. This is a trajectory I have seen many times with CAPS and it is just one way it can go. By the end of this section, you will understand...
CAPS contains many of the same elements as the Highly Sensitive Person profile of sensory perception sensitivity (SPS) developed and studied by Elain Aron PhD. As I have learned the implications of the gene behind it and its clinical associations with chronic medical and psychiatric illness, I have been able to reveal more aspects of it.
Unfortunately, CAPS has been missed by the researchers studying psychological characteristics associated with chronic illness because of false assumptions including:
Emotional and sensory sensitivities are a result of having a chronic illness.
The odious idea that we must be amplifying our symptoms because no one can be that sick with a negative medical work-up.
Additionally, backlash from the chronically ill population which, until recently, had been subjugated to cognitive behavioral therapy to "correct dysfunctional beliefs about being ill" has resulted in strongly discouraging further research into this area. I was skewered on a popular CFS/ME forum for the RCCX Theory even though it posits that we are, in fact, deathly ill from hormonal and inflammatory cascades. At issue was the idea that stress may be turning on these cascades and that we may be stress vulnerable.
Because the hypermobile folks have been kept in a diagnostically separate group, their unique psychological profile has been noticed by psychiatry. They have been found to be very much at increased risk for all sorts of chronic psychiatric and medical illness. In fact, a very large study published July 4, 2016 (Cederlof) involving the Swedish registry (1780 EDS, 1722 siblings of EDS patients, 10019 with hypermobility syndrome and 11082 hypermobility siblings) showed a substantially higher risk for autism spectrum, bipolar disorder, ADHD and depression in EDS patients, hypermobility syndrome patients and their non-affected siblings. Additionally, other studies have revealed a high rate of obsessive compulsive personality disorder, anxiety disorders/panic and phobias. Hypermobiles have been said to have a neuro-visceral phenotype (constitutional differences in control of bodily state, Eccles) and a spectrum disorder called ALPIM (anxiety, pain, ligament laxity, inflammation). All of this has been discovered/published while I was carefully working through the characteristics of CAPS.
Over time, I realized that while all of the people presenting to my psychiatric practice with hypermobility had CAPS, I noted that CAPS was also present in a few people who are not hypermobile. Interestingly, several people with CAPS developed chronic medical and psychiatric illnesses right in front of me, convincing me that this psychological profile is closer to the origin of illness than hypermobility.
For years, I observed people with CAPS, trying to distill the essence of it. When I learned about the frequent co-inheritance of the RCCX Module genes, it was obvious to me that the hypermobility gene, TNXB, is not the important gene in CAPS or chronic illness. Rather, it is very clear to me that CYP21A2 mutations are responsible for both CAPS and chronic illness, whether or not they have the often accompanying TNXB mutation (which brings with it the complications of musculoskeletal/structural issues and TGF beta). Going back to the Swedish study mentioned above, the presence of a high rate of identical psychiatric disorders in EDS patients, joint hypermobility syndrome patients and in unaffected siblings validates what I have been seeing and claiming all of this time, the psych issues are rampant and NOT dependent on the presence or degree of hypermobility, but rather the presence of hypermobilityin the family is all that matters. The RCCX Theory makes sense of this observation: CYP21A2 mutations are responsible for the psychiatric issues, with TNXB co-inheritance occurring commonly but not every time.
As mentioned above and discussed in detail in the Background section, I have observed that CAPS predicts development of significant chronic psychiatric and medical illness. In fact, over the 7 years that I have been watching this connection, I have watched many hypermobiles and non-hypermobiles with CAPS develop one or both of these right in front of me, usually with evidence of hormone disruption and/or mast cell activation at the same time. I have also treated people with specific exposures believed to have triggered their chronic illness (exposure to Borrelia Bugdorferi, exposure to toxic mold) and they also have CAPS.
When I learned about the RCCX module and the fact that CYP21A2 and TNXB are frequently co-inherited, it was obvious to me that there could be no other explanation for CAPS but exposure abnormal levels of stress hormones and androgens during critical periods of brain development, as would happen in the presence of CYP21A2 mutations. Further, the frequent presence of hypermobility and autoimmune diseases in patients and their families was also explained by this revelation, as were the physical findings suggestive of high androgens during development and other hormone issues throughout life (reviewed in the Journal Article).
It is in the literature that males with untreated congenital adrenal hyperplasia (CAH, 2 copies of known CYP21A2 mutations), who presumably have the same hormone milieu affecting their developing brains as people who developing CAPS, have a very high rate of psychiatric illness compared to normals AND compared to those who are treated with steroids at birth, which reverses the hormone abnormalities before they can affect brain development in infancy. Further, white matter lesions of unclear etiology are often found in the brains of patients with CAH, mirroring, the lesions found in people with EDS, Lyme, CFS/ME etc. Too many coincidences for CAPS not to result from CYP21A2 mutations.
Before I discuss the clinical features of CAPS, I think it is important to discuss specifically how it would develop based on the idea that CYP21A2 mutations underlie its development.
CYP21A2 Mutations May Lead to CAPS, PTSD Circuits: Brainstem Motor, Sensory and Autonomic Nervous System Derangements, Limbic Excitability and Psychiatric Illness
The knowledge of the hormonal alterations associated with CYP21A2 mutations, allows for a deeper understanding of this profile: Low basal cortisol in gestation and infancy and spiking stress response cortisol starting in infancy with variably high androgens thoughout.
The hormone abnormalities associated with congenital adrenal hyperplasia, CAH, (2 mutated copies of the CYP21A2 gene) are known to affect the development of the hippocampus and amygdala. The amygdala, the emotional/fear center, is rich with androgen and cortisol receptors and is known to increase in size after birth as a result of exposure to stress and androgen stimulation. People born with CYP21A2 mutations are born with small amygdalae due to low basal cortisol in utero (with minimal stress spiking) and those who are treated at birth with a steady dose of physiological hydrocortisone at birth (with subsequent lowering of androgens and prevention of the spiking acute stress response cortisol) have also been found to have smaller than normal amygdalae as children (measured via MRI). Those with CYP21A2 mutations which are unrecognized, and thus untreated would have spiking cortisol in response to stress after birth and high androgens in the background of low basal cortisol, stimulating the growth of the amygdala in the postnatal period. This is what is seen in some of the populations (EDS, autism, toxic mold) which I associate with CAPS and to my knowledge the amydalae have not been measured in the other populations.
A review by Delude (http://protomag.com/articles/scars-that-dont-fade) goes over some of the major studies looking at brain development/wiring in traumatized children, including the enlarged amygdalae, epigenetic changes altering neural circuitry by promoting a primed a danger response in traumatized children and the propensity for the development of PTSD with its association with chronic medical, inflammatory and psychiatric illness (ACE Study). She also covers the stress-induced epigenetic changes in glucocorticoid receptors and brain plasticity which are most dramatic in people who have experienced childhood traumatization contributing to PTSD symptoms. I believe that all of these processes are at work in the people with CYP21A2 mutations regardless of degree of trauma due to increased catecholamines during the frequent and exaggerated acute stress responses and the subsequent reinforcement of threat circuits with even mildly aversive life events.
Specifically, it makes sense that the brain produced at the end of infancy (around 5 years old) in children with CYP21A2 mutations would very much resemble the brain produced in children exposed to extreme stress during these crucial developmental periods due to the similar hormone milieu, minus the androgen effects. As mentioned above, high androgens and spiking cortisol could direct postpartum brain development toward an enlarged amygdala, smaller anterior cingulate and enhanced brain-stem danger responses. An enlarged amygdala (as demonstrated in hypermobile folks) would result in strong emotional and fear responses without the benefit of a strong anterior cingulate to provide balance. Further, the spiking cortisol could explain further alterations in brain circuitry, wiring the brain for danger, resulting in similarities with mild PTSD physiology by the age of 5 with minimal trauma. This would include:
mild dysautonomia: low parasympathetic nervous system (rest and digest) tone, high sympathetic nervous system (fight or flight) tone, but intrusive autonomic dissociative circuits could also occur-see below
possible brain-stem dissociative reactions including:
motor responses like orienting, catatonia, dystonia, tremor
sensory signs like pain, numbness, hallucinations
autonomic responses like fight, flight, freeze and submission
a tendency for emergent episodes of emotional dysregulation (numbing/shutdown, melt-downs).
With this brain wired for threat detection and hyper-vigilance, life stress and negative experiences later in life would trigger the stress-induced epigenetic brain changes, further enhancing these PTSD characteristics (now with frank flashbacks, nightmares, worsening dysautonomia, now frequent dissociated brainstem-derived reflexes/neurological actions and limbic-derived emotional states), pushing the person down the path toward 21hydroxylase overwhelm and prolonged CDR.
This is EXACTLY what I see clinically in people with CAPS before they get sick. This is also what is seen in hypermobiles, coming to see a psychiatrist, before they get sick.
(Of note, submission/shutdown has been associated intermittent opioid dumping. Opioids have been associated with mast cell activation and brain microglial inflammation. Their release due to wired-in brain stem stress responses could provide an explanation for the atypical response to opiates in people with EDS (less responsive anecdotally) and perhaps some of the favorable response to low dose naltrexone (LDN) in terms of both chronic illness inflammation and PTSD-associated dissociative symptoms and inflammation.)
Clinical Features of CAPS
With this knowledge, I was able to divide the symptoms I observe in CAPS into 2 groups: primary and secondary.
Primary symptoms are due to this wiring alone.
Secondary symptoms occur in people with CAPS in the following circumstances:
if the presumed mutation produced an especially high acute stress response
with exposure to adverse events
in the setting of 21hydroxylase overwhelm with brain inflammation.
Again, primary CAPS characteristics are not pathological and probably occur in about 20% of the population which correlates with Elaine Aron's estimate for the prevalence of HSP. As people with CYP21A2 mutations are "wired for danger", I believe that they can perform exceptionally well within a certain range of danger, depending on the exact nature of the individual mutation, i.e. how exaggerated the acute stress response is. In emergency situations, many people with CAPS are energized by their adrenaline and can focus on what needs to be done in the moment, while "normal" people are oblivious to threats and they lack the adrenaline dumping and laser-sharp focus of CAPS which can confer a survival advantage. It is quite difficult to sneak up on someone with CAPS, unless he/she is engrossed in something else. People with CAPS may enjoy and excel in daring activities, and they can even become addicted to the adrenaline rush associated with these activities, as long as they are in control of the situation, calling all of the shots.
In my experience with people with primary CAPS who present with psychiatric concernsI find:
Anxiety/high arousal during times of stress (evidence of high adrenaline) with resulting insomnia, sometimes manic-like characteristics, “tired and wired”, “turbo” (hyperfocus/adrenaline/acute stress response/orienting response)
Extreme hyperfocus, can get into "flow" and even forget to urinate (children will wet self sometimes)
Evidence of increased sympathetic nervous system tone and blood pooling (if hypermobile): dilated pupils, increased startle, livedo reticularis, bluish toes, sitting with legs wrapped around each-other, complaints of temperature dysregulation, hunched over, rocking and fidgeting
Under-arousal during times of low stress (often leading diagnosis of ADD) usually associated with behaviors to modify this state: compulsive (sometimes addictive) behaviors like eating, substance abuse and sometimes, thrill-seeking behaviors, etc. to increase arousal
High sensitivity/reactivity/emotionality often associated with intruding environmental stimuli when trying to hyper-focus or sleep, sensory processing disorders which present with over-stimulation in places with an excess of noise, stimulation. Of note, can be elated in high stimuli environments, if still finding the excess adrenaline to be a “fun rush”
A remarkable ability to read emotions in others (which can be overwhelming for some), but often social awkwardness and inappropriateness in response ("mind-blindness"-thinking others know how they are feeling and assuming others see the world the way they do.) Difficulty with social rhythms, eye contact, speaking in turn. Very upset by interpersonal cruelty.
Can be easily traumatized by "small" events (horror movie or off-hand comment by another person for example) once the adrenaline is no longer thrilling
Easily distracted when not hyper-focused, shiny object syndrome (sometimes meets criteria for ADD), hyper-vigilant
A tendency toward non-conformity due to different priorities than others
Special abilities (the type varies-but often includes very gifted musicians, scientists, etc...) due to highly developed circuits not found in others, coupled with hyper-focus and obsession with certain areas of interest (orienting response), often leading to remarkable accomplishments.
Exceptionally good at processing large amounts of information and reaching conclusions, picking out patterns, seeing small details others miss
A fascination with systems, understanding "why"
Sense of urgency tends to increase goal-directed behaviors, cutting down on "small talk"
People with CYP21A2 mutations have different exposure to sex hormones than other people and effects consistent with this can be seen in people with CAPS. My male patients express that they relate very well to women due to having the same communication style and often, viewpoints. The women almost across the board are noted to have signs of intrauterine androgen exposure (in terms of having longer ring fingers when compared to index fingers, a finding associated with congenital adrenal hyperplasia and high powered careers). They are often very competitive, outspoken and many choose less traditional work and social roles. Some identify as gay, bisexual or transgender. Anecdotally, most of the LGTB people I have met have CAPS.
People with CAPS can be highly successful due to their sense of vision, determination, abilities and tenacity. It is no coincidence that if you dig, you will see that hypermobility and chronic illness surrounds people with amazing accomplishments and abilities-geniuses, celebrities, mavericks.
“Autistic Features” Associated with Primary CAPS
Over the past several years, it has come to light that there is a high prevalence of autism in the families of people with MCAS, EDS and other chronic illnesses. Autism has been associated with bigger than normal amygdalae, androgenization of the brain, a high rate of PTSD and chronic illness (dysbiosis, MCAS, mitochondrial shutdown, brain inflammation, etc.). Further, autism has been associated with the same neuro-visceral sensitivities which are found in people with hypermobile EDS (Eccles). I have been noting this association with autism in the EDS population for years (before it was in the literature), and the autistic features are certainly part of the CAPS profile (danger response, PTSD, sensory issues, special abilities, tenacity, special interests, systems approach, unconventionality, social awkwardness, attentional issues).
But there is one thing that doesn’t quite fit with what is classically described as autism. People with CAPS are empaths. In keeping with this, people with EDS have been found to respond very strongly to emotional expressions in others via functional MRI. Further, the HSP profile is supposed to be the opposite of autism. Psychiatric/psychological scales testing for autism, like the ASQ, lower your score if you are empathic. When I was trying to figure out what could be driving CAPS, I wondered if the mental health field had been misinterpreting autism all along-could people with autism be so sensitive to the emotions of others that they shut down and withdraw, appearing not to care to interact at all, when in fact, they are desperately wanting to connect socially? I believe that this is true of most of the CAPS variety.
However, there are clearly autistic people who claim that they don’t feel/understand romantic love and are very much flummoxed by emotional reactions in others, as Temple Grandin describes herself to be. Several possible explanations for this disparity present themselves. I believe that this might represent a different flavor of autism, either not related to CYP21A2 mutations at all or perhaps, these people have co-segregating C4 mutations with associated abnormalities in dendritic branching. (Autism has been linked with the C4 gene). In the previous versions of this website, I drew attention to my earlier idea that low level brain MCAS triggered by elevated CRH (due to low basal cortisol in people with the CYP21A2 mutation) could result in the so-called autistic features associated with CAPS. This was based on Dr. Theoharides’ work demonstrating a link between MCAS and autism, and the fact that some autistic features seem to get much worse when central (brain) MCAS is present. Variable amounts of MCAS present during infancy could possibly contribute to autistic wiring which is more associated with this lack of empathy. It is also possible that significant early trauma could completely shut down the interpersonal connection branch of the vagus nerve, as described in Porges’ Polyvagal Theory, in people who would normally be empaths due to CYP21A2-directed brain wiring. If this happened early enough, neuroplasticity could result in loss of the empathic wiring, perhaps.
Interestingly, John Elder Robison, an author with autism and a self-described lack of empathy, speaks of the fall-out he experienced when he underwent transcranial magnetic stimulation as part of a research project and had all of his empathic connections suddenly turned on. This would argue that these connections are present in the brain but are shut down for some apparent reason (PTSD shutdown would be a good explanation).
I am not the only mental health professional to be perplexed by the finding of very high empathy in people with autistic features. A fascinating recent article in Scientific American (Rebecca Brewer) discusses this finding and studies looking at the differences between autistic people with and without empathy. What they found was that those who seem to lack empathy are actually alexithymic (not able to recognize and name their own emotions), rather than lacking empathy per se. I believe that extreme mind-blindness (difficulty distinguishing one's viewpoints from those of others) may play a role in this as well.
Looking more closely at the "autistic features" associated with CAPS, we can see that the sensory sensitivity issues may actually be part of a wired-in orienting response. If you are in danger, it is very important to direct your attention to any sensation which falls outside of the expected. The detection of any slight odor, any sound separate from background noise, any detected movement slightly different from the wind could have great survival benefit. Further, when other distracting sensory inputs occur when one is using his/her “spidy” senses, it makes sense that there is great emotional distress/overwhelm.
Special abilities in people with CAPS often involve the ability to process large amounts of information, the ability to access and integrate parts of the brain to a higher degree than others and sometimes even a photographic memory. These are just the sort of abilities which would also improve survival in a dangerous world where any delay or error in processing separates life from death. With a heightened sense of urgency to complete tasks/solve problems/ make things OK/safe again comes the “turbo” to sift through and assimilate information (see my story with “turbo” in the Background Section-in blue) and the tenacity/obsessiveness/special interests to make sure it is done completely and well. The strong systems approach to problems may come from trying to make sense of world because by figuring it out, you might make it safer. That’s why the CAPS folks always want to know “why?”
The unconventionality/social awkwardness could be due to a greater emphasis on threat assessment/action rather than fitting in or being social (different priorities as set up by the brain). This is in line with Porges’ polyvagal theory which posits that the social/connection branch of the vagus nerve is completely shut down in the presence of threat. The empath qualities in CAPS are present because they assist in threat assessment as well. Statistically, I have been very “lucky” during the years I worked as an emergency room psychiatrist, in that I was never assaulted. I believe that I owe this to CAPS. To me it makes perfect sense that the empath/wired for danger/neurovisceral/dysautonomia flavor of autism has an underlying CYP21A2 mutation laying the ground work. It also makes sense that MCAS may alter or stimulate some of this wiring during active brain inflammation, and that as the person becomes more stressed in the setting of chronic illness, there is decreased social engagement/connection constriction due to worsening PTSD circuitry (decreased oxytocin, shutting down of the ventral vagus nerve per Porges), making the autism look "worse".
Sexual Flavor Sometimes Associated with Primary CAPS
As discussed above, I believe that many features of CAPS likely result from the presence of low basal cortisol during gestation and spiking acute stress cortisol in infancy, but what about the influence of abnormal sex hormone levels on brain development? The answer would perhaps come from examining people with known CYP21A2 mutations who do not receive cortisol in infancy (treating with cortisol would decrease the androgen exposure and change the cortisol-influenced brain changes during this time of rapid brain development).
Unfortunately, most of the studies regarding the brain and neuropsychiatric/psychological aspects of CAH have been done on people with classical CAH (most likely treated with cortisol) or mixed populations. These have revealed that CAH girls have superior spatial abilities and have personalities less embracing of traditional sex roles: less doll play, more aggressive, tomboyish, not as much interest in child rearing with male pattern of distance in relationships, although a few studies refute this. An increase in homosexual behaviors is sometimes shown. Women with CAH marry and procreate less, but social inhibition due to unusual genital appearance and hirsutism could contribute to this. Both sexes are reported to be more likely to be left handed, but normal patterns of brain lateralization prevail. There have been several studies revealing a very high rate of psychiatric illness in males with CAH, which interestingly, is much higher in those who did not receive cortisol in infancy, i.e. with the same hormonal milieu during development as with CAPS. Much of nonclassical CAH (NCCAH) remains undiagnosed, so this would be an ideal population to study. Female infants with mild NCCAH have no virilization at birth and often longer ring fingers than index fingers are noted. Clinically, they resemble non-treated CAH patients if they are diagnosed.
All of these findings jibe with what I have observed in the CAPS population. Further, many folks who are heterozygous for this mutation or who have mild CAH which was not treated in infancy have reached out to me since the release of the RCCX Theory. What they reveal resonates with the description of CAPS, including the sexual aspects. The RCCX genes may hold the key to many of the mysteries surrounding biological versus cultural features of gender identity and sexual orientation.
To take this line of thought a step further, I actually believe that the RCCX genes may create people who are distinctly different from a gender standpoint. While both sexes are androgenized, some of the men may have a greater influence of 17hydroxyprogesterone on their brain development and function. The most salient effect of these hormone perturbations would be on gender identity and interestingly, high androgens and high rates of PCOS have been found in female to male transsexuals. I suspect that this can also affect sexual preference and even sexual attraction. It is quite plausible that this sex hormone overlap may offer an evolutionary advantage in terms of enhancing communication between the sexes.
It is quite clear that people with CAPS choose each-other, and while I have been saying that this is likely due to a similar world-view, there could be a sexual/hormone component to this as well. The pairing of 2 CAPS individuals greatly increases the risk of having children who are homozygous for the CYP21A2 mutation. The would greatly increase the risk of an inappropriate stress response and perhaps, chronic illness at an earlier age or with less of a trigger.
C4 Mutations Likely Effect How Primary CAPS Presents:
C4 mutations also most likely contribute to the adaptive and at times maladaptive responses to stress in people with CYP21A2 mutations. As mentioned above, CYP21A2 mutations frequently co-segregate with C4 mutations, so it is quite common to have people with both mutations and medical conditions/physiological states associated with both. C4, the protein gene product, is involved in dendritic pruning, the removal of connections in the nervous system which allows the brain to grow and change as it matures or faces new situations (neuroplasticity). C3 (another complement protein from another gene) is deposited on synapses which are to be removed and C4 is directly involved in directing the activated microglia to engulf the synapse. C4 mutations can affect the amount or characteristics of the C4 which in turn, would affect dendritic pruning. This is felt to be pathogenic mechanism in the development of schizophrenia. Clearly, what I am discussing above in terms of CYP21A2 associated changes in brain structure and circuitry may be affected by how C4 is functioning (i.e. the presence of C4 mutations)
I have found that there are secondary effects from this wiring, meaning that CAPS can predispose to different outcomes, some of which are specific DSM diagnoses. The outcome depends on the severity of the acute stress response, negative life experiences and the presence of brain inflammation from 21hydroxylase overwhelm (I believe this is happening based on co-occurring symptoms).The CAPS brain is set up to be very much affected by experiences so that life events can have a tremendous impact. Invalidation from others with lesser acute stress responses (often parents and later doctors, can be very damaging). Additionally, the strong emotions from the enlarged amygdala can be positive or negative, depending on outlook and life experience.
Extremely sensitive people with CAPS are born over-stimulated and fearful due to an acute stress response which is too high for comfort. In low danger environments, this especially sensitive person with CAPS may see threats everywhere and neurotically obsess about them, burning through tremendous amounts of cortisol and racing towards chronic illness; they move out of primary CAPS into the secondary category almost immediately. Due to the exaggerated acute stress response, memories are stored with a tremendous amount of affective and autonomic information and reverberating threat circuits are easily induced.
In very high stress, negative environments which are unremitting, constant adrenaline release can result in extreme hypervigilance/overarousal, even in a person with only a slightly exaggerated acute stress response who previously enjoyed daring activities. As negative memories are accessed, the stimulating affective and autonomic information turn on the acute stress response and trauma generalization occurs as the aversive memories now pervade the previously neutral environment where they were accessed. This sort of generalization is universally described in the PTSD literature and is blamed on the presence of high arousal/catecholamines during events. With generalization comes further threat wiring enhancement with dissociative circuits (limbic and brainstem), worsening dysautonomia, and now, sometimes, even shutdown under stress can occur. Hallucinations stemming from these memory networks are often inaptly ascribed to chronic psychotic conditions like schizophrenia. Now, sometimes under stress. altered states without access to cognitive reasoning can occur,
Of course, this person is also ripe for 21hydroxylase overwhelm with high CRH-induced catecholamine elevations further accelerating the development of PTSD wiring, and both paths lead to chronic illness. So, while this brain is associated with some great gifts, with negative experiences, this brain can become a minefield. The psychiatric literature is starting to describe some of fall-out in the hypermobile population.
In my patients with secondary CAPS, I see:
More intense acute stress responses lead to insomnia with worsening dysautonomia and adrenaline dumping. Hypomania and sometimes mania can ensue. This goes with the demonstration of kindling in bipolar disorder, i.e. increasingly more severe symptoms over the lifetime. There is a high propensity for self-medication with substances to alter this experience.
The exaggerated stress response wires in phobias and threat brain circuits are reinforced resulting in severe PTSD symptoms including hyper-vigilance, worsening dysautonomia with flight/fight (sympathetic nervous system), freeze (sympathetic and parasympathetic) and shutdown/submission (opiates) responses which occur automatically with conscious and unconscious triggers. These dissociated brainstem and limbic system circuits produce intrusive dysphoric emotional states, dramatic visual flashbacks (Can seem hallucinatory. They are not always memories-can be dreams), motor threat responses like dystonia, cataplexy, catatonia, non-epileptic seizures, tremors, paralysis, etc., sensory issues like non-dermatomal sensory symptoms, nonspecific brainstem issues like vertigo, nausea/vomiting, swallowing/lump in throat and "forgetting to breathe"/breath holding, etc. All of these can happen in response to subtle changes in the environment or even just in response to thoughts/memories/dreams. Additionally, further constriction of social behaviors also occurs.
Increased reactivity to the environment brings an inability to tolerate crowds, malls, supermarkets or even other people, in any setting. The person may start to isolate. The ability to pick up on others’ emotions now becomes a curse as the person starts to feel permeable to negativity others put out.
With increasing adrenaline, over-stimulation and trauma response to past failures, the person develops a variety of coping mechanisms, including the development of rigid rules ("control freak"), excessive perfectionism and even, obsessionalism without a goal which can be paralyzing, as there is no "safe place" and everything feels so urgent that there is no logical place to start. The common chief complaint is "I'm stuck" or "I procrastinate". Or there may be meltdowns/shut down avoidance/numbing in high demand settings, in the presence of more pronounced danger wiring or PTSD wiring.
People can become phobic of their acute stress response/adrenaline and develop obsessional worrying and compulsive harm-avoidant behaviors to prevent future bad events/acute stress reactions. They develop compulsive behaviors to redirect the focus and to soothe the nervous system after negative events by decreasing arousal. These behaviors can include rituals/rigidity, exercise, cleaning, checking, organizing, worrying and perfectionism initially helpful, but a hindrance when excessive. Other less adaptive compulsive behaviors are often tried as well. These include: compulsive eating, porn/masturbation, gaming, phone checking and Netflix streaming. I actually had a patient who would push on his eyeballs to decrease his stress levels by increasing parasympathetic tone (not recommended). Diagnoses associated with this include: obsessive compulsive disorder (strong thoughts followed by compulsive-need-to-be-performed-behaviors), generalized anxiety disorder and obsessive compulsive personality disorder (perfectionism, high standards for self and other).
The strong emotions can be very negative, with a pervasive sense that something is wrong or something bad will happen. Guilt, shame and fear can predominate. Depression sets in. Tidal waves of negative emotions can lead to meltdowns and dissociative behaviors like cutting.
A constant sense of not being safe added to mind-blindness can lead to paranoia, paranoid personality disorder. Other times, obsessionalism, mind-blindness and adrenaline can fuel stalking and love obsessions.
The under-arousal at times of low stress, associated with lower than normal basal cortisol can lead to ADD, poor focus, slowed reactions, decreased motivation. This is typically worse in the afternoon, as blood is routed to the GI tract after lunch. Some people develop compulsive behaviors to increase arousal like eating (known to be linked to lower than normal cortisol in the literature), smoking, dangerous activities to “feel alive” (cutting).
With C4 mutations, chronic paranoid schizophrenia can probably be seen.
People with CAPS have an even greater vulnerability to psychiatric illnesswhen CYP21A2 is overwhelmed (see pathophysiology diagram above):
High adrenaline/noradrenaline (dumped to keep blood pressure up, increased by CRH) associated with POTS/orthostatic intolerance
Worsening anxiety (worse if TNXB mutation/hypermobility present due to lax blood vessels and blood pooling)
Higher risk of developing PTSD and PTSD itself is associated with an elevated sympathetic nervous system tone (increased startle).
Mania, and sometimes accompanying psychosis, if MCAS is present.
With prolonged stress or a very strong acute stressor, there may be atransitional phase with large oscillations between the acute stress arousal and the low arousal state. A widening gap between now prolonged acute stress response arousal and low basal arousal can create clinical bipolar disorder picture with vacillations between low and high energy/arousal states which occur over days or weeks, dependent on external or internal stressors.
The low arousal state often becomes more prominent as 21 hydroxylase activity becomes increasingly impaired and presumably as the Cell Danger Response remains activated. Many of the compulsive behaviors to cope with the low arousal state become prominent. Depression occurs. Invalidation from doctors has a very toxic effect.
CRH pulses start to occur in an attempt to raise cortisol to a physiologically appropriate level. CRH directly alters the immune system, increases catecholamines and activates mast cells causing them to degranulate, releasing a variety of potentially toxic mediators. Histamine causes vasodilation which is met with adrenaline and subsequent parasympathetic over-response, setting up autonomic nervous system see-sawing leading to anxiety, fatigue, insomnia and wooziness. Cytokine release from the mast cells triggers brain inflammation and likely causes irritability/raging, depression, anxiety, psychosis. CRH-induced catecholamine increase can possibly contribute to mania.
Vitamin and mineral deficiencies causing psychiatric symptoms. Low magnesium can cause severe anxiety, vitamin D deficiency can cause malaise, increased pain, B vitamin deficiencies decrease ability to handle stress (MTHFR mutations can worsen this).
Chronic pain can cause brain changes resulting in depressive symptoms.
Sudden elevation in androgens (increasing after 21hydroxylase is overwhelmed) can result in acne which can be very distressing to a perfectionistic teen, resulting in worsening psychological stress. This can also increase competitiveness and irritability.
The psychological effect of thelosses and invalidation which comes with chronic illness should never be overlooked!
If a C4 mutation comes with the CYP21A2 mutation, there may beautoimmune brain issues, more autistic features and possibly schizophrenia.
In Fact, CAPS (Plus or Minus C4 Mutations) Likely Predisposes to Four Out of the Five Major Psychiatric Diagnoses and is Associated with the Fifth (linked with C4):
The RCCX Theory posits that CYP21A2 mutations may underlie the development of 4 of the 5 major psychiatric disorders, all felt to be located share a similar genetic origin, as people with CAPS are at risk for the development of:
Rumination/excessive problem solving (mood disorders)
Attentional disorders due to times of hypervigilance/increased arousal alternating with decreased arousal (ADD)
Disorders of prolonged arousal due to high acute stress response and dysautonomic circuits (mania, paranoia).
Autistic features due to "brain wired for danger"
Brain inflammation/MCAS from 21hydroxylase overwhelm can add a level of irritability, distractibility, intensity and sometimes psychosis to the clinical picture.
Schizophrenia (just mapped to C4 which frequently co-segregates with CYP21A2).
From CAPS To Mitochondrial Shutdown
So, I believe that CYP21A2 hard-wires the brain during gestation/infancy to create a brain designed for threat detection and action in dangerous circumstances, (CAPS). People with CAPS have superior pattern recognition, sensory perception, threat detection, focus, reading of emotions/intent in others, information processing and problem solving. The exaggerated threat response and enlarged amygdala create high adrenaline/emotion-driven responses to any perceived threat, consciously or unconsciously recognized.
The purpose of this variability in stress wiring is to allow for adaptation to changing environments. I believe that if the person is ill-adapted to the level of stress in their environment or if the stress is unremitting, the person is effectively removed from the gene pool. This is accomplished via CYP21A2 mutations in 2 ways: via the hormonal and inflammatory cascades associated with 21hydroxylase overwhelm AND through PTSD wiring, both of which can probably result in stress-induced mitochondrial shutdown.
Regarding the latter, with unremitting stress, it seems that CYP21A2 mutations allow for epigenetic changes resulting in further reinforcement of these threat detection/harm avoidance pathways. Reflexive emotional (amygdala, hippocampus), motor, sensory and autonomic (brainstem) memory networks become more predominant with the person reacting all of the time without necessarily being conscious of the triggers. Further shutdown of social, bonding and intimacy pathways occurs (Porges’ ventral vagal pathway), creating a PTSD clinical picture. Procreation stops and dissociative reactions (flashbacks, nightmares, fight, flight, freeze, submission, posturing/motor symptoms, emotional dysregulation) prevail. Naviaux lists “PTSD” as a major stressor which can flip the mitochondria off. I now believe that CYP21A2 mutations determine who is most at risk for the development of PTSD in response to traumatic events and prolonged stressors. By cusing mitochondrial shutdown, this PTSD-associated maladaptive wiring leads an energy shut down or black-out as the mitochondria cease making ATP from ingested food.
If the RCCX Theory is correct and CYP21A2 mutations lead to CAPS and CAPS is, in fact, a brain wired for danger (due to spiking cortisol during brain development) and primed for PTSD (as negative stress-inducing events are cemented into memory by extra cortisol and catecholamines throughout life) and if PTSD and chronic stress lead to mitochondrial shutdown resulting in chronic illness, it would be important to understand how to manage this sort of brain so that this path can be avoided. It would also be important to learn how to rewire the brain to be less threat-focused.
Many of the advances in trauma treatment make use of these techniques (see below) without directing them specifically at CAPS.
The recent discovery of trans-generational epigenetics in terms of stress adaptability has some dire implications for families with these genes ("Trans-generational epigenetics" in reference to stress response refers to gene expression modifications occurring in times of hardship which can affect future generations. For example, a great grandchild of people who experienced a famine may be obese, holding on to every calorie). If CYP21A2 expression is modifiable via transgenerational epigenetics, we must as a society learn how to decrease toxic stress in our environment or change our response to it, or the the risk of chronic illness could possibly sky-rocket, given how common CYP21A2 mutations are in the general population.
**I need to insert a disclaimer here: Please discuss any techniques you wish to try with a medical or mental health practitioner as I am unable to make recommendations over the internet. If you are having thoughts of self-harm, please seek care immediately.**
Decrease the Downstream Stress of Chronic Illness
Before I start to address how to manage some of the pitfalls with CAPS, I want to be clear that I am NOT writing about how to manage chronic illness. If we have mitochondrial issues, it is important to follow the recommendations of the mitochondrial experts for treatment. If CYP21A2 mutation-induced hormonal abnormalities are at play, hormonal treatments will be paramount. If MCAS is present, mast cell stabilizers are necessary. If pain is in issue, it must be treated. If dysbiosis is present, the gut must be healed. If particular psychiatric disorders, like psychosis, are present, then psychiatric medication is important.
I have had the unfortunate experience of being accused of saying that psychological treatment alone is adequate for chronic illness. It is NOT. Yes, I believe that an abnormal acute stress response is ultimately what makes us sick (by turning on stress-dependent physiological machinery), but I also wholeheartedly believe that all of the downstream effects must be dealt with in order to decrease the acute stress response! While managing the downstream effects, it behooves us to learn to minimize our stress…
The Acute Stress Response Needs to be Understood and Decreased
Since the CAPS brain is wired for danger, threats cause distress and turn on the acute stress response which is exaggerated and reinforces the danger wiring. If this threat is prolonged or particularly severe (EBV, Lyme, mold in some), it can cause 21hydroxylase overwhelm with a subsequent illness cascade which likely causes mitochondrial shutdown (or maintains it). I believe that this is how CYP21A2 mutations are associated with chronic illness. As the threat wiring becomes primed, the acute stress response is revved most of the day, burning up 21 hydroxylase.
It is important to understand what happens in an acute threat situation (which turns on the acute stress response). The threat is separated from the rest of sensory input, we (consciously or unconsciously) focus in on it, we may physically orient toward it, we react without thinking, then some time later, we are able to think about what happened. During this response, the amygdala (fear/emotional center in the brain) is immediately alerted with resulting fear, the adrenal glands dump adrenaline/cortisol as the autonomic nervous system takes over. The connections to the cortex (reasoning part of the brain) are shut down, sugar is liberated to provide energy for movement and the brain-stem initiates action. The cortex comes back online shortly thereafter.
It stands to reason that we might be able to prevent chronic illness by decreasing the demand for cortisol (avoiding 21 hydroxylase overwhelm) and blocking the progression towards PTSD physiology.In doing this, we may also be able to avoid mitochondrial shutdown. Remember that I believe that chronic illness is a programmed way to remove our genes from the gene pool when stress: stress response mismatch becomes large. I believe that we can do this by learning to decrease the frequency, intensity and length of our acute stress responses and by decreasing reverberations through the threat circuits in the brain while encouraging the pleasure, connection and calming circuits to strengthen.
We can decrease the frequency/intensity of our acute stress response by:
decreasing our stress load (acceptance versus change)
learning to keep our nervous system in optimal arousal, how to re-balance dysautonomia (self-care, feet up, deep breaths, etc.)
figuring out our triggers and processing traumas so that brainstem and limbic circuits integrate with the cortex and are less automatic
changing our view of life events-negative events become opportunities to learn, to do better next time rather than failures
avoiding rumination, resentment, dread (letting it go, making the decision, doing what's effective)
re-balancing quickly after an acute stress reactions by altering our interpretation of the acute stress response itself, ("oh there's that pesky hot flash/jolt response/POTS attack again, lol", "there's that CAPS brain of mine telling me I'm not safe, but I'll ground myself and remember I'm safe.")
self compassion ("My poor body is doing the best that it can".)
The CAPS exaggerated acute stress response can cause interest/excitement, anxiety/fear/dread/shame, autonomic nervous system activation (fight, flight, freeze, submission/shutdown), “turbo”/flow, hyper-focus/distraction (depends on strength) and/or insomnia/action/isolation/withdrawal, depending on how it is perceived by the mind/body.How we react to it determines how long it lasts in a negative churning form (which relentlessly burns 21hydroxylase). Below I will help with changing the attitude.
Lifestyle changes can make a big difference in terms of prevention and recovery. The exaggerated acute stress response with its high adrenaline/cortisol can make us feel invincible, and many of us live that way until we are sick. I always thought I was like some sort of superhero, pushing through everything and then collapsing here and there. If I didn't do everything at 100%, I felt like I had been lazy, and I was proud of how I could work harder than others. That was part of my identity. Operating like that with our physiology is a recipe for chronic illness as 21 hydroxylase is easily overwhelmed. Without the gauges telling us that we went too far, did too much, we have no suspicion of being in dangerous waters.
Part of recovery involves some acceptance of the fact that pre-illness functioning was probably supra-normal and it's not a reasonable expectation to wish to return to that level of functioning ever. If you get the chance to be like that again, and many of us do (because even in severe illness, the exaggerated acute stress response seems to be preserved at the expense of basal cortisol), you will quickly run yourself into the ground again. This is the gas-brake-gas-brake-gas cycle that we get into, until there is no more gas and the "wall is hit". When I hit that wall, a teeny, tiny one time dose of prednisone helps me so much (as it would if 21hydroxylase overwhelm were the issue), so I am quite sure I understand this physiology pretty well. When I hit the wall, I make a note of the fact that I was running myself way too hard and that I set myself back. Really, I should have learned this lesson by now, but when the gas/turbo comes back on, it's fun to ride! Instead, the way to recover is by slowly ramping up activity, while paying close attention to your acute stress response. It is imperative that you find your gauges and check them often.
Additionally, the PTSD wiring can rocket us into an acute stress response at every turn. On the positive side, though, even with fairly significant PTSD changes in the brain, there is quite a bit of evidence in the PTSD literature that it is possible to promote healthy epigenetic changes/brain rewiring toward resiliency and away from threat detection.
I am going to present techniques and point you in the right direction to discover more techniques which may appeal to you even more than mine do. You can accomplish all of the above and I believe this can be effective in preventing chronic illness in many of us with CAPS and allows for a better chance of recovery in conjunction with medical treatment for a good percentage of us.
I want to make it clear that no lifestyle changes can prevent chronic illness in a vulnerable person who has been exposed to Borrelia Bugdorferi, toxic mold or an overwhelming infection. However, it can possibly minimize the fall-out after exposure and can perhaps promote recovery in conjunction with medical treatment.
If you don't have chronic medical illness, feel free to skip to the General Principles as this next part doesn't pertain to you.
Considerations For Those With Chronic Illness:
While turbo, hyper-focus, and interest are positive states associated with the acute stress response, they can still burn some 21 hydroxylase. This is why when someone is very ill with chronic illness, even a tiny bit of fun or excitement has a terrible hangover. I hate to use the cliched "stress bucket" term, but it is an important concept here. Imagine that each time the acute stress response turns on, water pours into the bucket which has a small hole in bottom to drain. When the bucket is full and running over, 21 hydroxylase is overwhelmed and hormone derangement and inflammation start (for me, the first sign is eye-burning from MCAS, presumably due to high CRH).
If you have rip-roaring MCAS, dysbiosis, vitamin deficiencies (MTHFR), raised ICP or mitochondrial issues, then the tap is turned all of the way on and running continuously. Your bucket is overflowing and you must get these conditions fixed before you can expect your attempts to limit the acute stress response via psychological methods to have any effect. If you are in a bad relationship or if you have a lot of simmering anger/resentment/worry, the tap is also running constantly and the hole in the bucket is not allowing it to drain fast enough. Treating destructive processes, and giving your body what it needs, creates the safe place from which you can heal.
If you can get learn to turn off the tap quickly, the bucket has some time to drain and then you have a little bucket space for something fun before 21 hydroxylase overwhelms and the mast cells rear up. As I have improved, this is 100% the case, although, truth be told, too much time spent working on this website (which I enjoy) has had a very negative effect on my health.
Ultimately, we want to send the signal to our brains and our bodies that the stress:stress response mismatch has resolved and that our genes deserve to be part of the gene pool.
This is not easy once chronic illness starts. Often in CAPS, physically healthy people are more likely to report positive associations (interest, excitement, flow, hyperfocus, action) with the acute stress response, while those who are starting to decompensate physically and/or psychiatrically will report more of a tendency toward the negative aspects (anxiety/fear/dread/shame), more pronounced ANS dysfunction and less adaptive behavior (more withdrawal and isolation). Not surprisingly, epigenetic brain changes associated with an exaggerated stress response coupled with negative experiences explain the latter response as they are suggestive of worsening PTSD-like symptoms reflecting the development of primed threat circuits.
For most of us with chronic illness, the acute stress response has a hair trigger, the amygdala response is dramatic, the adrenals dump even higher amounts of adrenaline/cortisol presumably due to primed fear circuits and high CRH in the setting of lower basal cortisol. My clinical experience very much suggests that there are often dissociative circuits involving the limbic system and brain-stem which produce unusual patterns of dysautonomias, emotional responses and motor actions, often completely separate from cortical control (reasoning) for a good bit of time. Also, as mentioned above, I believe that 21hydroxylase is more likely to become increasingly overwhelmed, not meeting the body’s need for basal cortisol, driving CRH up further. By increasing catecholamines, CRH increases anxiety and probably increases brain inflammation/irritability via a direct mechanism and through mast cell activation. The difference between basal cortisol levels and acute stress cortisol would become more pronounced, making the acute stress response seem like someone is stomping on the accelerator, while riding the brake most of the time. When 21hydroxylase is completely overwhelmed, “the wall is hit” and with acute threat, the person is unable to mount any sort of active response. In this state, anxiety and arousal are also very prominent because our bodies are responding to dangerous conditions developing within them. As we become more impaired, we are negatively affected by any perceived demand because we know we are very limited in what we can handle and we fear "hitting the wall". Clinically, I have experienced this and have seen these clinical effects in patients as well, many times (also responding to one tiny dose of prednisone when the wall is hit.). I am sure that these effects are due to this underlying pathophysiology.
I believe that those frequent jolts that we get (often in association with a hot flash), sometimes out of the blue and at other times when we think about anything even mildly alarming or exciting, are actually acute stress responses. Because we can physically feel them, we can start to panic when they happen because they signal to us just how sick we are. It's a vicious cycle.
Ironically, though, because we can physically feel them, we can figure out what brings them on and what modifies them.With this chronic illness, we now have gauges we lacked before! I am quite open with my patients about how these jolts allowed me immediate feedback regarding my internal state, and thus, provided a wonderful feedback mechanism regarding how well I was using my DBT, mindfulness and grounding skills. I still get them, but I don't miss a beat and they resolve quickly with very little residue in terms of fear, dread or churning.
Before I start, I want to say something that my horse trainer used to say all of the time because it is the most important principle on this journey. "If it's not working, you need to change it up."
Did I say above that people with CAPS can be stubborn? We love to figure out the best systems for doing everything and then we are resistant to changing them, even when they become maladaptive. Most of us struggle with change as change can rev up the acute stress response and once we are sick, we especially don't tolerate that well.
However, once we start having chronic illness issues (medical or psychiatric), we MUST change what we are doing because for many of us, our previous lifestyle had something to do with getting us sick (unless of course, we had some toxic exposure, EBV, Lyme or a traumatic accident). Even if it didn't, we literally are not able to do what we could do before. The sooner that one can accept the illness and start doing what's effective, the less damage will be done.
When I got sick, I knew very little about the acute stress response, as I was more of a medication-management psychiatrist, interested in manipulating neurotransmitters. Early on, though, it was very clear to me that the acute stress response was a central aspect of this chronic illness, as I felt much worse when I was under stress. It occurred to me that the techniques used to treat PTSD would be very relevant. Now, after learning about the RCCX module, I believe that our pathophysiology is actually nearly identical to PTSD. Learning to recognize when the acute stress response is turned on, how to modulate it and how to change our response to it is a big part of recovery. Figuring out how to do this is a very individual process.
It is vital to develop an awareness of how your mind and body work and what turns on your acute stress response. Then, it's about finding what works for you (makes you feel better) and doing it ALL THE TIME.If you are getting stressed out because you are telling yourself "I have to meditate every day" and you hate meditating, then it is a perceived demand and guess what, the thought that you have to meditate is now causing a churning acute stress response! You don't have to do anything that you hate to get well, but you do need to figure out how to incorporate a healthy dose of grounding/mindful activities (see below) which you enjoy every day into your life. Along the way, you will want to increase your self compassion, learn to make active choices about who/what will have access to your time/self and try to live in the present moment as fully as possible. Additionally, you will likely choose to eliminate a few toxins from your life, i.e. those things which you notice jack up your acute stress response (often multi-tasking and cell phone alerts). Again, how we accomplish these goals is different for each of us.
What I did: After extricating myself from as many stress-producing situations as I could (changing jobs, etc.), it was clear that the next step involved working with my mind to decrease my reaction to the reality of my illness, as my level of alarm directly correlated with worsening function. I read many books and tried many different techniques, seeing what worked best for me. I never could formally meditate, clear my mind, force negative thoughts away or do yoga. These can be wonderful, invaluable techniques, but not possible for me. I lower my acute stress response and balance my nervous system by: connecting with the animals (petting them, hearing their heartbeats, playing with them), riding my bike while changing my focus (spotlight, see below) from the music I am listening to my legs, to the horizon, to my breathing, etc., sitting on the patio separating out bird calls (otherwise in silence), keeping track of which plants are blooming, focusing all of my attention on making a salad for lunch, getting into a flow state with a creative project broken up into small enough pieces that I can accomplish a distinct piece, etc. I know that the cell phone jacks up my acute stress response every time it has an alert, so now, I turn off the ringer and only check it every couple of hours. There are many other changes I have made. Each change is a decision which I consciously make.
Just because I may have figured out the gene running the show doesn’t mean that I am the only person who can treat all of this. Many different kinds of mental health providers can offer help with a variety of techniques which incorporate this awareness, grounding and self compassion. They have written books, published articles, and blogged about them, so I don’t need to go into a huge amount of detail about what exactly you need to do, other than to point you in the right direction. Again, the treatment plan needs to be individualized based on your preferences. Many excellent resources are free. You will actually be changing the way you view the world and practicing techniques to do this, rather than necessarily enrolling in a program to be fixed. I will direct you to some of the excellent resources that are out there. There will be many more resources and techniques than I list here. I'm going to stick with resources which have some research documenting their efficacy and which I have tried (as I am a doctor, I need to stick with evidence-based), but there are many other resources which may also be very helpful (e.g. energy therapies).
Overview of Hierarchy Of Specific Techniques/Resources Which Benefit All of Us With CAPS, Sick or Not **This is in order of importance.**
Establish sense of safety, efficacy, self compassion.This is along-standing, over-arching goal and a process which involves all of the other steps. It is the single most important goal. Grounding (see below) and cognitive behavioral therapy to start. Start with safety in the self/body, then expand to outside world and keep expanding...
Recognize positive aspects and vulnerabilities of this "wired for danger" mind.
Self-care to optimize physical and mental health, keep autonomic nervous system regulated, Self compassion!
Learn and practice grounding skills. Once you can do them, push your boundaries a little. Learn a new skill which give you a little thrill and play with altering your acute stress response. If you have chronic illness, practice these skills when you have a disconcerting symptom (like with those horrible jolts of anxiety we get with the accompanying drenching sweat attacks).
Learn and practice mindfulness ("non-judgmental awareness", memorize that definition, see below) at all times. Being present and choosing where to direct your focus, to internal and external experiences. (Of Note: this is not focusing on unpleasant sensations in the body and it is also not suppressing those sensations. Instead, it is making room for those sensation by choosing to focus your spotlight (all of your attention) on something else, making room for the unpleasant sensations. I know that mindfulness has gotten a bad reputation in the chronic illness population and that's because of therapists who have a limited understanding of the concept, trying to teach inappropriate methods for people with pain and trauma. If you think of the spotlight, see below, you can't go wrong.)
Make informed decisions about how to manage your life, including who or what gets access to your time, resources and sensitive heart. Everything you expose yourself to is a choice.
Bolster organization/prioritizing skills as everything feels urgent but really isn’t! Very little really needs to be done perfectly, but everything should be done with intention and attention.
Stress Management Essentials: Russ Harris: Acceptance and Commitment Therapy (ACT): : Dropping the Struggle, Making the Decision, Acceptance Versus Change (yes, it is one or the other), Doing What’s Effective.
Social connection: people OR animals (if humans are too complicated), compassion and loving kindness towards others strengthens positive pathways. Lose expectations and judgements about self and others.
Learn Dialectical Behavior Therapy (DBT) skills for emotional regulation.
EMDR/other experiential trauma work for integration of limbic and brainstem responses to triggers (conscious and unconscious)
CBT for dysfunctional beliefs about the need to be perfect, to be liked, that you did something wrong, as these beliefs increase the stress response for no good reason. The pitfall of CBT alone is that it assumes that a thought precedes the acute stress response and this is not always the case, as I have pointed out above. Many times, the acute stress response is triggered by an unconscious cue and the first thing which happens is that the cortex (thinking part of the brain) goes off-line. CBT is good for the reverberating cognitive circuits which result in the acute stress response revving in the background, i.e thoughts like "I am useless", "I will never feel better", "I am not important", etc. Also, grounding techniques can turn on the cortex after an unconscious trigger and then CBT can deal very well with the negative thoughts which often accompany an acute stress response.
Top Notch Resources: (If you are chronically ill and have secondary CAPS, I'd use them all!)
Russ Harris, The Happiness Trap (Acceptance and Commitment Therapy, Acceptance versus Change, Drop the Struggle, Acceptance versus Change, Do What’s Effective, Mindfulness)
Elaine Aron, Highly Sensitive Person Books
Matthew McKay, etc. DBT Skills Workbook (DBT Skills for emotional regulation, mindfulness)
Jeffrey Young, Reinventing Your Life (CBT, addresses schemas holding dysfunctional beliefs)
Brene Brown, TED Talks for perfectionism and shame
For PTSD (most of us have some degree of PTSD wiring)
Suzette Boon, etc. Coping with Trauma-Related Dissociation: Skills Training For Patients and Therapists
EMDR Institute has a provider list to find local practitioners who have adequate training: http://www.emdr.com/find-a-clinician/
For Chronic Illness
Toni Bernhard, How to Be Sick (self compassion, mindfulness, acceptance for those with chronic illness)
The Details: *Remember that this is in order of importance.*
Establish sense of Calm, Safety, Efficacy.This is along-standing goal and a process which involves all of the other steps. It is the single most important goal. (This has a corrollary: "learn to be calm in chaos"). I will go through the steps, but the first step is to work toward a constant state of mindfulness, remember that this is "non-judgmental awareness" (MEMORIZE that definition). You need to be aware of your internal and external states in order to work with them. If you are phobic and suppress them, I promise you that they will ambush you in the middle of the night. More about mindfulness below. With this brain, you often feel as if you are under constant threat, both physically and mentally. Remind yourself that your body is jacked up on more adrenaline than you need. Just because you feel like you are in a life and death situation, doesn't mean that you are. This is a tough one because if you have chronic illness, you do have some serious health stuff going on. The symptoms can be incredibly alarming and can be due to things like raised intracranial pressure with brain-stem compression (as you know, I had that!). But even if you have that, you aren't doing yourself any good by jumping on the adrenaline train because it is just heading to 21 hydroxylase overwhelm, more issues and maybe mitochondrial shutdown. When you have sky-high noradrenaline and adrenaline, it is very hard not to jump on the train. The grounding skills aren't near as powerful as you may hope, but you need to stop, hydrate, take some salt ( if BP ok), put your feet up, do some deep breathing and focus on the horizon, reminding yourself that it's OK. Feel compassion toward yourself and your poor body which is doing the best it can.
If your mind tells you that you aren't safe even when you are, remind yourself that this is the mind which finds the one ink stain on the rug, the scratch in the new car's paint. It is wired to do this.
People with significant attachment trauma or repeated medical/family invalidation of their illness or feelings will have a difficult time establishing inner safety and will likely require a professional to assist with this, but the skills remain the same and you will find them below.
Grounding skills are essential. As you will recall from above, the cortex (the thinking part of the brain) is often off-line when the acute stress response is turned on. Grounding skills are used to turn it back on (see below). In order to feel safe, it may be necessary to ground yourself every couple of minutes, especially if you have PTSD. In the latter case, anchoring objects, familiar belongings with positive associations can also be very helpful. Once grounded, DBT, ACT (Russ Harris), CBT are used to help with the unhelpful thoughts which occur when the body/mind is over-aroused (see below). Self compassion must follow... Safety starts with self/body, and then expand to outside world and keeps expanding...It must expand in order to get better...
Establishing a safe place, a place in the mind's eye which is always calm and peaceful allows for a retreat when the world becomes over-stimulating.
Recognize positive aspects and vulnerabilities of this "wired for danger" mind. I think I outlined these fairly well on this website. It is important that you understand how this mind/body works in order to use mindfulness ("non-judgmental awareness"). If you see the positives, it may be easier to accept the negatives without getting stuck in the unhelpful thought that you are cursed or that your mind/body is failing you or is hateful. Remind yourself that this is a carefully constructed and designed mind/body which is responding in the best way that it can under these circumstances (self compassion). I often tell my patients that everyone else is driving a Ford F150 and they are driving a fancy Italian sports-car which requires an adjustment every time it is driven. It is also vital to read and understand the manual.
Self-care to optimize physical and mental health, keep autonomic nervous system regulated, Love and compassion toward yourself! As discussed above, we are very prone to dysautonomia, an exaggerated stress response (high arousal, fight/flight usually) and low basal cortisol between events (low arousal). Dysautonomia can involve an elevated sympathetic nervous system (i.e. POTS, gastroparesis), see-sawing of the autonomic nervous system between rest/digest and fight/flight; freeze which involves both systems being turned on high or even submission, in which opiates are high. High arousal is often associated with anxiety, and sometimes exhilaration, and low arousal is often associated with fatigue, poor concentration and sleepiness.
With our internal states all over the map, we must develop some skills to regulate this and our response to it, in order to feel safe. Most of us have already developed some of these skills without even realizing it! We drink lots of coffee, we rock/squirm, we put our feet up, we love music, we drink alcohol, we eat, we check our phone every 10 seconds. I always point out which of these techniques I am observing in my patients during their appointments with me in order to help them develop mindfulness ("non-judgmental awareness"-I will get you to memorize this term by the end). If you notice what your body is doing and your responses to it, you will be less caught off guard if more drastic changes occur. In fact, you should be able to anticipate and even avoid most of these changes by intervening before they occur. Awareness comes first!
Good self-care can help with this quite a bit by avoiding fragile physical states associated with adrenaline-dumping or exhaustion. The goal is to keep the autonomic nervous system closer to an optimal arousal zone by decreasing the factors which really make it unstable. We do this with:
good sleep (see Alan Pocinki's video about Sleep and Dysautonomia, very relevant for all, chronic illness, EDS or not)
adequate salt and water repletion
taking propranolol 10 mg prn if adrenaline dumping is an issue and if not contraindicated
using positional changes to enhance blood return to the heart (legs up, get up and walk)
engaging in deep breathing and other grounding techniques if anxious/aroused
daily exercise to increase parasympathetic tone (no matter how little you are able to do)
dividing tasks into manageable pieces so they don’t run too long or seem overwhelming. Sometimes alternating tasks which require different levels of arousal. This is NOT multi-tasking. Focus all attention on one short task or part of a task and then put all of your energy /focus on the next (e.g. read 10 pages, then lift weights, then back to reading/studying).
avoiding sensory over-stimulation or at least balance with silence/calm. Learn to be calm in chaos.
making sure magnesium is repleted (low magnesium increases adrenaline)
scheduling quiet time to get into flow (coloring, artwork, meditation, music, TV or video game playing but in moderation)
Turning the cell phone alerts off and checking the phone at set times if you can! (Each alert triggers an acute stress response!)
Others for the brain/body: B vitamins (if concerned, check for MTHFR mutations and supply appropriate formulation), vitamin C, vitamin D (follow levels, calcium levels and symptoms), zinc
Learn and practice grounding skills. As mentioned above, "learn to be calm in chaos". Grounding is a powerful tool to accomplish this.
"Grounding" is also a very powerful way to decrease over-arousal. It involves providing and focusing attention on sensory input. You can smell something, taste something, touch something, name something you see or just notice your breathing. By focusing your attention intensely on a sensation when you are over-stimulated, you shift the brain processes away from the emotional centers and automatic brain-stem responses and reconnect the cognitive processes. Some people will carry an oddly shaped rock with interesting textures in their pocket just for this purpose. Focusing on breathing can have a dual purpose; it can be a grounding technique and it can increase parasympathetic tone immediately, counteracting the adrenaline of the acute stress response. Breathing is always available, so it can be used in the "heat of the moment" at any time.
I like Russ Harris's tree analogy to keep the grounding skills in mind: Feel your feet (the roots) as they push into the ground, keeping you firmly planted, then breath and act through your center (the trunk), balanced, then reach out to the world with the branches for sensory input.
Use the grounding skills any time you feel over-stimulated. When you get good at it, you can put yourself in stimulating situations and see if you can calm yourself. Riding my horse (prone to small spooks) and seeing patients whilst having those anxious jolts/sweats keeps me in practice. This is part of expanding the safety from yourself to the world. You can't live in a bubble, trying to avoid acute stress responses. You need to increase your ability to handle these response and regulate them when they occur.
Learn and practice mindfulness. "Mindfulness", again, is simply "non-judgmental awareness" or the "observing self", a profound concept.
Some people mistakenly think it is meditation or clearing your mind or solely focusing on bodily sensations which can be good for some people, but not good if you have chronic pain! Meditation and clearing one's mind is very difficult for people with CAPS who are very thought-driven, and while mindfulness does involve shifting attention, focusing on bodily sensations when one has chronic pain is ill-advised. Please open your mind to the concept of mindfulness, despite what you may have heard or if you had a therapist who introduced it inappropriately. It will help you!
I really like an analogy that Russ Harris (The Happiness Trap) uses for mindfulness (the Hexaflex): "Life is like a stage show and on that stage are all your thoughts and all of your feelings, and everything you can see, hear, taste, touch and smell."He tells you that you are in the audience (separate from the stage by distance) and you can choose to direct the spotlight on anything you choose.You have non-judgmental awareness of what is on the stage but you are separate. You can choose to look there or choose somewhere else to look.
Eckhart Tolle writes of feeling like "I can't live with myself." Then he realizes that "I" (observing self) can't live with "myself" (all of the other chatter that goes on in the mind, all of the junk on the stage of the stage show.) Without "myself", "I" would be content.
If you can develop your observing self, you will have some distance from all everything that can permeate your thin CAPS skin. You can throw whatever/whoever is bothering you up on the stage and feel the distance or you can direct your spotlight somewhere else. In my therapy sessions with patients, I ask them to bring in upsetting events for discussion. I model throwing the event, all of the players and all of the emotions up on the stage. I then help them see the whole situation from the perspective of sitting in the audience and choosing where to direct the spotlight.
Directing the spotlight is very helpful for dealing with pain or other unpleasant bodily sensations. I practice this when I ride my bike. I focus on the horizon, looking at the colors of the mountains, then I focus on how my legs feel as my muscles work, then I focus on my breathing, taking deep breaths to expand my collapsed EDS lungs, then I run through my patients (thinking about how I am going to address their issues). Sometimes in the heat, while going uphill, I am confronted with the thought "I think I might die". To use a Russ Harris technique, I decide that this thought isn't helpful and I focus my spotlight on something else. At the dentist, I focus my spotlight on the tree outside the window, imagining that I am an ant deciding which way to go on each branch. Looking off into the distance or at clouds can be more helpful for pain than looking at something up close. It makes room for the pain, so to speak.
You can practice mindfulness and focusing the spotlight any time, any place. When you do something, anything, try focusing ALL of your attention (the spotlight) on that task and experience everything about it. You will find that this refreshes you. I actually cravethese activities after being pulled in all directions for a day or two (part of my job, unfortunately.) The CAPS brain is so ADD/distractible that unless it is really focused on something, it's burning energy. Multi-tasking is increasingly difficult for us as our acute stress response becomes higher. If you can only last 5 minutes fully focused on something, then go fully focus on something else. This is "serial tasking"-I think I just invented that term. I tend to do tasks which require different skills and different levels of arousal in rotation, giving each my full attention (read 10 pages, clean the bathroom, answer phone calls, do one set of weight lifting).
Make informed decisions about how to manage your life. You decide who or what gets access to your time, resources and sensitive heart. You need to keep in mind that without good mindfulness and grounding skills, you have very thin/no skin and decisions must be consciously made with this in mind.
It sounds silly to say that you should make an effort to avoid traumatic events, mind-altering drugs, toxic people and situations which make you feel helpless, but some people have to be told that before it will occur to them. To understand how powerful our negative memory storage can be, let me tell you that I saw a squirrel get run over during my college interviews in 1983. I still get flashbacks of that event at least once a week! I can’t tell you how many times patients have told me about similar haunting images they regularly experience and some of them never even actually happened; they are images from bad drug trips or even nightmares. Of course, I had no idea this squirrel was doomed, so for me it was unavoidable, but as part of the thrill-seeking, invincible, adrenaline junkie aspect of this brain, some people voluntarily put themselves in dangerous situations. I have seen many people with CAPS who have experienced/witnessed events which will haunt them forever. I have also seen plenty of CAPS children develop a bathroom phobia after seeing a very popular horror film about a monster in the toilet. If you have to drive by the scene of an accident, don’t look and cover your children’s eyes. If something horrible happens to you, get help, take care of yourself.
The flip-side of this is that it is very important to try to feel safe in as many situations as possible and not to shy away from new experiences which can bring mastery. I thought I was going to really lose it when I went scuba diving for the first time. I do not like to have anything over my mouth, affecting my breathing. I had to use all of my skills to get through it and boy, was it worth it!
Elaine Aron's Highly Sensitive Person books are wonderful for helping to structure a life around sensory processing sensitivities.
Bolster Organization/Prioritizing skills as everything feels urgent but really isn’t! Very little really needs to be done perfectly, but everything should be done with intention and attention! Life gets away from all of us at times and we have to go into crises mode just to keep everything together and moving forward. Despite this happening by necessity here and there, it is very important to recognize when this is going on and to make sure it is self-limited, especially if you are having symptoms of 21hydroxylase overwhelm. "Crises mode" refers to riding your acute stress response.
It behooves you to learn to prioritize and actually schedule some prioritizing time every day. Teach your children who are not sick to do this so that it becomes a habit. Plan for big projects so that they can be broken up into manageable tasks and put away after each section is completed (turning off the acute stress response associated with working on it).
We tend to feel a sense of urgency as each new task presents itself. Some of us want to jump right into new tasks and knock them off the list right away, forgetting about other important urgent tasks which really should be given priority and will really stress us out if we don’t get them done. If the task takes less than 3 minutes, go for it, otherwise keep a prioritized list at all times. Add to the list each day and make time to look at it each morning to make sure it is prioritized correctly.
Tackle each task on the list in order or according to what sort of energy you have (if you are too exhausted to focus and read, then skip that reading assignment and move down the list to grocery shopping.) If you know what you have to do and what the priority is, then you waste less energy/acute stress response worrying about everything you have to do and wondering if you are missing something. That thought about missing something and the panic/dread that goes with it is automatic for us with that PTSD brain. The more we allow it to go on, the more hard-wired it gets.
When you do a task, break it into manageable pieces that you can do all at once and be in the present moment, only focused on that task while you are doing it. As mentioned above, focus on the sensations of doing the task (water on hands if washing dishes, for example) and enjoy it. If other thoughts come up, let them go and go back to the sensations of the task at hand. (I carry a notebook with me and write down thoughts/ideas which come up during other tasks, so I can revisit them later when setting my priorities). If you wake up really ill or with terrible brain fog, you will have your list and know what NEEDS to be done that day.
Stress Management Essentials: Russ Harris: Acceptance and Commitment Therapy (ACT): : Dropping the Struggle, Making the Decision, Acceptance Versus Change (yes, it is one or the other), Doing What’s Effective. I strongly encourage you to invest in Russ Harris's The Happiness Trap. It contains so many wonderful rules for decreasing the stress response and the CAPS brain LOVES rules which work! I can't even begin to summarize the rules, but I will try to demonstrate a few.
So, there you are, going along, washing the dishes, feeling the water on your hands and… your friend calls and invites you to meet her for coffee in 2 hours. You remember that she can be exhausting because all she likes to do is talk about herself and it's a hassle to get cleaned up and leave the house. But she is one of your few friends who still calls since you got sick, and there have been really good times with her in the past. You tell her that you don’t know and you’ll call her back. The acute stress response is in action.
You are past the initial part as you have grounded yourself. Your thinking brain is online. You are arguing with yourself, feeling increasingly worked up. You need to drop the struggle. There is no right or wrong decision here in terms of whether to go. But the decision does need to be madeas soon as possible because your 21 hydroxylase is being used up and your nervous system is getting jacked up. You have all of the information (and if you didn’t, you would make the decision to shelve the decision: imagining packing it up and actually shelving it).
So, if you decide to go, you must drop the struggle by not thinking about it again until it is time to get ready to go. If you decide not to go, release the guilt. I am telling you not to second guess your decisions. It doesn’t do you any good and it burns up 21hydroxylase. If you go, it is very important that you are fully present there, spending time with her, not thinking about what a bad decision you made and what else you could be doing. If she is self-centered and a jerk while you are there and you start feeling resentful that she is taking up your time. You need to intervene. In your mind, throw her up on the stage (mindfulness, remember "non-judgmental awareness") and you recognize resentment. You know that this is a toxic emotion for you (along with seething anger, feelings of invalidation, etc.).
Whenever one of these toxic emotions/situations comes up: dangerousness, helplessness, invalidation or resentment for example, you must think about "acceptance versus change" because these are like sticks of dynamite in the acute stress response fire and can't be allowed to simmer for any length of time. Acceptance is that you will still continue to maintain the friendship because her good qualities outweigh the negative. Change will involve no longer maintaining the friendship by meeting her for coffee or anything else in the future, but you will continue to be polite.
You make the decision and by doing so,the resentment is dropped because you have been proactive. If you have decided for "change", you allow yourself to leave at the first non-rude opportunity. I say “non-rude” opportunity because it would not be effective to point out to her that she is being a jerk. She will likely have no insight, will bring up upsetting issues and it will be difficult to be around her from now on. It would not be effective to make her into an enemy. Thinking about enemies burns up a lot of cortisol. Wouldn’t you rather have it for something that enhances your life? (Do what's effective!)
Whichever you choose to do (acceptance versus change), you will continue to use the grounding tools to calm your nervous system (sensory input, focus on the breathing) and you will use mindfulness again (put her up on the stage away from you while you try to have compassion for why she is so self-centered) to decrease your stress response. You will also use cognitive skills to deal with any unhelpful thoughts about the situation "I wasted my precious resources on coming here.I won't be able to do anything tonight, now." The spoons are spent and you can't get them back. But you won't spend them next time!
Social connection: Close, strong, intimate connections are very important for rewiring those connection circuits that fade with PTSD. These social connections can involve people OR an animal (if humans are too complicated). Compassion and loving kindness towards others strengthens positive connection in these brain circuits, making them come on-line more easily in the future. Let yourself feel the positive emotions of connection and love.
Listen to your pets' heart beat, feel his fur against your face. Really watch him/her. Spend focused time with him/her and schedule it if you need to. Turn off the phone. My horse can be an ornery creature and if she doesn't have your full attention, she will not cooperate and she may actually eject you. She was an essential part of teaching me about the importance of focusing my spotlight, allowing me to experience each task fully and in the moment (the key to allowing the stress bucket time to drain).
Learn Dialectical Behavior Therapy (DBT) skills for emotional regulation. Buy the workbook and work your way through it. It starts at a very basic level of distress tolerance and builds from there. I believe most people with CAPS will find something useful in it. Our degree of mind-blindness can make even the most sophisticated among us need some skills. There are intensive DBT therapists in most metropolitan areas if you would like more intensive help with emotional dysregulation.
EMDR/other experiential trauma work for integration of limbic and brain-stem responses to triggers (conscious and unconscious) Trauma therapists often argue that it is impossible to connect up the limbic and brain-stem trauma circuitry to the cortex solely through talk therapy. Employing grounding and mindfulness in day to day life can help connect existing traumatic memory networks to the cortex and they can also discourage the development of further traumatic networks by decreasing the degree of activation, the level of catecholamines and the experience of helplessness which serve to cement alarming experiences into the nervous system.
Additionally, there are several specific techniques for processing trauma which use experiential methods. It is important to find one which works for you. I can not vouch for the efficacy of any method other than EMDR for which I received training. I do believe that the other methods work very well, too. Attachment trauma is especially important to work through as it can hinder relationships and connections which are so vital to recovery and block any sense of safety with other people. Qualified EMDR providers can be found at: http://www.emdr.com/find-a-clinician/
CBT for dysfunctional beliefs Reinventing your Life by Jeffrey Young can help you figure out which maladaptive schemas (belief systems you are holding onto as a result of past experiences: about the need to be perfect, to be liked, that you did something wrong, etc.) These beliefs increase the stress response for no good reason and should be addressed. CBT based therapists are plentiful.
Specific Populations/Special Considerations:
The young/non-sick CAPS folks pose a bit of a problem because while they are at risk for progression, they feel invincible due to all of the adrenaline-dumping they do. When I see them in the office, it is usually because of anxiety associated with a short-lived acute stress response situation like exams or a failed romance. In this “teaching moment”, I emphasize their stress vulnerability, the importance of avoiding habits which bring negative experiences, as well as all of the techniques on the list above.
Some of young/non sick CAPS people are thrill seekers who enjoy the high of the exaggerated acute stress response when they are in control of it. I have treated quite a few motorcycle racers, pilots and 4 wheelers with this brain. I don’t discourage these activities as they are short-lived, not particularly harmful (as long as they don’t have an accident) and may actually have beneficial effects. This brain would lend itself very well to these activities as long as it is not too intense and the sense of mastery attained may serve to decrease the acute stress response in other situations. Learning how to excel in exciting/challenging situations while practicing grounding skills to lower arousal allows a sense of self efficacy and safety under pressure to develop. Additionally, being able to lower arousal on command is a vital skill for the CAPS person to have as it may actually decrease the risk of PTSD wiring or 21hydroxylase overwhelm in the future. We know that the development of PTSD is dependent upon a high level of arousal and a feeling of helplessness.
Some people with CAPS live a restricted, harm-avoidant life from day one and are not able to even tolerate the excitement of going to the store or going to school. These people are born with a greatly exaggerated stress response. First, they need to develop grounding skills to decrease arousal. For them, it is vital that they develop a sense of safety when their minds are shrieking that they are not safe. Cognitive techniques help with reality-testing so that they can learn to recognize that the world is not as dangerous as their minds tell them it is. Along with defusing from thoughts of danger and using grounding and mindfulness techniques to increase their tolerance for the stimulation of day to day life, they need to be challenged to maneuver out in the world and try new things (people with CAPS can be notoriously stubborn!) so they can develop self-efficacy and a life with purpose. Without intervention, these people may be on the highway to developing secondary CAPS, and even chronic illness.
The older, often chronically ill, CAPS folks with established PTSD wiring need help managing dissociative symptoms, dysautonomia, constant thoughts/feelings of dread/shame/fear with little current basis for them, withdrawal/social isolation, in addition to managing the exaggerated acute stress response which is draining what’s left of their mojo. They also need help with changing energy-draining and no longer effective habits (again, stubbornness!), as well processing losses associated with illness. This can be done with self-help books alone, but it is much easier to do this with professional help.
Final Word: I hope that this section has been helpful for everyone. I believe that the discovery of CAPS and its association with the RCCX Module and chronic medical and psychiatric illness is very important. Please share this website widely, talk about it in your blogs and in your support groups.
Again, what I have written here is a road map. We don't have definitive evidence that CAPS is due to CYP21A2 mutations. I also can not make treatment recommendations on a website. It is vital that you discuss all of the above with doctors/therapists before engaging in an attempt to heal yourself. If you find this helpful, please feel free to share this widely. So much more help will be on the way, if we can prove that CYP21A2 mutations are involved in mental health and chronic illness. We need to have this possibility recognized and then I believe that we will have scientists interested in pursuing this with Karen Herbst MD PhD and I (see below).