Recognizing the Pattern
There's a sweet spot of arousal where we have focus, motivation, and energy. On one side of it is low arousal — brain fog, low motivation, low energy, something that can look a lot like ADD in both children and adults. On the other side is hyper-arousal — when we have excessive focus and drive, often accompanied by physiological stress.

Many of the people I see fluctuate between both ends and struggle to find that middle place. They tend to have deep interests. They can become intensely interested in something, even obsessive about it, and can have difficulty disengaging. When there is not enough stimulation, they tend to get bored easily. They often don't enjoy small talk.

What Arousal Means Physiologically
When I say arousal, I mean a state in which our body and brain are ready to act. This requires cortisol, along with catecholamines like norepinephrine (motivation) and dopamine (focus). If we have low arousal, it can be hard to mobilize focus, motivation, or energy. Imagine you are feeling tired and sluggish and then you get a call about an urgent matter. Suddenly, you are alert and ready to act. When necessary our level of arousal can shift on a dime. Our survival depends on it.

The RCCX Connection
The best explanation I've found for why some of us find ourselves at either end of the arousal spectrum and not easily in the middle sweet spot, is RCCX theory, developed by Dr. Sharon Meglathery. RCCX refers to the gene module that holds a gene involved in hypermobility, the gene for 21-hydroxylase — an enzyme essential to the hormone pathway that produces cortisol, and a gene tied to autoimmunity. You don't need all of these affected for RCCX to be relevant to you; from a psychiatric and brain-symptom standpoint, 21-hydroxylase is the one that matters most.

An estimated 20% of people may carry some variant on this gene. It isn't something we can currently pin to a single variant; there are likely many loci on this gene that could cause this enzyme to be "slow" or "fast." A weakness could result in someone with a lower baseline cortisol. Under stress, they can produce enough cortisol, until that enzyme gets overwhelmed and can't keep up with the demand.

This same genetic vulnerability could also impact the developing brain in early life, something I've discussed in previous newsletters about RCCX theory. Low basal cortisol along with higher androgens (from a backup in hormonal pathways so to speak) and spiking cortisol levels (when under stress) can affect areas including the amygdala, which senses threat. That may explain why these individuals can also be gifted, struggle with anxiety and struggle to put the brakes on once they're engaged in something.

The Crash — and Why It Happens
When the enzyme can no longer meet the demand, cortisol and those neurotransmitters drop. That's the crash: low energy, poor focus, no motivation. For some people, hitting that wall also triggers mast cell activation. Corticotropin releasing hormone or CRH (the brain's signal asking the adrenals for more cortisol) can bind to mast cells, which can then release histamine and inflammatory mediators, resulting in worsening fatigue, brain fog, and physical symptoms.

This isn't only about a single hard day. Zoom out, and I've seen people who were high-functioning — even hyper-functioning — for years, doing remarkable things across work, family, and adventure, before hitting a wall they never fully recovered from. Often there's something else quietly using up their stress capacity underneath it all: mold or biotoxin exposure, mitochondrial dysfunction, a chronically stressful relationship, early attachment disruption, or even codependent relationship patterns that keep someone chronically stressed.

Once someone is in that low-arousal state, it's common to unconsciously reach for something to bump arousal back up — carbs, internet scrolling, risk-taking, even calling the one person in their life who reliably brings drama. These aren't failures of willpower. They're the nervous system trying to get back to a state that feels more functional. There are other ways to do this.

Finding the Sweet Spot
The starting point is simply noticing. Notice when you're in that low-arousal state and what you reach for. Notice when you're in a hyper-aroused state — often visible in tight muscles around the neck and shoulders, or an inability to stop and take a break even when you know you should.

For High Arousal
Take real breaks, even when it's the last thing you want to do. Alternate high-intensity work with low-intensity work. Chunk projects into smaller pieces with defined stopping points instead of letting a project sprawl endlessly. Set an intention — how long you'll work before a break — before you start.

For Low Arousal
Change your setting, or find a way to make the task more meaningful or creative. Movement helps raise arousal. A timer or a defined challenge can help too — a bit of urgency, used well, can bump focus and motivation without tipping into overload.
None of this is one-size-fits-all. What works will be different for each of us. But understanding our own arousal pattern — rather than labeling it as inconsistency, self-sabotage, or a self-esteem problem — is often the first real step off the roller coaster and toward being able to use the gifts we already have.
I'd love to hear your thoughts and experience. Have you found things that help you find your own sweet spot?
If you'd like these newsletters and episodes delivered to your inbox each week, subscribe at CourtneySnyderMD.com, where you'll also find information on consultations and treatment.

Until next time,
Courtney

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 her YouTube Channel reaches readers and listeners in over 160 countries.

Resources
RCCX Theory & Psychiatry. Dr. Sharon Meglathery
RCCX Theory: Hypermobility, RCCX Theory, Mental Health & Complex Chronic Illness
Recent newsletter on Hypersensitivity: High Sensitivity Through 3 Lenses (HSP, Pyrrole Disorder & RCCX Theory)

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, and OH. Her educational content — shared through her website, Substack Newsletter, the Holistic Psychiatry Podcast, and her YouTube Channel — reaches readers and listeners in over 160 countries.

In my over twenty years as a psychiatrist, I've worked with thousands of children and adults who are highly sensitive. Most are deep divers into information, able to connect a lot of dots; many are gifted. And yet many also struggle with overwhelm, low stress tolerance, anxiety, or an inner tension that's been there for as long as they can remember.  Many feel different — like they don't quite fit in.
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What I've found, again and again, is that the sensitivity itself is rarely the problem. It's the vulnerability it seems to carry alongside it — to brain-related symptoms, to physical illness, to feeling perpetually at the edge of overwhelmed.

Over the years, I've found three different frameworks especially useful for explaining both the strengths and the vulnerabilities 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 cluster of traits through a different lens — psychological, biochemical, and genetic.

Before I get into it, I want to be clear about one thing: sensitivity is not a pathology or a diagnosis. It's a trait that has existed across human history for a reason. My goal isn't to pathologize it — it's to understand it, and to offer tools to the people who carry these traits and are also struggling with a condition that shows up more often in this population. As I walk through these three frameworks, you'll notice real overlap between them. I'll try to point out what each one offers that the others don't.

What You'll Learn

• How the HSP model offers validation and a language for sensitive people
• Why Pyrrole Disorder leads to depletion of nutrients essential for neurotransmitter function
• How Pyrrole Disorder shows up across brain-related conditions
• How RCCX Theory connects genetic vulnerability to sensitivity and chronic illness
• Why stress amplifies the experience across all three models
• How understanding these frameworks can point toward real treatment options
• Why there are meaningful, hopeful paths forward for highly sensitive people

I. THE HIGHLY SENSITIVE PERSON
In the early 1990s, psychologist Dr. Elaine Aron identified a personality trait she called Sensory Processing Sensitivity (SPS) — and named the people who score high in it Highly Sensitive Persons, or HSPs.

This is not a diagnosis. It's a trait, present in roughly 15–20% of the population, and it's been documented across more than 100 species, from fruit flies to primates. That tells us something: it's evolutionarily conserved, which means it confers a survival advantage. In any social group, having members wired to notice subtle cues, process information deeply, and detect threats before others do is genuinely valuable. Fittingly, many highly sensitive people who also struggle with complex chronic illness are the ones described as "canaries in the coal mine" — their bodies react to environmental toxins, chemicals, or stressors long before everyone else's does.

Dr. Aron summarized the trait with an acronym, DOES:

• D — Depth of processing. HSPs think deeply, reflect before acting, and notice subtleties others miss.
• O — Overstimulation. Because they're processing so thoroughly, HSPs hit their threshold faster in high-stimulation environments.
• E — Emotional reactivity and empathy. HSPs feel things intensely and are highly attuned to the emotions of people around them.
• S — Sensitivity to subtle stimuli. They pick up on things — in their environment, in social dynamics, in their own bodies — that others simply don't register.

Here's the thing about traits like these: the same wiring that makes someone a superpower can, under the wrong conditions, become a liability. The deep diver loses sight of the big picture. The empath absorbs everyone else's energy until her own is gone. The person who notices everything eventually withdraws because the world has become too loud.

HSP Research
Beyond clinical observation, there's a growing body of neuroscience and genetics behind this. fMRI studies (Acevedo, Aron, et al., 2014) found that when HSPs view emotionally meaningful images — especially photos of loved ones expressing happiness or sadness — their brains show significantly greater activation in regions tied to awareness, empathy, and sensory integration.

Twin studies estimate SPS is about 47% heritable. Smaller genetic studies point to variants involving dopamine and serotonin regulation — a serotonin transporter gene, a dopamine receptor gene, and COMT, the enzyme that metabolizes dopamine and norepinephrine. This hints at a biochemical layer, though the HSP model itself doesn't explain the mechanism directly, and it doesn't fully account for the higher rates of physical illness we see in this population.

Research published in 2026 (Matsuzawa et al.) found that people high in SPS had substantially higher rates of depression, anxiety, ADHD, and autism spectrum disorder than the general population. Despite that overlap, important distinctions remain — unlike ADHD, HSPs typically concentrate well in calm environments; unlike ASD, HSPs tend toward heightened social attunement, often perceiving too much social information rather than too little, even when they respond to it awkwardly. High SPS has also been linked to more frequent physical symptoms — fatigue, digestive complaints, frequent illness, musculoskeletal pain.

What This Framework Offers
The HSP model has given millions of people validation and a language that lets them move from "what's wrong with me" to "this is how I'm wired." It offers an evolutionary reframe: high sensitivity isn't a mistake, it's a feature. What it doesn't offer is a biological explanation for why some sensitive people suffer so acutely, or a path toward biochemical treatment. That's where the next two frameworks come in.

II. PYRROLE DISORDER
Pyrrole Disorder is a biochemical imbalance that's been recognized for decades, though it remains largely overlooked in mainstream psychiatry. It involves an overproduction of pyrroles — metabolic byproducts that are harmless on their own, but that bind to and deplete zinc, vitamin B6, and a few other important nutrients when levels run high.

First identified in the 1950s and treated with zinc and B6 starting in the 1980s, Pyrrole Disorder is one of the most common nutrient imbalances found in brain-related conditions — and one of the most responsive to treatment. And yet most people who have it have never heard of it. I was first introduced to pyrroles in 2014, training with the Walsh Research Institute.

Why Zinc, B6, and Magnesium Matter
Vitamin B6 is required to make dopamine, serotonin, and GABA — three neurotransmitters central to mood, anxiety, and stress resilience. Zinc supports the central nervous system, the immune system, the gastrointestinal tract (which we now know profoundly affects brain health), and connective tissue. Magnesium works alongside both in pathways tied to stress regulation and neurotransmitter activity.

Traits and Symptoms
The most consistent feature is low stress tolerance — everyday life feels harder than it seems to for other people, and ordinary transitions can feel destabilizing. The overlap with the HSP profile is striking, but here we start to see symptoms, not just traits: social anxiety or shyness since childhood with persistent inner tension; sensitivity to bright light, loud sound, texture, and odor; discomfort in crowds or new situations; a history of reading difficulty; poor short-term memory; underachievement relative to intelligence; irritability and mood swings; staying up late with little dream recall and morning nausea; white spots on the fingernails, dry skin, stretch marks, slow wound healing; joint pain; frequent infections or autoimmune tendencies. Not everyone has all of these — but the inner tension, the sensitivity, and the low stress tolerance are nearly universal.

What the Data Shows
The Walsh Research Institute has collected biochemical data on more than 30,000 patients. Elevated pyrroles turned up in 18% of those with ADHD, 24% with depression, 28% with behavioral disorders, 35% with autism, 35% with bipolar disorder, 30% with schizophrenia, and 12% with PTSD — compared to just 8% of healthy controls with no psychiatric diagnosis.

Cause
For some, there's a strong genetic component. For others, pyrroles seem to rise in response to prolonged physiologic or emotional stress — Candida overgrowth or other gut imbalances, mold toxicity, heavy metals, chemical exposure, illness, trauma, major life transitions, even growth spurts in children.

What This Framework Offers
Compared to the HSP model, Pyrrole Disorder gives us something specific and treatable. When zinc, B6, magnesium, and other nutrients are depleted, we understand how that shapes neurotransmitter function — and we have an evidence-based way to correct it. Treatment from a Walsh-trained practitioner typically means an individualized protocol — zinc guided by zinc and copper testing, B6 or its active form P5P, and other targeted nutrients. For many patients, chronic inner tension and fearfulness start to shift within days to a few weeks. Treatment doesn't erase someone's natural sensitivity — it lifts the anxiety, overwhelm, and depression that accumulated on top of it.

Zinc deficiency explains a lot, but it doesn't fully account for the hormonal, inflammatory, connective tissue, and autoimmune symptoms we also see in this population. That's where the third framework comes in.

III. RCCX THEORY
RCCX Theory was developed by Dr. Sharon Meglathery, MD — a psychiatrist and internist whose own complex health history, which closely parallels my own, led her to one of the most compelling explanations I've come across for why high sensitivity, neurodivergence, psychiatric conditions, and complex chronic illness — MCAS, EDS, POTS, CIRS, CFS, autoimmunity — so often travel together in the same people and the same families.

The RCCX module is a cluster of four genes on chromosome 6. Three matter most for our purposes, and two of those carry high mutation rates.

TNXB codes for a protein involved in connective tissue. Variants range from mild joint hypermobility to Ehlers-Danlos Syndrome. But connective tissue isn't only about joints — it also governs gut and blood-brain barrier permeability, and vulnerability to upper cervical instability, which can put tension on the vagus nerve and affect the entire autonomic nervous system.

CYP21A2 may be the most psychiatrically significant gene in the module. It codes for 21-hydroxylase, the enzyme that converts 17-hydroxyprogesterone into cortisol. Mutations here — and there are many, of varying severity — can leave the body unable to keep up with cortisol demand under stress. Dr. Meglathery proposes two consequences. First, people with CYP21A2 variants, even without hypermobility, may develop what she calls a "brain wired for danger" — a nervous system calibrated toward threat detection from early in life, often with very little trauma required. One theory: relatively higher androgen exposure during development affects the amygdala, the brain's fear center — and interestingly, hypermobile individuals, who often carry TNXB variants, have been found to have a larger-than-average amygdala. Second, when the body can't produce enough cortisol, the brain releases corticotropin-releasing hormone (CRH) to push the adrenals harder — but CRH also activates mast cells, triggering immune activation and inflammation. That inflammatory cascade can feed into MCAS, CIRS, POTS, CFS, and other conditions.

C4 is involved in immune regulation and autoimmunity, and has been linked to schizophrenia. It's less commonly mutated than the other two, though I regularly see families where autoimmune disease runs across multiple relatives.

The CAPS Psychological Profile
Dr. Meglathery uses the term CAPS — CYP21A2 Mutation Associated Neuropsychiatric Spectrum — to describe the profile she's observed clinically. These traits often exist well before any formal diagnosis, and they aren't inherently pathological: anxiety and over-arousal under stress (sometimes with manic-like features); under-arousal during quiet periods, which can look like ADD, compulsive behavior, or thrill-seeking; high emotionality and reactivity to environmental stimuli; sensory overwhelm in loud or chaotic settings; a strong read on other people's emotions paired with social awkwardness in response; being deeply affected by things others shrug off; nonconformity; real gifts in music, science, creativity, or systems thinking; hyperfocus that leads to real accomplishment; high tenacity when not derailed by overstimulation or past trauma; and strong emotions that can surface as worry, perfectionism, OCD tendencies, or very high standards for self and others.

Dr. Meglathery has also observed — and I've seen this clinically too — that people with this profile tend to find each other, through friendship, partnership, and marriage. They're drawn together by shared sensitivity, emotional depth, and intellectual curiosity, which means their children often inherit a double dose of CAPS-related tendencies. She also notes a physical marker: women who appear to carry CYP21A2 mutations often show a more male-typical finger-length ratio — ring finger longer than index — a possible sign of androgen exposure during development.

What RCCX Offers
Of the three frameworks, RCCX gives us the broadest biological explanation for why sensitivity, psychiatric vulnerability, and complex chronic illness cluster together — connecting the nervous system, immune system, hormones, and connective tissue under one genetic umbrella. It also points to interventions beyond traditional psychiatric care: nervous system regulation (limbic retraining, vagal work), mast cell support, hormonal balance, and addressing the downstream effects of cortisol dysregulation. The limitation is that comprehensive CYP21A2 testing isn't yet widely available clinically, which is part of why it's rarely discussed alongside HSP — even though I suspect it may be the most prevalent contributor of the three. RCCX remains an evolving clinical theory rather than an established consensus, but it's one of the most compelling explanations I've found for what I see, over and over, in practice.

IV. WHERE THESE MODELS INTERSECT
The overlap between Pyrrole Disorder and RCCX Theory is hard to miss — poor stress tolerance, sensory sensitivities, anxiety, inner tension, connective tissue symptoms, frequent infections, autoimmune tendencies. Relatively low zinc explains a lot of that shared symptom picture, but there may be a deeper connection still: 21-hydroxylase contains a heme structure with pyrrole-like characteristics. Could a mutation that disrupts 21-hydroxylase contribute to a buildup of heme-related compounds — and, in turn, to Pyrrole Disorder itself? That's a hypothesis, not a proven mechanism. But in a conversation I had with Dr. Meglathery, she told me she believes there's likely a real association, and the biochemical logic is compelling.

This matters because Pyrrole Disorder is one place where we already have a working treatment — one that can complement what RCCX Theory makes clear: that addressing the body's stress response is essential.

One theme runs through all three models: stress is the great amplifier. Whether it's emotional, physiological, environmental, infectious, or toxic in origin, stress intensifies the HSP experience, tips CYP21A2 vulnerability from manageable to destabilizing, and drives pyrrole production higher.

BRINGING IT ALL TOGETHER
For someone who is highly sensitive and also struggling with psychiatric symptoms, neurological concerns, or chronic physical illness, both Pyrrole Disorder and RCCX Theory are worth knowing about — because they move past "why" and start answering "what can we do about it."

The HSP model offers understanding, validation, and language. It reframes sensitivity as a trait with real evolutionary value, not a flaw.
The Pyrrole Disorder model offers a specific, treatable biochemical mechanism — one that explains, at the neurotransmitter level, why stress lands so much harder for some people. Treatment doesn't remove someone's sensitivity; it lifts the anxiety and overwhelm layered on top of it.

The RCCX model offers the broadest systems view — connecting nervous system regulation, immune function, hormonal balance, and connective tissue health into one framework, and opening up treatment options beyond conventional psychiatric care.

Each model contributes something the others don't. Together, they offer a fuller picture of why some people experience the world so intensely — and why that intensity can, at times, become a source of real suffering.

If you recognize yourself in any of this — the heightened sensitivity, the lifelong inner tension, the low stress tolerance, or the sense of constantly living at the edge of overwhelm — please know there are roots here worth exploring, and real paths forward.

Resources

• Walsh Research Institute (biochemical data on 30,000+ people with brain-related symptoms): walshinstitute.org
• RCCX Theory — Dr. Sharon Meglathery: rccxandillness.com
• Dr. Elaine Aron — The Highly Sensitive Person: hsperson.com
• Acevedo BP, Aron EN, Aron A, et al. (2014). "The Highly Sensitive Brain: An fMRI Study of Sensory Processing Sensitivity and Response to Others' Emotions." Brain and Behavior.
• Matsuzawa R, et al. (2026). "Relationships Among Highly Sensitive Personality (HSP), Neuroticism, Mental Health, Neurodevelopmental Traits, and Adverse Childhood Experiences (ACEs)." Psychiatry and Clinical Neurosciences Reports.

Medical Disclaimer: This post is for educational purposes and is not intended or implied to be a substitute for professional medical advice, diagnosis, or treatment for yourself or others, including patients you may be treating if you are a practitioner. Consult your own physician for any medical issues you may be having.

​Mast cells are first responders in the immune response. When they are highly reactive and destabilize, they release inflammatory mediators that cause abrupt symptoms like hives, wheezing in someone with asthma or even anaphylaxis in someone with a food allergy. Though not in the brain, they communicate with inflammatory cells in the brain and can cause abrupt symptoms, including panic attacks.

​What Does Panic Feel Like? & Why Is This Happening?

​In response to the person who asked me to talk about symptoms of mold toxicity in children.

​Someone asked, “How do you test for mold toxicity?”

​How does not having our head on straight impact our mental health?