How Mutations On One Gene May Predispose Us to Most Psychiatric Conditions

RCCX Theory, CAPS Psychological Profile, Finger Length Ratio & The Potential Intersection of Pyrroles & RCCX Theory

“Woman Plans Mother Nature Laughs” Cut paper collage recreated with a gust of wind.

In the last newsletter, I introduced Dr. Sharron Meglathery’s RCCX theory, starting with hypermobility as a seeming red flag for this genetic vulnerability. Hypermobility doesn’t have to be present. I see evidence of RCCX mutations in many, if not most of the patients I see, and in their families.  

In this newsletter, I’ll provide a brief review before discussing common psychological traits and strengths.  I’ll also comment on the striking overlap between symptoms of RCCX mutations and pyrrole disorder.    

RCCX

RCCX is a module of four genes. Three of the genes appear to be extremely  important to our health.  Two of those genes have a high rate of mutation - one impacts our connective tissue (and thus hypermobility) and the other impacts our hormonal stress response. The third gene relates to our immune system (C4).  

CYP21A2 Encodes For 21-Hydroxylase

The most important gene in the module, when it comes to psychiatric disorders,  is CYP21A2, the gene involved in our stress response.  CYP21A2 codes for 21-hydroxylase, an enzyme needed to make cortisol from 17 hydroxyprogesterone.  If there is a mutation (of which there may be many and to varying degrees), we could be low in cortisol or we could be high in cortisol.  We could even start out high (when under stress) and then overwhelm this enzyme and be low. 

RCCX Theory

“RCCX Theory posits that CYP21A2 mutations predispose to most psychiatric conditions - bipolar disorder, anxiety disorders, compulsive behaviors, mood disorders, PTSD, dissociative disorders, eating disorders, aspects of autism (sensory sensitivities, hyper-focus, special interests, females with male brain wiring, excellent systems approach, processing superiority, social awkwardness) except schizophrenia which is linked to C4.  Schizoaffective disorder may be C4 mutations co-inherited with CYP21A2 mutations.”  - Sharon Meglathery, MD

Though I’m not focusing on it here, mutations can also lead to complex chronic illness (MCAS, POTS, CIRS, CFS, etc,) as discussed in the last newsletter.

How CYP21A2 Mutations Appear to Contribute to Brain Disorders (per RCCX Theory)

1. Inflammation from low baseline cortisol in combination with high stress. When we are under more stress (emotional or physical), our body needs more cortisol.  If 21-hydroxylase has a mutation and the demand for cortisol exceeds what can be  made, the brain puts out corticotropin releasing hormone (CRH). This tells the adrenal glands to make more cortisol. CRH binds to mast cells and turns on the immune system, which leads to brain inflammation.  

2. Brain wired for danger (by age 5). The failure of 21-hydroxylase to keep up can result not only in a low baseline cortisol, but also the build up of androgens and 17 progesterone.  The higher androgens appear to impact the developing brain, specifically the amygdala. Studies have found that those with hypermobility have a larger than normal amygdala, which is fitting with the RCCX theory.   The amygdala is the fear and emotional center of the brain.  It is suspected that this is also the case in many of those with a 21-hydroxylase mutation without hypermobility. 

CAPS Psychological Profile