As a holistic and functional psychiatrist, I see many people who are highly sensitive. Most are deep divers into information and able to connect a lot of dots. Many are gifted. Many struggle with overwhelm and low stress tolerance. Some struggled with anxiety, inner tension, or feeling “too much” for as long as they can remember. Some feel different - that they don’t fit in.
As a holistic and functional psychiatrist with over twenty years in practice, I've worked with thousands of highly sensitive adults and children. Most are deep divers into information, able to connect a lot of dots — many are gifted. And yet many struggle with overwhelm, low stress tolerance, anxiety, or inner tension that has been there for as long as they can remember. Many feel different, like they don't quite fit in. What I've found is that sensitivity itself is rarely the problem — it’s the seeming vulnerability to brain-related or physical conditions.
Over the years I’ve found three different models to be especially useful in explaining some of the vulnerabilities and the strengths of those of us who are highly sensitive: Dr. Elaine Aron’s work on the Highly Sensitive Person (HSP), the nutritional medicine concept of Pyrrole Disorder, and Dr. Sharon Meglathery’s RCCX Theory. Each looks at a similar group of traits through a different lens — psychological, biochemical, and genetic, respectively.
Before I start, I want to emphasize that sensitivity is not a pathology or a diagnosis. It is actually a trait that has existed across human history for a reason. My goal is not to pathologize it, but to understand it — and to offer tools to those who have these traits but who are struggling with a condition more prevalent in those with these traits. As I go through these three frameworks, the overlap will be obvious and I’ll highlight what each of these has to offer that the others don’t.
What You'll Learn
* The HSP model provides validation and a language for sensitive individuals.
* Pyrrole Disorder involves an overproduction of pyrroles, leading to nutrient depletion of nutrients critical for neurotransmitter functioning.
* Pyrrole Disorder is common in brain-related conditions.
* RCCX Theory connects genetic vulnerabilities to sensitivity and chronic illness.
* Stress amplifies the experiences of highly sensitive individuals.
* Understanding these models can lead to effective treatment options.
* There are meaningful paths forward for those who are highly sensitive.
Chapters
* 00:00 Understanding High Sensitivity
* 02:26 The Highly Sensitive Person (HSP) Model
* 10:23 Exploring Pyrrole Disorder
* 18:18 RCCX Theory Explained
* 30:11 Intersecting Models: HSP, Pyrrole Disorder & RCCX Theory
* 34:40 Conclusion and Path Forward
I. THE HIGHLY SENSITIVE PERSON
In the early 1990s, psychologist Dr. Elaine Aron identified a personality trait she called Sensory Processing Sensitivity (SPS) — and the people who score high in it she called Highly Sensitive Persons, or HSPs.
This is not a diagnosis. It is a trait, present in roughly 15–20% of the population. It has been found across more than 100 species — from fruit flies to primates. This tells us it is evolutionarily conserved — it confers survival advantages. In any social group, having members who are wired to notice subtle cues, process information deeply, and detect threats before others do is extremely valuable. Fitting with this, many of these individuals, who also struggle with complex chronic health issues are considered the “canaries in the coal mine” since their bodies react to environmental triggers (environmental toxins, chemicals, or stressors) long before the rest of the population.
Dr. Aron captured the core features of this trait in an acronym she called DOES:
D — Depth of processing: HSPs think deeply, reflect before acting, and notice subtleties that others miss.
O — Overstimulation: Because they process so thoroughly, HSPs reach their threshold more quickly in high-stimulation environments.
E — Emotional reactivity and Empathy: HSPs feel emotions intensely and are highly attuned to the emotions of those around them.
S — Sensitivity to subtle stimuli: They pick up on things — in their environment, in social dynamics, in the body — that others simply don’t register.
As you can see, traits that are super powers, can become liabilities. The deep diver who loses sight of the big picture. The empath who absorbs everyone else’s energy as their own energy becomes depleted. The person who withdraws from the world because the stimulation has simply become too much.
HSP Research
Beyond the clinical observations, there is now a growing body of neuroscience and genetic research supporting this trait. There is evidence that the brains of sensitive people are doing more, processing more and feeling more.
fMRI studies (Acevedo, Aron et al., 2014) have shown that when HSPs view emotional images — particularly photos of loved ones expressing happiness or sadness — their brains show significantly greater activation in regions associated with awareness, empathy, and sensory integration.
Twin studies show that Sensory Processing Sensitivity (SPS) as defined by Dr. Aron is approximately 47% heritable. Small studies as opposed to large genome wide studies have focused on genetic variants involving dopamine and serotonin systems, such as a serotonin transport gene, a dopamine receptor gene, and COMT, which codes for the enzyme that metabolizes dopamine and norepinephrine.
While this hints at a biochemical dimension, the HSP framework doesn’t address this as directly as the other two models I’ll discuss, nor does it explain the higher prevalence of physical health conditions in those who are highly sensitive.
Research published in 2026 (Matsuzawa et al.) found that individuals high in SPS had substantially higher rates of depression (13.8%), anxiety disorder (10.5%), and developmental disorders, such as ADHD and ASD, compared to the general population.
Despite this overlap with developmental disorders: unlike, ADHD, HSPs typically have excellent concentration in quiet environments. And unlike the social deficits described in ASD, HSPs tend to have heightened social attunement. They often feel too much of what’s happening in social situations, not too little, even if they respond awkwardly at times.
Research shows that high sensory processing sensitivity is associated with more frequent physical symptoms — back pain, fatigue, digestive issues, frequent illness.
What This Framework Offers
The HSP model has given millions of people validation and a language for these traits that has allowed them to shift from “what is wrong with me” to “this is how I am wired.”
It also offers an evolutionary reframe. High sensitivity is not a mistake and is not pathologic. It is a feature of the human population that has served us.
What it doesn’t offer is a biological explanation for why some sensitive people suffer so acutely — or a path toward biochemical intervention.
II. PYRROLE DISORDER
Pyrrole disorder is a biochemical imbalance that has been recognized for decades, though it remains largely unknown in mainstream psychiatry. It involves an overproduction of pyrroles — metabolic byproducts that, on their own, are not a problem. When they are high, however, they can result in a depletion of zinc, B6 and a few other nutrients.
First identified in the 1950s and first treated with zinc and B6 in the 1980s, pyrrole disorder is one of the most common nutrient imbalances found in brain-related conditions — and one of the most treatable. Yet most people who have it have never heard of it. I learned about pyrroles in 2014 when I first trained with the Walsh Research Institute.
The Importance of Zinc, B6 & Magnesium
Vitamin B6 is required to synthesize dopamine, serotonin, and GABA — three of the most critical neurotransmitters for mood regulation, anxiety, and stress response. Zinc plays a profound role in the central nervous system, the immune system, gastrointestinal tract (which we now know has its own significant influence on brain health) and connective tissue (joints and skin).
Pyrrole Disorder Traits & Symptoms
The most consistent feature is low stress tolerance. People with elevated pyrroles are often described as those for whom life seems harder than it should be, every transition can be destabilizing and every large group or new environment feels like too much.
The overlap with the HSP profile is striking, but here, we start to see not only traits, but symptoms.
- Socially anxious, shy, or fearful since childhood, with severe inner tension
- Sensitive to bright light, loud noises, textures, and odors
- Avoids crowds, strangers, and new situations
- History of reading difficulty
- Poor short-term memory
- Underachievement
- Irritability, mood swings, bouts of depression
- Tends to stay up late; little or no dream recall; morning nausea
- White spots on fingernails; very dry skin; stretch marks; poor wound healing
- Joint pain
- Frequent infections or autoimmune tendencies
Most people with pyrrole disorder don’t have all of these symptoms — but the inner tension, the high sensitivity, and low stress intolerance are very common.
What the Data Shows
The Walsh Research Institute has collected data on over 30,000 patients. Elevated pyrroles were found in:
* 18% of those with ADHD
* 24% of those with depression
* 28% of those with behavioral disorders
* 35% of those with autism
* 35% of those with bipolar disorder
* 30% of those with schizophrenia
* 12% of those with PTSD
And in only 8% of healthy controls — meaning those with no psychiatric diagnosis.
What Causes Pyrrole Disorder?
For many, there appears to be a genetic component, but for others, pyrroles appear to have increased due to high physiologic or emotional stress. Examples include candida overgrowth or other forms of gut microbial imbalances, mold toxicity, heavy metals, chemical exposures, illness, emotional trauma, major life transitions or even growth spurts in children.
What This Framework Brings Us
Relative to the HSP framework, an understanding of pyrroles gives a specific, treatable biological mechanism. When zinc, B6, Magnesium and other nutrients are depleted, we know how the brain’s neurotransmitter functioning is affected — and we know what to do about it.
Treatment from a Walsh Research Institute trained practitioner typically involves a nutrient protocol of zinc (based on zinc and copper testing), B6 or its active form P5P, and other nutrients for pyrrole disorder and other nutrient imbalances identified. For many patients, a lifetime of chronic inner tension and fearfulness begins to shift within days to a couple of weeks of starting the nutrients.
Treatment doesn’t change one’s personality, but it can improve social discomfort, overwhelm, the anxiety, the depression that has been layered on top of that sensitivity.
Where zinc deficiency can impact a lot of the physical conditions that appear to be more common in those who are hypersensitive, it doesn’t fully explain the significant hormonal, inflammatory, connective tissue symptoms and autoimmunity we see in many who are hypersensitive.
III. RCCX THEORY
RCCX theory has been proposed by Dr. Sharon Meglathery, MD — a psychiatrist and internist whose own complex health history (which is very similar to my own) led her to one of the most compelling explanations I’ve encountered for why hypersensitivity, neurodivergence, psychiatric conditions, MCAS (Mast Cell Activation Syndrome), EDS (Ehlers Danlos Syndrome), POTS (Postural Orthostatic Tachycardia Syndrome), CIRS (Chronic Inflammatory Response Syndrome) and/or CFS (Chronic Fatigue Syndrome) and autoimmunity tend to cluster together in certain individuals and families.
RCCX refers to a module of four genes on chromosome 6. Three of them appear to be particularly important to our health, and two of those have very high rates of mutation.
The Three Key Genes
(1) TNXB codes for a protein involved in connective tissue. Variants range from subtle joint hypermobility to Ehlers-Danlos Syndrome. But connective tissue isn’t just about joints — it’s also about the permeability of the gut-blood barrier, the blood-brain barrier, and vulnerability to upper cervical (neck) instability, which can put tension on the vagus nerve and affect the entire autonomic nervous system.
(2) CYP21A2 is the most important gene in the module when it comes to psychiatric conditions. It codes for 21-hydroxylase, an enzyme needed to convert 17-hydroxyprogesterone into cortisol. When there is a mutation — and there can be many, of varying degrees — the body may struggle to meet the demand for cortisol under stress. A weakness on this gene could have two primary effects:
First — The theory holds that many people with CYP21A2 mutations, even without hypermobility, may develop what Dr. Meglathery calls a “brain wired for danger” — essentially, a nervous system calibrated toward threat detection from early in life, with minimal trauma required. A mutation on CYP21A2 may essentially result in relatively higher androgens impacting the amygdala — the brain’s fear and emotional center. Studies have found that hypermobile individuals (who often carry TNXB mutations) have a larger-than-normal amygdala.
Second — because of this mutation, the body may not be able to keep up with the body’s need for cortisol (especially when under stress). This deficit causes the brain to release corticotropin releasing hormone (CRH) to signal the adrenal glands to produce more cortisol. CRH binds to mast cells and activates the immune system — leading to secondary brain inflammation. This is the inflammatory pathway that can result in a number of secondary health issues including MCAS, CIRS, POTS, CFS and more.
(3) C4 is involved in immune response and autoimmunity, and has been linked to schizophrenia. This gene variant is not as common as the first two referenced, though I do see a number of families who also have autoimmunity impacting multiple family members.
The CAPS Psychological Profile
Dr. Meglathery uses the term CAPS — CYP21A2 Mutation Associated Neuropsychiatric Spectrum — to describe the psychological profile she has observed in people with this genetic vulnerability. These traits can exist long before any formal psychiatric diagnosis, and they are not inherently pathological.
- Anxiety and over-arousal during times of stress — high adrenaline, insomnia, sometimes manic-like characteristics
- Under-arousal during low-stress periods — leading to ADD presentations, compulsive behaviors, or thrill-seeking to raise arousal
- High emotionality, sensitivity, and reactivity to environmental stimuli
- Sensory processing difficulties — typically over-stimulation in loud or chaotic environments
- A strong ability to read emotions in others, paired with social awkwardness in response
- Easily affected by events others would consider minor — an offhand comment, a disturbing movie
- A tendency toward nonconformity
- Special abilities: gifted musicians, scientists, creatives, systems thinkers
- Hyper-focus and obsession with areas of deep interest, often leading to remarkable accomplishments
- High tenacity and determination, when not derailed by overstimulation or past trauma
- Strong emotions — positive or negative — that can manifest as obsessional worrying, harm avoidance, OCD tendencies, or very high standards for self and others
Dr. Meglathery also notes — and I have observed this clinically — that people with this profile tend to find each other through friendships, partnerships and marriage. They are drawn together by shared sensitivities, emotional depth, and intellectual gifts. This means children are likely to receive a tendency towards CAPS from both sides.
Women who are appear to have CYP21A2 mutations often have a male-pattern finger length ratio — the ring finger longer than the index finger — a possible marker of androgen exposure during development.
What RCCX Offers
RCCX theory offers the broadest biological framework we have for understanding why sensitivity, psychiatric vulnerability, and complex chronic illness so often travel together in the same people and families. It connects the nervous system, the immune system, the hormonal system, and connective tissue under one genetic umbrella.
It also points toward specific interventions: nervous system regulation (limbic retraining, vagal work), mast cell management, and addressing the downstream biochemical consequences of cortisol dysregulation.
The limitation is that genetic testing for variants on the gene for 21-hydroxylase is not yet widely available, which is why this isn’t a gene that you’ll see referenced when it comes to HSP, though I would argue it is likely the most prevalent. RCCX remains a clinical theory — but one that explains the constellation of traits and symptoms of most of the people that I in my practice
IV. WHERE THESE MODELS INTERSECT
Where Might Pyrrole Disorder and RCCX Theory Meet?
The symptom overlap is almost complete: poor stress tolerance, sensory sensitivities, anxiety, inner tension, connective tissue symptoms, frequent infections, autoimmune tendencies. Relatively low zinc would impact most of these shared symptoms, but there may be a potentially deeper connection.
21-hydroxylase contains a pyrrole-like structure — heme — within it. Could a mutation resulting in abnormal 21-hydroxylase lead to a buildup of abnormal heme-like compounds, contributing directly to pyrrole disorder? This is not proven, but in an exchange about this with Dr. Meglathery, she indicated that she also believes there is a strong association, and the biochemical logic is compelling.
This matters, because we know what helps pyrrole disorder. We have a treatment — treatment that can complement what RCCX theory makes evident — that the stress response has to be addressed.
Stress (again from any cause - physiologic or emotional) is the great amplifier across all three models. Stress worsens the HSP experience, and tips the CYP21A2 mutation from manageable to destabilizing (through the hormonal consequences and the inflammatory cascade) and yes, it even causes pyrroles to increase.
BRINGING IT TOGETHER
For someone who is highly sensitive, and struggling with brain related or physical symptoms or conditions, pyrrole disorder and even RCCX theory are worth considering because they offer tools and start to answer, “What Can We Do About It?”
The three frameworks work together:
The HSP model offers validation and language. It shifts the frame from deficit to difference. It reminds us that sensitivity is not pathology — it is a trait with evolutionary value, and it comes with great strengths.
The Pyrrole model offers a treatable nutrient imbalance. It explains, at the neurotransmitter level, why stress hits harder for these individuals. Treatment doesn’t take away the sensitivity; it lifts the weight that has accumulated on top of it.
The RCCX model offers the broadest systems view. It connects the dots between what the body is doing — the immune activation, the hormonal dysregulation, the connective tissue involvement — and the psychiatric and psychological profile that tends to accompany it. It also provides additional tools: nervous system regulation, mast cell support, hormonal awareness.
If any of this resonates — the sensitivity, the inner tension, the feeling of always being at the edge of overwhelm — please know that there are roots to explore and meaningful paths forward.
If you are looking for someone trained by the Walsh Research Institute knowledgeable in assessing for and treating pyrrole disorder (and other common nutrient imbalances impacting brain health), or learning more about Dr. Aron’s work on HSP and Dr. Meglathery’s RCCX theory, I am providing those links below.
And as always, I welcome your thoughts, experience and questions.
Until next time,
Courtney
About the Author
Dr. Courtney Snyder MD is a Holistic and Functional Child and Adult Psychiatrist who offers non-patient consultations to individuals and practitioners nationally and internationally in addition to her treatment practice serving FL, IN, KY, OH. Her educational content, shared through her website, Substack Newsletter, the Holistic Psychiatry Podcast and YouTube Channel reaches readers and listeners in over 160 countries.
Resources
Walsh Research Institute: walshinstitute.org
RCCX Theory — Dr. Sharon Meglathery: rccxandillness.com
Dr. Elaine Aron — The Highly Sensitive Person: hsperson.com
Other Sources: Acevedo et al. 2014, “The Highly Sensitive Brain,” Brain & Behavior | Matsuzawa et al. 2026, Psychiatry & Clinical Neurosciences Reports
Medical Disclaimer:
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