High Sensitivity Through 3 Lenses: The Highly Sensitive Person, Pyrrole Disorder & RCCX Theory6/29/2026 
Courtney Snyder MD is a Holistic and Functional Child and Adult Psychiatrist. She 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 thirty years as a psychiatrist, I've worked with with thousands of individuals who identify as highly sensitive. They are often naturally curious, think deeply, and have an exceptional ability to recognize patterns and connect seemingly unrelated ideas. Many are intellectually gifted. At the same time, they frequently struggle with overwhelm, low stress tolerance, anxiety, persistent inner tension, or the lifelong feeling that they are somehow "different" or don't quite fit in. Over the years, I've found three frameworks to be especially valuable in helping explain both the unique strengths and the vulnerabilities commonly seen in highly sensitive individuals. These include 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. While each approaches sensitivity from a different perspective—psychological, biochemical, and genetic—they describe many of the same characteristics from complementary viewpoints. Before exploring these models, I'd like to emphasize one important point: high sensitivity is not a psychiatric diagnosis or a disease. It is a naturally occurring trait that has likely served an important evolutionary purpose throughout human history. My goal is not to pathologize sensitivity, but rather to better understand it—and to offer practical tools for individuals whose sensitivity is accompanied by mental health or physical conditions that occur more commonly within this population. As we move through these three frameworks, you'll notice considerable overlap, along with the unique contributions each model provides. What You'll Learn
Chapters 00:00 — Understanding High Sensitivity 02:26 — The Highly Sensitive Person (HSP) Model 10:23 — Understanding Pyrrole Disorder 18:18 — RCCX Theory Explained 30:11 — Where HSP, Pyrrole Disorder & RCCX Theory Overlap 34:40 — Final Thoughts & Moving Forward
I. THE HIGHLY SENSITIVE PERSON - A FRAMEWORK FOR UNDERSTANDING SENSITIVITY
In the early 1990s, psychologist Dr. Elaine Aron introduced the concept of Sensory Processing Sensitivity (SPS) and coined the term Highly Sensitive Person (HSP) to describe individuals who naturally score high in this trait. Being highly sensitive is not a medical or psychiatric diagnosis. Rather, it is a normal personality trait found in approximately 15–20% of the population. Researchers have also identified similar traits in more than 100 different animal species, from insects to primates, suggesting that sensitivity has been preserved throughout evolution because it offers important survival advantages. Within any community, individuals who naturally notice subtle environmental cues, process information more deeply, and detect potential threats earlier than others play an important role. Consistent with this, many highly sensitive individuals—particularly those who also develop complex chronic illnesses—are often described as the "canaries in the coal mine." Their nervous systems and bodies frequently respond to environmental toxins, chemicals, infections, and stressors long before these same exposures affect the broader population. Dr. Aron summarized the defining characteristics of Sensory Processing Sensitivity using the acronym DOES:
One of the fascinating aspects of this trait is that many of its greatest strengths can also become its greatest challenges. The deep thinker may become so immersed in details that the larger picture is temporarily lost. The empath may absorb the emotional burdens of others until their own energy is depleted. Someone who thrives on noticing everything may eventually withdraw simply because daily life has become overwhelmingly stimulating. HSP Research Beyond clinical observation, an expanding body of neuroscience and genetic research supports the existence of Sensory Processing Sensitivity. Studies suggest that highly sensitive individuals are not simply "more emotional"—their brains genuinely process information differently. Functional MRI studies (Acevedo, Aron et al., 2014) demonstrated that when HSPs viewed emotionally meaningful images—particularly photographs of loved ones expressing happiness or sadness—they showed significantly greater activation in brain regions involved in awareness, empathy, and sensory integration. Twin studies estimate that Sensory Processing Sensitivity is approximately 47% heritable. Smaller genetic studies have also identified associations with genes involved in dopamine and serotonin regulation, including the serotonin transporter gene, dopamine receptor genes, and COMT, the enzyme responsible for metabolizing dopamine and norepinephrine. These findings suggest a biological component to sensitivity, although the HSP model itself does not fully explain the underlying biochemical mechanisms or why highly sensitive individuals often experience higher rates of physical illness. Research published by Matsuzawa and colleagues (2026) found that individuals with high Sensory Processing Sensitivity experienced significantly higher rates of depression, anxiety disorders, ADHD, and autism spectrum disorder than the general population. Despite some overlap with neurodevelopmental conditions, important distinctions remain. Unlike many individuals with ADHD, HSPs generally maintain excellent concentration in calm environments. Likewise, unlike autism spectrum disorder, HSPs usually demonstrate heightened awareness of social and emotional cues—they often perceive too much social information rather than too little, even if responding to it can sometimes feel overwhelming. Additional research has also linked high sensory processing sensitivity with a greater frequency of physical symptoms, including fatigue, digestive complaints, frequent illness, musculoskeletal pain, and other chronic health concerns. II. PYRROLE DISORDER Pyrrole Disorder is a biochemical imbalance that has been recognized for decades, although it remains largely overlooked in conventional psychiatry. It is characterized by an overproduction of compounds called pyrroles—natural metabolic byproducts that are harmless at normal levels. When pyrroles become elevated, however, they bind to and deplete essential nutrients, most notably zinc and vitamin B6, along with several other nutrients important for healthy brain function. Originally identified in the 1950s, Pyrrole Disorder began to be treated with zinc and vitamin B6 in the 1980s. Today, it is recognized as one of the most common nutrient imbalances associated with brain-related conditions—and one of the most responsive to targeted nutritional treatment. Yet despite this, many people living with Pyrrole Disorder have never heard of it. I was first introduced to pyrroles in 2014 during my training with the Walsh Research Institute. The Importance of Zinc, Vitamin B6 & Magnesium The nutrients depleted in Pyrrole Disorder play critical roles throughout the brain and body. Vitamin B6 is required for the production of several major neurotransmitters, including dopamine, serotonin, and GABA—all of which influence mood regulation, anxiety, resilience to stress, and emotional well-being. Zinc is equally important. It supports healthy function within the central nervous system, immune system, gastrointestinal tract—which we now recognize as having profound effects on brain health—as well as connective tissue, including the joints and skin. Magnesium also contributes to healthy nervous system function and works alongside zinc and vitamin B6 in many biochemical pathways involved in stress regulation and neurotransmitter activity. Pyrrole Disorder Traits & Symptoms One of the defining characteristics of Pyrrole Disorder is poor stress tolerance. Individuals with elevated pyrroles often describe everyday life as feeling more difficult than it seems for others. Even relatively ordinary life changes may feel destabilizing, while crowded environments or unfamiliar situations can quickly become overwhelming. The similarities between Pyrrole Disorder and the Highly Sensitive Person profile are remarkable. The difference is that Pyrrole Disorder helps explain not only personality traits, but also the biochemical mechanisms contributing to symptoms. Common features include:
Not every individual with Pyrrole Disorder experiences all of these features. However, persistent inner tension, heightened sensitivity, and low stress tolerance are among the most commonly reported symptoms. What the Data Shows According to biochemical data collected by the Walsh Research Institute from more than 30,000 patients, elevated pyrroles have been identified in:
By comparison, elevated pyrroles were found in only 8% of healthy individuals without a psychiatric diagnosis. These findings suggest that Pyrrole Disorder occurs far more frequently in individuals with mental health conditions than in the general population. What Causes Pyrrole Disorder? For some people, Pyrrole Disorder appears to have a strong genetic component. For others, elevated pyrroles seem to develop in response to prolonged physiological or emotional stress. Potential contributing factors include:
Each of these factors may increase oxidative stress within the body, potentially contributing to higher pyrrole production and greater depletion of key nutrients. What This Framework Adds Compared with the Highly Sensitive Person model, Pyrrole Disorder offers something particularly valuable—a specific biological mechanism that can often be addressed through treatment. When zinc, vitamin B6, magnesium, and other nutrients become depleted, we understand how these deficiencies influence neurotransmitter production and nervous system function. More importantly, we have evidence-based strategies for correcting them. Treatment provided by a Walsh Research Institute-trained practitioner generally includes an individualized nutrient protocol that may involve zinc (guided by zinc and copper testing), vitamin B6 or its active form P5P, along with other nutrients selected according to the individual's biochemical profile. For many patients, symptoms such as chronic inner tension, excessive fearfulness, and low stress tolerance begin to improve within days to a few weeks after starting appropriate nutritional therapy. Importantly, treatment does not eliminate a person's natural sensitivity or fundamentally change their personality. Rather, it often reduces the anxiety, overwhelm, depression, and social discomfort that have accumulated on top of an already sensitive nervous system. Although zinc deficiency helps explain many of the neurological and physical symptoms commonly seen in highly sensitive individuals, it does not fully account for the hormonal changes, inflammatory processes, connective tissue abnormalities, or autoimmune conditions that also appear more frequently in this population. This is where RCCX Theory provides another important piece of the puzzle. III. RCCX THEORY RCCX Theory, developed by Dr. Sharon Meglathery, MD, offers one of the most comprehensive explanations I've encountered for why high sensitivity, neurodivergence, psychiatric conditions, and complex chronic illnesses so often occur together within the same individuals and families. Dr. Meglathery is both a psychiatrist and an internist whose own complex medical history—which closely parallels my own—led her to investigate the biological links between these seemingly unrelated conditions. Her work brings together psychiatry, genetics, endocrinology, immunology, and connective tissue disorders into a single, integrated framework. According to RCCX Theory, individuals who are highly sensitive may also be more likely to experience conditions such as MCAS (Mast Cell Activation Syndrome), Ehlers-Danlos Syndrome (EDS), POTS (Postural Orthostatic Tachycardia Syndrome), CIRS (Chronic Inflammatory Response Syndrome), Chronic Fatigue Syndrome (CFS), autoimmune disorders, and a variety of psychiatric conditions. Rather than viewing these diagnoses as unrelated, RCCX Theory suggests they may share common genetic roots. What Is the RCCX Module? The RCCX module refers to a cluster of four genes located on chromosome 6. Three of these genes appear particularly important in relation to human health, and two are known to have relatively high mutation rates. These genetic variations may help explain why certain individuals develop both psychological and physical symptoms that appear interconnected rather than independent. The Three Key Genes 1. TNXB. The TNXB gene produces a protein that plays an essential role in connective tissue. Variations in this gene can contribute to a spectrum of connective tissue differences, ranging from mild joint hypermobility to Ehlers-Danlos Syndrome (EDS). However, connective tissue extends well beyond joints and ligaments. It also influences the integrity of the gut barrier, the blood-brain barrier, and structural support throughout the body. Variants affecting TNXB may therefore contribute to increased intestinal permeability, altered blood-brain barrier function, and upper cervical instability, all of which can influence nervous system regulation through effects on the vagus nerve and autonomic nervous system. 2. CYP21A2. From a psychiatric perspective, CYP21A2 may be the most significant gene within the RCCX module. This gene encodes 21-hydroxylase, an enzyme responsible for converting 17-hydroxyprogesterone into cortisol, one of the body's primary stress hormones. Numerous mutations of varying severity have been identified within CYP21A2. Even relatively mild variations may reduce the body's ability to produce adequate cortisol during periods of increased stress. Dr. Meglathery proposes that this can influence mental and physical health in two important ways. A Nervous System Primed for Threat DetectionThe first involves the way the brain processes danger. According to RCCX Theory, individuals carrying CYP21A2 variants—even those without obvious connective tissue abnormalities—may develop what Dr. Meglathery describes as a "brain wired for danger." In other words, their nervous system becomes naturally biased toward detecting potential threats, often from an early age and sometimes with very little trauma required to establish this pattern. One proposed explanation is that altered hormone production results in relatively higher androgen exposure during development, influencing the amygdala—the brain region responsible for fear processing and emotional responses. Interestingly, research has also shown that individuals with hypermobility, who frequently carry TNXB variants, often have a larger-than-average amygdala. Cortisol Deficiency and Chronic Inflammation The second consequence relates to cortisol production itself. When the body cannot produce sufficient cortisol to meet the demands of ongoing stress, the brain compensates by releasing corticotropin-releasing hormone (CRH). CRH signals the adrenal glands to increase cortisol production. However, it also activates mast cells, triggering immune activation and promoting inflammation. This inflammatory cascade may contribute to a wide range of secondary conditions, including:
Rather than viewing these conditions independently, RCCX Theory proposes they may all stem from a shared disturbance in stress regulation. 3. C4. The third major gene within the RCCX module is C4, which plays an important role in immune regulation and autoimmune processes. Certain C4 variants have also been associated with schizophrenia. Although C4 mutations appear less frequently than TNXB or CYP21A2 variants, I regularly see families in which autoimmune diseases affect multiple relatives, suggesting that immune dysregulation is an important part of the broader clinical picture for some individuals. The CAPS Psychological Profile Dr. Meglathery introduced the term CAPS--CYP21A2 Mutation Associated Neuropsychiatric Spectrum—to describe the psychological characteristics commonly observed in individuals with this genetic vulnerability. Importantly, these traits often exist long before any formal psychiatric diagnosis and should not automatically be viewed as pathological. Common characteristics include:
Dr. Meglathery has also observed—and this has been consistent with my own clinical experience—that individuals with these characteristics frequently form close friendships, partnerships, and marriages with others who share similar traits. They are often drawn together through shared emotional depth, intellectual curiosity, creativity, and heightened sensitivity. As a result, children may inherit genetic tendencies associated with CAPS from both parents. She also notes an interesting physical observation: women believed to carry CYP21A2 mutations often demonstrate a more typically male finger-length ratio, with the ring finger longer than the index finger. This may reflect increased androgen exposure during fetal development. What RCCX Theory Contributes Of the three frameworks discussed, RCCX Theory provides the broadest biological explanation for why high sensitivity, psychiatric vulnerability, and complex chronic illness so often occur together. Rather than focusing exclusively on psychology or nutrient status, it integrates multiple body systems—including the nervous system, immune system, endocrine system, and connective tissue—within one genetic model. The theory also suggests practical treatment approaches beyond traditional psychiatric care. These may include:
One important limitation is that comprehensive testing for CYP21A2 variants is not yet widely available in routine clinical practice. Consequently, this gene is rarely discussed within conversations about the Highly Sensitive Person model, despite what I believe may be its significant contribution. RCCX Theory remains an evolving clinical model rather than an established medical consensus. Nevertheless, it offers one of the most compelling explanations I've found for the constellation of psychiatric symptoms, physical illnesses, and personality traits that I regularly see in clinical practice. IV. WHERE THESE MODELS INTERSECT Where Might Pyrrole Disorder and RCCX Theory Overlap? The similarities between Pyrrole Disorder and RCCX Theory are difficult to ignore. Both describe individuals who commonly experience poor stress tolerance, sensory sensitivities, persistent anxiety, chronic inner tension, connective tissue concerns, frequent infections, and autoimmune tendencies. Many of these overlapping symptoms can be explained, at least in part, by relatively low zinc levels. Zinc deficiency affects neurotransmitter function, immune regulation, connective tissue health, and the body's ability to respond to stress. However, there may be an even deeper biochemical connection between these two frameworks. The enzyme 21-hydroxylase, encoded by the CYP21A2 gene, contains a heme structure, which shares characteristics with pyrrole compounds. This raises an intriguing question: could abnormalities in 21-hydroxylase metabolism contribute to the accumulation of heme-related compounds and, ultimately, to Pyrrole Disorder? At present, this remains a hypothesis rather than a proven mechanism. However, during a discussion I had with Dr. Meglathery, she shared that she also believes there is likely a meaningful association. While additional research is needed, the biochemical rationale is compelling. This possibility matters because Pyrrole Disorder represents one area where we already have practical treatment options. Targeted nutritional therapy can complement what RCCX Theory highlights—that improving the body's stress response is a critical part of treatment. One theme consistently runs through all three models: stress. Whether the source is emotional, physiological, environmental, infectious, or toxic, stress serves as the common amplifier. Stress intensifies the experience of the Highly Sensitive Person, increases the challenges associated with CYP21A2 dysfunction through hormonal and inflammatory pathways, and has also been shown to increase pyrrole production. Although each framework approaches high sensitivity from a different perspective, they all point toward the same conclusion: improving resilience to stress is fundamental to improving both mental and physical health. BRINGING IT ALL TOGETHER For individuals who are highly sensitive and also living with psychiatric symptoms, neurological concerns, or chronic physical illnesses, both Pyrrole Disorder and RCCX Theory offer valuable perspectives because they move beyond simply asking "Why?" and begin answering "What can we do about it?" Taken together, these three frameworks complement one another remarkably well. The Highly Sensitive Person (HSP) model provides understanding, validation, and language. Rather than viewing sensitivity as a flaw, it reframes it as a naturally occurring trait with important evolutionary advantages and many unique strengths. The Pyrrole Disorder model introduces a specific biochemical explanation that can often be addressed through targeted nutritional treatment. It helps explain why stress affects some individuals so profoundly by demonstrating how nutrient depletion influences neurotransmitter function. Treatment doesn't remove a person's natural sensitivity—it helps reduce the anxiety, overwhelm, and emotional burden that may have accumulated over time. The RCCX Theory offers the broadest systems-based perspective. It connects nervous system regulation, immune function, hormonal balance, connective tissue health, and psychiatric vulnerability into a single biological framework. It also expands the range of potential treatment strategies, including nervous system regulation, mast cell support, hormonal optimization, and addressing the downstream effects of chronic stress and inflammation. Each model contributes something unique. Together, they offer a more complete understanding of why some people experience the world so intensely—and why that same sensitivity can sometimes become a source of emotional and physical suffering. Perhaps most importantly, these frameworks remind us that high sensitivity itself is not the problem. The goal is not to eliminate sensitivity, but to understand the biological and psychological factors that can make it more difficult to live with—and to address those factors whenever possible. If you recognize yourself in these descriptions—whether it's the heightened sensitivity, lifelong inner tension, low stress tolerance, or the feeling of constantly living on the edge of overwhelm—please know that there are meaningful avenues to explore. Understanding the underlying contributors can provide not only answers, but also practical tools that may significantly improve quality of life. If you're interested in working with a practitioner trained by the Walsh Research Institute to assess and treat Pyrrole Disorder and other nutrient imbalances that affect brain health—or if you'd like to learn more about Dr. Elaine Aron's work on the Highly Sensitive Person (HSP) or Dr. Sharon Meglathery's RCCX Theory—I've included those resources in the links below. 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 Other Sources: 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. Full text via PubMed 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. Full text via Wiley As always, I welcome your thoughts and questions. Until next time, Courtney
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Courtney Snyder, MDFor anyone experiencing brain symptoms. This blog (and weekly newsletter) is your guide to demystifying root causes and learning about surprising paths to healing. From a holistic - functional adult and child psychiatrist dedicated to helping people heal and thrive. Categories
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