Schizophrenia's Three Biotypes & Walsh Nutrient Therapies
& How the Prevailing Idea of Schizophrenia as One Condition is Limiting the Development & Recognition of Effective Treatments
“If things are not so good, you maybe want to imagine something better." John Forbes Nash, Jr.
You might know John Nash, Jr. as the brilliant mathematician portrayed by Russel Crow in the movie “A Beautiful Mind.” The movie, though not faithful to Nash’s actual story, does effectively show his spiral into psychosis and severe chronic mental illness.
Schizophrenia affects 1 in 300 people or 24 million people worldwide (2.6 million in the U.S.) It remains the most treatment resistant psychiatric condition.
In this newsletter, using Nash’s story as a reference point, I’ll discuss:
Theories attempting to explain schizophrenia.
How the belief that all people with schizophrenia have the same biochemical disorder has resulted in lack of effective treatment and problematic side effects for many.
Research from the Walsh Research Institute which has identified three distinct biotypes for schizophrenia (undermethylation, overmethylation and pyrroluria), each with different predominant symptoms and biochemical needs.
How those of us trained by the Walsh Research Institute assess and treat schizophrenia.
The real story of John Nash’s life not shared in the movie.
Most with schizophrenia are not brilliant mathematicians who become Nobel Laureates. Many are homeless. I use Nash’s story, because it is known by many and because he appears to have the most common form of schizophrenia - undermethylated (along with 70% of those with this illness).
Here are my 10 thoughts on Schizophrenia
1. Diagnostic Criteria
(Shortened from the D.S.M. V) Must have 2 of the following with one of those being of the first three:
Delusions (believing something despite evidence to the contrary - belief not based in reality)
Hallucinations (hearing, seeing or feeling things that are not there)
Disorganized speech (reflective of disorganized thoughts)
Disorganized or catatonic behavior (inability to move normally)
Negative symptoms - blunted emotional expression, decrease in quantity of words spoken, decreased motivation and decrease in ability to experience pleasure.
2. Course of Illness
Whether someone has more delusions or more hallucinations or a mix, the course of illness typically involves relative normalcy prior to the onset of psychotic symptoms, cognitive deficits and loss of social skills. Nash’s onset of illness at the age of 30 was relatively late. The average onset for men is late teens to early 20’s and for women late 20’s and early 30’s. Men tend to have more severe symptoms. This sex difference has been attributed to the protective effects of estrogen.
3. Current Theories
All are based on the premise that the 24 million with schizophrenia worldwide have the same biochemical condition.
Genetic hypothesis: It is well understood that schizophrenia often runs in families, but not in a way that can be predicted.
Dopamine Hypothesis (has been the prevailing theory) came out of the 1950’s discovery of chlorpromazine (Thorazine), a medication that blocks some dopamine receptors in the brain. While many with schizophrenia benefitted, especially with decrease in symptoms like hallucinations and delusions, negative symptoms and cognitive symptoms did not similarly improve, and some developed persistent movement disorders. These same challenges persist even with newer antipsychotic medications. Relative to its predecessors, Clozapine has little impact on dopamine activity. But for its own dangerous potential side effects, including low white cell count, it would probably be used more for treatment resistant schizophrenia.
Glutamate hypothesis: Basically there is low activity at the N-methyl D-aspartate (NMDA) receptor. (More on NMDA in the future).
Neurodevelopmental disorder. Part of our maturation involves the normal elimination of certain neuronal connections during adolescence. This theory suggests that in schizophrenia, this process occurs excessively. Fitting with this theory is a higher rate of mutation on the C4 gene resulting in too much C4 - a protein important in “synaptic pruning” (like an overzealous gardener with pruning shears). C4 is one of the genes in the RCCX gene complex.
Inflammation: Inflammation is increasingly accepted as part of this and other brain conditions. Studies have shown higher levels of proinflammatory and anti-inflammatory cytokines in the blood of those with both first episodes and recurrences.
4. Current State of Treatment of Schizophrenia
From the Lancet Journal (one of the leading medical journals) editorial last month introducing the initiative to bring more attention to treatment of those with severe mental illness in 2024:
“ Although tolerability has improved with newer antipsychotics, they are associated with extensive side-effects, especially extrapyramidal side-effects from blocking dopamine. Long-term metabolic effects, such as an increased risk of cardiovascular disease, are also possible, and regular drug monitoring is often required. Such factors contribute towards underprescribing of antipsychotics by clinicians and poor adherence by patients…”
In stark contrast, Dr. William Walsh continues to train doctors around the world, who think very differently about schizophrenia and treatment.
5. Walsh Theory of Schizophrenia
Over a span of 40 years, the Walsh Research Institute looked at nutrient levels in over 30,000 people. Out of this data came a great deal of information about biochemical factors in those with brain symptoms. From this emerged three major biotypes of schizophrenia. This is a big deal, because if you are putting three biochemically different groups of people together and trying to treat them all with the same types of medication, you will get what we’ve seen over the last 70 years. To oversimplify Dr. Walsh’s theory - most with schizophrenia come into the world with 1) a vulnerability to epigenetic errors that can alter genetic expression and 2) a vulnerability to high oxidative stress (when our inherent protective antioxidant system is overwhelmed by something like toxicity, trauma, inflammation or other factors). These two vulnerabilities, in combination with severe emotional or physiological stress, leads to overwhelming oxidative stress causing an alteration in gene expression and the onset of illness. These vulnerabilities, for most who develop schizophrenia, appear to be due to methylation imbalances.
6. Three Walsh Biotypes of Schizophrenia
Overmethylated Type - “a sensory disorder” marked by auditory, tactile or visual hallucinations. High physical activity, high anxiety, and paranoia are also common.
The biochemical imbalance involves a folate deficiency with high methyl resulting in high dopamine activity (fitting with the dopamine hypothesis) and high norepinephrine (adrenaline) activity. This was once the most common type of schizophrenia at 42% (from 1960-1980) and now the least common at 8%. (Discoverd 2018). That’s a big problem since medications were largely designed around this group that is now relatively small. There is also decreased activity at the NMDA receptor (fitting with glutamate hypothesis)
Undermethylated Type - “a thought disorder” - I highly suspect John Nash was undermethylated. Prominent symptoms include delusions and in some cases catatonia. OCD symptoms and social isolation may also be present.
The biochemical imbalance involves low methyl, high folate resulting in low dopamine activity (NOT fitting with the dopamine hypothesis and current psychiatric medication targets, which further lower dopamine activity), low serotonin activity and increased activity at the NMDA receptor. This doesn’t mean that antipsychotics don’t provide some benefit from other mechanisms including antihistaminic effects which could cause calming, but also sedation.
Undermethylated is now the most common type of schizophrenia at 70% (it was 28%). In 2018, Dr. Walsh identified this big shift in the methylation biotypes. (Undermethylation appears to be increasing in our society over the last 30 years).
Just knowing that John Nash was a mathematician points to undermethylation (as those of us in detail oriented types of work are usually undermethylated). Delusions also seemed to be his most prominent symptom. Like many he also may have had elevated pyrroles as well.
Pyrrole Type - Prominent symptoms include auditory hallucinations, delusions, rapid mood swings, high anxiety.
The biochemical imbalance includes high pyrroles in urine and blood causing zinc and B6 depletion. Both of these nutrients impact neurotransmitters resulting in low GABA activity and further impacts at the NMDA receptor.
Currently 15% of those with schizophrenia have pyrroluria. This can also be occurring with under and overmethylation
7. Diagnosis of Walsh Biotypes
This includes assessing symptoms, traits and lab data. Because most psychiatric medications have antihistamine effects, the whole blood histamine test (which we typically use to assess methylation) can be very unreliable. Instead we will use a methylation profile (from Doctor’s Data). Pyrrole testing involves a simple urine test. Other important blood tests include plasma zinc, serum copper and ceruloplasmin. We interpreted results using optimal reference ranges based on the Walsh data (which differs from the typical lab ranges).
8. Walsh Nutrient Protocols
Based on lab data, the identified biotype and other factors such as age, weight and health conditions, a nutrient protocol (a combination of specific supplements targeting deficiencies and methylation) is put together. Such a protocol can be given with psychiatric medications. In my own practice, I would not start someone with severe symptoms on a protocol until they are relatively stabilized with the help of medication before seeing me for this type of treatment. Decreasing medication is generally not recommended until someone is on the protocol for at least 3-4 months. Many, if not most, are on more than one medication. Once they are starting to benefit from the protocol, their prescribing doctor is usually more confident about gradually starting to lower one medication at a time and in a stepwise fashion.
9. My Clinical Experience
Because of the severity of this illness, improvements can be life changing, making treating schizophrenia one of the most satisfying conditions to treat using the Walsh approach. Identifying and addressing the sources of high oxidative stress, however, are often necessarily in combination with the protocols. For example, I find mold toxicity to be common in those with brain symptoms, but especially those with severe mental illness including schizophrenia.
10. A Beautiful Mind
In real life, John Nash stopped taking his psychiatric medications. The story line in the movie has him achieving a degree of stability from meds. Apparently, this significant change was made out of concern that the true story might encourage others to stop their medication. I wouldn’t want to promote people going off their medication either. Nash stopped his meds because he felt they blunted his intellect. And like many with schizophrenia, he didn't like how they made him feel. The movie avoided the problematic reality of psychiatry - that when it comes to schizophrenia, there are very poor choices. After 25 years of illness marked by severe delusions and repeated hospitalizations, John Nash had a degree of recovery not typical of this illness. This was the around the age of 55. He died at 86 with his wife in a car accident and was survived by his 56 year old son, who also had schizophrenia (and who did take medication for his illness).
“If things are not so good, you maybe want to imagine something better.”
Though I don’t think John Nash was talking about the state of psychiatric treatment, I do believe Dr. Walsh’s approach (backed with extensive data) heeds that call and has imagined something better.
Until next time,
Courtney
Medical Disclaimer: This newsletter is for educational purposes and not intended or implied to be a substitute for professional medical advice, diagnosis or treatment for either yourself or others, including but not limited to patients that you are treating (if you are a practitioner). Consult your own physician for any medical and psychiatric issues that you may be having.