Biochemistry and Schizophrenia

There is a great deal of data on schizophrenia. Much of this data is from neuropathology studies, and much of it is from biochemical studies. This article will be an attempt to combine the data from the two main approaches to reach a synthesis.

Neuropathology

I will start with neuropathology because this approach is older than the biochemical one. In 1897 Alzheimer studied "dementia praecox". He found a local disappearance of ganglion cells in the outer layer of the cerebral cortex as well as other findings. In a 20th century report he confirmed his earlier work. In 1930 Josephy described cell sclerosis and fatty degeneration in the cortical layers. In 1952 Winkelman reported a diffuse loss of nerve cells. Buscaino (1921) reported grapelike formations in the brains of schizophrenics. In 1906 Klippel and Lhermitte described areas of focal demyelination. In 1940 Bruetsch found rheumatic foci in the brains of schizophrenics. Papez (1948) reported inclusion bodies. Roizin (1952) studied biopsy specimens and found alterations in the medium-sized and large-sized pyramidal neurons. He found destruction of the tigroid substance, a finding also reported by Vogt & Vogt (1954).

Vogt & Vogt (1954)

C. and O. Vogt, a wife & husband research team, found anatomical alterations in all cases of schizophrenia that they studied. They reported "schwundzellen", which were abnormal cells. They reoported tigrolysis, cells filled with fat, balloon cells, etc. The nucleus becomes pale and disappears (karyolysis).

Metabolic Treatment

Linus Pauling favored a biochemical approach because he felt that the treatment would be biochemical. He felt that by experimenting with natural body and brain substances a cure could be found because the chemical environment for the mind was abnormal. A large number of studies have supported this point of view, although it was rejected by the APA (American Psychiatric Association). Detroit work by Frohman, Gottlieb, and others has implicated amino acids. It seems that amino acids are flooding the brain cells, particularly tryptophan. If this work is correct, and it was confirmed in the Soviet Union, it would explain many of the observations of the Vogts. Synthesis A flooding of the cells with amino acids would explain tigrolysis, balloon cells, cells filled with fat, and cell death. It would also explain the nuceus becoming pale because RNA is in the nucleus. RNA is dark. It is shipped from the nuceus to the tigroid substance where it is used to make proteins out of amino acids. A flooding of the tigroid substance with amino acids would cause increased demand on RNA. It could also destroy the tigroid substance.

It would seem that a logical metabolic treament would be a special diet very low in amino acids. It might also be useful to restrict fat because the cells fill with fat.

A Brief History of Psychiatry

This history will not deal with Freud and his followers because I believe that Freud's theories were largely false. No doubt there is a subconcious mind, but Freud did not use scientific methods. New ideas are not always greeted with enthusiasm. For example, in 1600 Bruno was burned at the stake for his ideas on astronomy. In the case of Freud, the skeptics, including Kraepelin, were right.
There is an overlap between psychiatry and neurology. For example, Gilles de la Tourette was a 19th century French neurologist. The syndrome named after him is both psychiatric and neurological. It has both psychiatric symptoms and neurological symptoms (tics). Other great 19th century French scientists were Esquirol, Charcot, and Janet. Charcot was interested in both neurology and psychiatry.

Giants of Science: Southard

Elmer Southard was director of the Psychopathic Hospital, later to be called "Mass. Mental". He was also a professor of neuropathology at Harvard Medical School. Southard favored "microlocalization", meaning that brain parts are not mutually exchangeable in function like liver parts. He felt that Wundt was against localization. In 1906 E. E. Southard began to study "the brain problems of dementia praecox". He published his first paper on this in 1910.

Dementia Praecox

In 1910 Southard reported "anomalies or scleroses in particular brain-regions". He found 23 out of 25 brains to be "significantly anomalous". He felt that "disease of a toxic or metabolic nature" caused anomalies in "weak places". This might be true, but it may also be that the toxin is created in certain regions of the brain. He reported "parenchymatous (neuronic)" and "interstitial (neuroglia)" changes "in the brains of certain psychopathic subjects, especially in dementia praecox". In other words he found nerve cell losses and gliosis, including satellitosis. It is now know that gliosis signifies the presence of a toxic factor. Gliosis is incompatible with a neurodevelopmental disease. At this time Bleuler had invented the term "schizophrenia". However, it was not yet popular.

Gosline

Dr. H. I. Gosline (1917) found lesions demonstrable by fat stains. Southard tried this but he obtained "too rich a display of lesions, as a rule, to permit correlation". In other words, Southard tried to relate particular types of mental disease to particular sections of the brain. Alzheimer and Cotton (1915) reported fat-stained cells and deposits.

Southard felt that delusions were based on frontal lobe disease. It is now known that the frontal lobes contain dopamine, although dopamine had not yet been discovered at the time of Southard. Later work has confirmed the gliosis and nerve cell losses reported by Southard. The Vogts (1952) confirmed the neuron losses. At the time of Southard the term "neuron" was not yet popular. Stevens and other workers have confirmed the gliosis. Southard published a number of brilliant papers between 1910 and 1920. Unfortunately he died shortly after that. He was a contemporary of Alzheimer. Alzheimer published brilliant papers from 1897 to 1913. The fat deposits would appear to suggest that the brain cells are overeating some macronutrients. This would probably not be glucose since the person would pass out if their brain was taking in too much glucose. This is seen in diabetes. Therefore it would have to be either fats or amino acids or both.

German Science

In the 19th century there were many brilliant German scientists. Wernicke, Griesinger, Wundt, Kahlbaum, Hecker, and Kraepelin were prominent. Austria produced Meynert and Freud. Franz Kallman was a brilliant German scientist of the 20th century. Kallman demonstrated that schizophrenia is genetic. Similar results were reported by Eliot Slater in England. In 1907 Alois Alzheimer published a report on the disease that is now named after him. Previously it was called "dementia", a term that is still used. Alzheimer reported plaques and tangles in the brain. These findings were confirmed by later workers.

American Work

In the 19th century the American work lagged behind the German work. However, the US produced Huntington, who now has a disease named after him. The disease is neurological, but it can present psychiatric symptoms, including euphoria.

Early psychiatric contributed mostly to the classification of diseases. This was sometimes controversial because many psychiatric diseases have physical bases that are not yet understood. Thus some diseases were considered "organic" and some were considered "functional". In reality they are all organic, but in the "functional" ones the organic basis has not yet been discovered. For example, the Tourette syndrome, named after a brilliant French scientist, is known to be organic because there are tics.

Down syndrome is a form of mental retardation which is known to be organic. Anorexia no doubt has an organic basis, but this organic basis is no yet known. In Pick's disease there is obvious neuropathology.

Cushing was another brilliant American scientist. Cushing's disease is a physical (endocrinological) disease which has psychiatric symptoms as well as physical symptoms.

Psychotomimetic Drugs

Certain drugs, including LSD, can mimic a psychosis. Marijuana is another example. Osmond, Smythies, Harley-Mason, Stockings, Hoffer, and others have suggested that an internal substance in the body poisons the brain, producing psychosis. Amazingly, LSD was once used as therapy! This is by no means the only theory. D. W. Woolley thought that a deficiency of serotonin was involved. However, postmortem brain measurements of serotonin were normal, destroying his theory.

Toxic Factors

Macht used plant growth as an assay. He reported that serum from schizophrenics retarded plant growth. Rieder did similar experiments with spiders. Serum from schizophrenics was given to spiders, causing them to spin bizarre webs. Bishop used learning in rats as an assay. Reward learning was severely retarded by the administration of serum from schizophrenics.

Positive Findings

In 1957 McGeer et al reported that schizophrenics excreted a higher than normal concentration of aromatic compounds in the urine. Similar work was reported by Buscaino of Italy. Friedhoff & van Winkle (1967) reported DMPEA in the urine of schizophrenics. Bourdillon et al in England reported similar findings. They found a "pink spot" on their chromatograms matching the pink spot reported by Friedhoff & van Winkle. Since DMPEA is an aromatic compound, this is consistent with the work of the Canadian group McGeer et al. The above work supports an earlier hypothesis of Osmond & Smythies. This hypothesis suggested pathological transmethylation.

Heath

Heath reported a toxic blood protein, which he called "taraxein". He localized schizophrenia to the septal area of the brain using surgically implanted electrodes. Heath's localization to the septal area was confirmed by the Canadian neuropathologist Averback in 1981. His toxic factor was confirmed by Bergen and also by a Detroit group (Frohman et al). The Detroit group called it "factor 1" because they thought that more than one toxic factor could exist.

Detroit Work

The Detroit group found that their factor had a high lipid content. It was a protein, however. The Worcester Foundation group (Bergen et al) found that their protein was a carrier of a small active molecule. Heath's Tulane group also demonstrated this. It was an alpha globulin. It was labile (unstable) in solution. A Russian group from Moscow reported similar findings in 1967. The Detroit group found excess lactate in their assay. They found that the excess lactate was caused by amino acids flooding the cells, particularly tryptophan. Krasnova of Russia confirmed the excess lactate. Bergen confirmed the fact that the factor was toxic using a climbing time measure for rats.

Conclusions

Freud and his disciples built castles in the air. They did not use scientific methods. Much closer to the truth was V. M. Buscaino, who reported pathologic amines in the blood and urine of schizophrenics. He concluded that schizophrenia is an "amino-toxicosis". Buscaino published brilliant reports in 1952 and 1970. He thought that the liver was involved. He presented a report at the First International Congress of Neuropathology in Italy.

He found evidence of functional insufficiency of the liver. There was detoxification power impairment. Other workers found abnormal blood proteins. Beckett and Gottlieb (1970) and Frohman & Gottlieb (1974) reported these findings. Lozovsky of Russia reported similar findings.

After writing many books on psychoanalysis, Freud committed suicide in 1939. His theories, based on naval contemplation, were false. He failed to use scientific methods.

It may be that DMPEA is the small molecule carried by the blood protein. The DMPEA appears to cause the cells to flood with amino acids. It would appear that a diet low in amino acids should be tried as a treament, although the Detroit group never suggested that. It is my own idea.

Bibliography

1. www.associatedcontent.com/article/723727/an_endogenous_inhibitor_of_monoamine.html

2. www.associatedcontent.com/article/722243/schizophrenia_an_error_in_homeostasis.html

3. www.associatedcontent.com/article/721845/phytochemicals_for_schizophrenia_cancer.html

4. www.associatedcontent.com/article/717973/progressive_brain_tissue_loss_in_schizophrenia.html
5. www.associatedcontent.com/article/718067/an_endogenous_psychotogen_in_schizophrenia.html