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RCCX Pathophysiology

RCCX Pathophysiology

How Your Genetic Blueprint Can Design a Personality Prone to Chronic and Psychiatric Illness

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Adrian Davidson
May 27, 2025
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In my first post on RCCX Theory, I detailed what the theory is, the genes involved, the related personality type, and how it is the genetic basis for intergenerational trauma and predisposes 20% of the population to having a highly sensitive immune system that is more likely to result in chronic physical and psychiatric illness.

The intent of this article is to dive deeper into the pathophysiology - the process by which acute and chronic stress lead to a differential hormonal milieu that results in a litany of symptoms and syndromes. RCCX Theory and its pathophysiology was originally identified by Dr. Sharon Meglathery, an internal medicine physician and psychiatrist with extensive experience with this population and the associated conditions. The flow charts in this article are based on and are an attempt to further break down and explain Dr. Meglathery’s pathophysiology diagrams.

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RCCX Pathophysiology Overview

At the root of RCCX genes is a distinct hormonal environment beginning at conception, driven by cortisol imbalance and disrupted production of multiple other hormones.

Cortisol is a steroid hormone that plays a vital role in survival, regulating homeostasis and how the body responds to stress. Cortisol regulates energy, metabolism, the immune system and inflammation, mood and fight/flight/freeze/fawn responses, cognition, and circadian rhythm (sleep-wake cycles).

There are two pathways through which the body produces cortisol:

  1. Basal Cortisol Production - This is the natural, circadian cortisol production, which is highest in the morning to help you wake up and have energy for the day, and is lowest at night allowing for rest and repair.

  2. Stress Induced Cortisol Production - This is a reactive production of cortisol in response to acute or chronic physical, emotional, or psychological stress.

People with RCCX gene mutations have a naturally lower basal cortisol production, which puts excess strain on both pathways of cortisol production. Depending on one’s environment and circumstances, one is either utilizing excess cholesterol and progesterone to make enough basal cortisol to maintain energy production and homeostasis, or one is relying on stress induced cortisol production to get them through the day.

The flow chart below details how the genes dictate the stress response that impacts the hormone production and ultimately spins out into chronic physical and psychiatric illness.

RCCX Pathophysiology Overview Flow Chart

Below, I will break down each piece of this flow chart and further describe how chronic stress can cause 21-hydroxylase overwhelm, which spirals further into various physical and psychiatric symptoms and syndromes.

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