What Causes Schizophrenia?

September 17, 2023

What Causes Schizophrenia?

Schizophrenia is an odd disease. It strikes teenagers (most often) who have otherwise been normal. They often present with a characteristic prodrome of disordered thinking. That prodrome is better treated with fish oil than any other pharmaceutical, reducing the odds of flipping into full fledged schizophrenia by some 50-70%. That is a very interesting clue (We will get back to this). Supposedly the cause is unknown, though many conjectures exist. Separated twins continue to have an increased risk so there is some acknowledgement that there is a genetic risk involved.

Schizophrenia’s symptoms are myriad. Disorder thinking, troubled relationships, hallucinations all can be part of the symptom mix. It’s a catastrophe for the person involved. They frequently end us unable to hold a job, finish school, engage in healthy relationships or all the other hallmarks of a fulfilling life. 

There is hope here. Follow this thread. We have known for almost 20 years that Schizophrenia shows disrupted white matter on MRI diffusion studies. That means the myelin in the brain has been degraded. Instead of nice, neat 10-15 layers of myelin, there is too much water and too little plasmalogen lipid in the myelin. Plasmalogens make up 70% of myelin. They are the antioxidant of FIRST RESORT designed to protect the precious brain cells from damaging chemicals. Hence, when reactive oxygen species show up and overwhelm the normal defenses, plasmalogens are damaged and need replacement. 

Microglia are the garbage trucks of the brain, tasked with cleaning up damaged cells so that the regular undamaged cells can get on with the work to be done. Evidence of microglial activation is also well established. “Upon activation, microglia release key proinflammatory cytokines and free radicals, which are well-recognized neurotoxic factors contributing to cognitive decline.” Microglia are sloppy. In the release of those inflammatory cytokines, they damage the region around the damaged axon, making a falling domino effect. They then have to clean up the next cell, and the next, and the next.

That domino effect occurs because the cells responsible for making myelin, called oligodendrocytes, have got themselves in a biological corner. The surface area of membrane they are responsible to maintain is massive. Each oligodendrocyte has multiple pseudopods extending out to make multiple layers of myelin around the axons. That myelin works best if there is very little water in it. That feature allows it to insulate the axon for electrical conductivity. A well-myelinated brain will conduct electricity at 100 meters a second. A newborn baby with virtually no myelin has a conduction speed in their brain of 1-2 meters a second. If you imagine a regular cell being a football (it is the season, after all). A regular cell has a membrane around the football. That’s not hard to maintain. If damage happens, it can send a repair team out to fix it. An oligodendrocyte has a membrane the size of a football field, compared to its football. Maintaining that is no small task. To send out repairs, when there is no water to work with, ties its hands behind its back. You might call that the Plasmalogen Bottleneck. The Oligodendrocyte can’t repair the damaged membranes without a lot of help, if at all because of those sloppy microglia that keep damaging the next cell over. 

Is there evidence of plasmalogen damage in schizophrenia. Yup, yup, yup. When peroxide or the dreaded OH- ion meet up with the vinyl ether bond on the surface of the myelin, the double bond is degraded and destroyed, making a byproduct called malondialdehyde. Guess what we find in schizophrenia? High malondialdehyde.

This speaks to the cause of schizophrenia. Some unrecognized mitochondrial failure initiates a cascade of reactive oxygen species. They overwhelm the normal defenses and reach the white matter ecosystem. Oxidative damage happens and axons no longer function properly. That’s where fish oil comes in. Gray matter plasmalogens are where DHA from fish oil ends up. If we give the poor, struggling brain cells just a modicum of help, they get better. They are just burning up from the oxidative stress and need a whole raft of support mechanisms to fix them.

That’s where plasmalogen supplementation comes in. It hasn’t been proven yet, but all the features are there. What has changed is the beginning ability to manufacture replacement plasmalogens. Mitochondiral support, methylation support are all easy to accomplish. Just flood the zone and give the poor brain a chance!

WWW.What will work for me. I’ve heard of one anecdote of a psychotic break with hallucinations given 200 mg/kg of plasmalogens a day resulting in a complete remission of symptoms in just 7 days. That is just mind boggling, to coin a phrase. What I’m wrapping my brain around is the concept of the Plasmalogen Bottleneck in the oligodendrocyte. That makes sense to me. We evolved such an amazing brain with so many fantastic capabilities, but in so doing, opened up a key vulnerability. That football field of membranes is a bear to maintain and just doesn’t do it very well when ongoing oxidative stress happens. Well, now we can fix it. Probably, hopefully. Turning off the oxidizing stress source may be key. More research to follow


Lipid Health Dis., Mayo Clinic, Neuropsychopharmacology, Nature, Noro Psikiyatr Ars, Nature,

Pop Quiz 

1. What is the MRI finding in the white matter of brains with folks suffering from schizophrenia?             Answer: White matter diffusion defects. 

2. How can you prove that there is widespread microglial activation in the brains of schizophrenia sufferers?       Answer: High malondialdehyde 

3. Why do presenting schizophrenics often improve with extra fish oil?                             Answer: Fish oil, DHA, its integral to making plasmalogens. That's where fish oil is used in the human body. The brain is begging for building blocks so it can function properly. 

4. What is the Plasmalogen Bottleneck?                            Answer: My label for an observed phenomenon. Oligodendrocytes, the cells that make myelin has a responsibility to maintain many times their own natural surface area of membrane that is wrapped around axons to insulate them and allow them to conduct electricity rapidly. That wrapping is hard to access because, of a necessity, all the water is squeezed out. When myelin is damaged, the cell responsible to repair it just can't.

5. Will schizophrenics improve with plasmalogen therapy?                      Answer: It is a tantalizing hypothesis that addresses all the physiology properly with no toxicity. Nothing else has worked to date. We are just waiting for proof.