An Endogenous Psychotogen in Schizophrenia?

Dr. Friedhoff proposed an endogenous "hallucinogen" as causing schizophrenia. This was DMPEA. This theory was disputed by Shulgin, who claimed that DMPEA was not a hallucinogen. However, Japanese work has shown that it is toxic to neurons. Thus it could be a toxin but not a hallucinogen. Mercury is such a substance. Mercury is very toxic to the brain, but it is not considered a hallucinogen. Mercury can cause mental disturbances by virtue of the fact that it is toxic to brain metabolism.

Zhou et al (1988)

This Chinese group reported the "contents of endogenous phencyclidine-like substances in cerebrospinal fluid of schizophrenic patients". This appears to strongly support Friedhoff except that the Chinese group reported "substances", meaning that more than one chemical was involved. Friedhoff only implicated DMPEA. DMPEA does have a chemical structure that bears some resemblance to phencyclidine.

The theory of the late Dr. Friedhoff of New York, also supported by Elnora van Winkle, who recently died, is a good one. Whether DMPEA is the correct substance is controversial. It might not be the only substance. Dr. Shulgin rejects the DMPEA theory even though the chemical structure of the substance is very similar to that of mescaline. A very slight change in chemical structure can produce a great change in potency.

Electron Microscopy of Schizophrenia

In 1969 Sukhorukova reported an electron microscopy study of biopsy material from the cerebral cortex of patients with schizophrenia and with epilepsy. In schizophrenia a wide variety of findings were reported.

FIndings

"Increased quantities of mitochondria were often present." In these organelles "swelling and central lysis of cristae were noted." The cytoplasm of most neurons contained lysosomoid structures similar to lipofuscin granules. "Signs of activation were seen in the glial elements." In astroglial cells "a considerable quantity of dark glycogen-like osmiophilic granules of varying sizes was found". If this was indeed glycogen, this would appear to suggest a partial failure of glucose metabolism in the brain. Since the brain depends very heavily on glucose for energy, this would be disastrous to thinking. There were "vauoloid inclusions". "Ribosomal structures were enlarged in the cytoplasm." The cisternae of the endoplasmic reticulum were dilated.

Since these cisternae are filled with amino acids, this appears to suggest a grave error in amino acid metabolism, perhaps a flooding of the cell with amino acids. A flooding of the cell with amino acids would explain the glycogen granules because the brain would burn some of the amino acids just to get rid of them. If the brain burned amino acids instead of glucose, this would be a kind of diabetes of the brain. The endoplasmic reticulum of the endothelium was activated. There was "intracellular edema". Sukhorukova concluded "these alterations were possibly associated with changes in protein metabolism".

Epilepsy

Some similar findings were reported in epilepsy including granules resembling lipofuscin. Sukhorukova noted that the destruction of membranal and granular structures "is especially prominent around lipofuscin granules".

There was a simultaneous disruption of the synthesizing and energy apparatus of the cell.

Interpretation

It appears that there is a severe metabolic error causing schizophrenia. The lipofuscin could be the residue of a toxin. Lipofuscin itself is not thought to be toxic, but this could be an abnormal type of lipofuscin or neuromelanin. It might look like lipofuscin, but it might be something else. But what do we do about it? That is the difficult part. It seems like a diet very low in protein should be tried.

A Possible Diet for Schizophrenia

There is massive evidence that schizophrenia is organic. Vogt & Vogt reported positive neuropathology findings. Vogt & Vogt reported alveolar degeneration. Metachromatic inclusions were Sudan Black B positive, indicating fat. Lipofuscin granules were seen in the cytoplasm. The Nissl bodies disappear. This work was confirmed by Baumer.

Freeman

Walter Freeman found abnormal lipid deposition throughout the diencephalon. In a review of this work, David suggested "a metabolic dysfunction of the neurons of the diencephalon." Vogt & Vogt Balloon cells were seen by the Vogts. This appears to suggest that the brain cells are over-eating some macronutrients.

Sacks (1959)

In 1959 William Sacks studied "the cerebral metabolism of isotopic glucose". The cerebral oxidation of glucose was low in "mental patients".

PKU

PKU is a form of inherited mental disease that is treated by diet. It seems that the amino acid phenylalanine is too high in the blood. The diet consists of fruits, vegetables, bread, pasta, cereals, and a special medical formula. Certain foods are banned. These foods are too high in protein. They include milk, refried beans, steak, pork chops, eggs, cheese, peanut butter, hamburger, nuts, and chicken.

Schizophrenia

Sokoloff & Kety found the cerebral oxidation was normal in schizophrenics, but all they measured was oxygen consumption. The total oxygen consumption of the brain was normal. However, Sacks found that the cerebral oxidation of glucose was low in "mental patients". Less brain CO2 was derived from glucose in psychotic subjects. This means that the brain is burning something else other than glucose in mental patients. This could be amino acids or fat. Sacks suggested "a greater dilution of some carbohydrate intermediates by protein ..." Sacks found that pyruvate was the the main site of the dilution. This is where amino acids dilute. Fat would dilute at acetate. Amino acids can convert into pyruvate.

Romasenko

Romasenko of Russia studied rats. They were injected with serum from schizophrenics. Deterioration of the membranes of cells and the membranes of the mitochondria were seen in the cerebral cortex.
Conclusions

There is massive evidence that amino acids are flooding the brain cells in schizophrenia. In 1974 the Russian workers Mishchenko & Bonartsev published a brilliant paper. They demonstated a toxic factor in the blood serum of schizophrenics. They used a lymphocyte assay. They found that the blood serum of schizophrenics caused a fourfold increase in lactate in the assay. Large lymphocytes with increased cytoplasm were found in the assay when incubated with the serum from schizophrenics. Large vacuoles appeared. Granules were seen. Breaks appeared in the outer cytoplasmic membrane. The vacuoles were transperant to the electron microscope, suggesting that they contained fat. This would be explained if amino acids were flooding the cells. The excessive amino acids could be converted to fat. Neuropathologists have reported fat deposits and tigrolysis in neurons. This is consistent with the amino acid flooding theory. The Nissl bodies, which are being destroyed, house amino acids. All of this data suggest a diet very low in amino acids.

The finding of an unknown toxic factor supports the theory of Friedhoff & van Winkle (1962) of DMPEA causing schizophrenia. The unknown toxic factor could be DMPEA.

Bibliography

1. www.associatedcontent.com/article/709479/moneydriven_medicine_vs_orthomolecular.html

2. www.associatedcontent.com/article/705601/the_alleviation_of_schizophrenia.html
3. www.associatedcontent.com/article/703807/why_orthomolecular_psychiatry.html
4. www.associatedcontent.com/article/696389/theories_of_orthomolecular_psychiatry.html
5. www.associatedcontent.com/article/693151/schizophrenia_is_organic.html