In 1920 Gurd reported many abnormalities in schizophrenia. These included "loss of chromatin in nerve cells, granular degeneration of body and dendrites, very marked alterations in the nucleus with folding and irregularity of nuclear membrane and metachromatic alteration of nucleoli, severe fatty degeneration of glia and nerve cells" etc.
ALZHEIMER
Although professor Alzheimer is most famous for the disease named after him, he spent years studying "dementia praecox". He reported lipoid degeneration of the nerve cells. This substance, or substances, heaped up in the cells. Alzheimer invented the Alzheimer-Mann stain. Alzheimer's work was confirmed by Gurd, who reported "the axis cylinder is swollen, altered in color, and torturous". "The myelin is frequently seen clumped into balls." It is now known that the myelin sheath is an important part of the neuron cell membrane.

NEUROPATHOLOGY
Gurd reported (1920) "irregular vacuoles are constantly seen, sometimes forming an irregular beading around the border of the cell". Vacuoles often represent food for the cell. "These vacuoles are also seen at the root of the axis cylinder and here and there on its course away from the cell body." No doubt this lipoid material may reflect a transport error of the cell in which the cell is gorging itself with some kind of food. Gurd also reported "the number of glia cells is greatly increased especially in the third and sixth layers." This represents gliosis, which is often seen due to a toxic factor.
Ultimately the problem must be solved on a biochemical basis. The biochemical errors involved must first be understood and then corrected, if possible. This author thinks that it is possible, but difficult due to the complexity of the disease. Schizophrenia may even be a cluster of different diseases, all diseases of the brain.

Clipart showing the gross anatomy of the human brain is presented on the page entitled "Gross Anatomy".
WUNDT
Wilhelm Wundt was a brilliant German scientist who was born in 1832 and died in 1920. Wundt started the first psychology research laboratory. He was a prolific writer, authoring books and papers. One book on physiological psychology was published in 1902 and was translated into English in 1904. Wundt probably influenced Kraepelin, a brilliant German psychiatrist.

BIOCHEMISTRY
In 1952 a brilliant article was published written by Osmond & Smythies with remarks by Harley-Mason. This article suggested that an internal methylated substance similar to mescaline was causing schizophrenia. It was suggested that the substance was a catecholamine such as DMPEA. This theory was supported in 1962 by Friedhoff & van Winkle, who found DMPEA only in schizophrenics. This was then called the "pink spot hypothesis".
The reason it was called the "pink spot" is that DMPEA makes a "pink spot" on the chromatograms of urine of schizophrenics. Another theory is that more than one substance makes a pink spot. Thus the "pink spot" could have more than one ingredient. The pink spot contains DMPEA, but it could also contain similar substances. A number of experiments have shown DMPEA to be toxic to animals. Bergen did experiments on rats where the rats climbed ropes.

TOXIC FACTORS IN SCHIZOPHRENIA
Various groups have reported toxic factors in schizophrenia using different assays. Lideman of Russia used erythrocytes as an assay. It was found that the unknown toxic factor produced hemolysis in the assay. A similar assay was used by Frohman of Detroit, who also reported hemolysis as well as other findings. Beckett et al of Detroit (1963) found that energy production was abnormal in schizophrenia.
Leach et al, a Tulane group, reported "taraxein", a serologic fraction in schizophrenia, in 1963. Like the Russian group Lideman & Bokova (1967), they isolated their factor from blood serum. The Detroit group isolated theirs from plasma, which is similar to serum but not identical. Krasnova (1965) used serum to confirm the Detroit work on carbohydrate metabolism. Latham et al (1963) reported an effect on membrane permeability. Their factor was a protein.

ORLOVSKAYA
In 1983 Orlovskaya of Russia reported schizophrenia to be a toxic encephalopathy with metabolic changes in the brain. She reported lipoid sclerosis, synaptic degeneration, proliferative changes in the glia, edematous changes of neurons, etc. Pathology was seen in the cortex in layers III and V, especially in the frontal and temporal areas.
Orlovskaya published a brilliant article in 1983 in a book called "Handbook of Psychiatry". Unfortunately this book never appears to have been translated into English. The article was entitled "Pathological Anatomy of Psychoses". Previously D. D. Orlovskaya had written a journal article documenting studies demonstrating a toxic factor in the blood of schizophrenics. Rabbits were used in her assay. The blood sugar of the rabbits rose after they were injected, suggesting that the factor slowed glucose metabolism.

SOUTHARD
A number of brilliant American neuropathologists have reported positive findings in schizophrenia. In 1914 and 1915 Southard reported enlargement of the cerebral ventricles. E. E. Southard reported "cortex lesions and anomalies" in "dementia praecox", a term then used for what is now called "schizophrenia". His 1914 and 1915 articles were published in the American Journal of Insanity.
A brilliant current worker, Janice Stevens, feels that Southard was correct. Stevens (1997) feels that Southard's work was "widely replicated".

GLIOSIS
A large number of studies have reported gliosis, which suggests a toxic factor. Neurodevelopmental disorders do not show gliosis. In 1972 Nieto and Escobar reported gliosis using Hortega's stain. Gliosis was seen in the mesencephalic reticular formation, hypothalamus, thalamus, periaqueductal gray matter, and hippocampal formation.
In 1982 Janice Stevens confirmed the work of Nieto and Escobar. She found gliosis in the basal forebrain.

CONCLUSIONS
The popular but false neurodevelopmental theory has been repeatedly been proven false by findings of gliosis. A century of neuropathology data has been ignored by enthusiasts for the neurodevelopmental theory. This data goes back to Alzheimer in 1897. Rather the data favors an unknown toxic factor. The toxic factor causes deposits of lipids.
There are strong reasons to believe that the factor may be DMPEA, a metabolite of dopamine. The DMPEA appears to cause a flooding of the cell with amino acids, causing a backup in glucose metabolism. The backup in glucose metabolism causes glycogen droplets to be deposited. The treatment is probably a diet very low in amino acids and perhaps low in fat because the excessive amino acids are in part converted to fat.