The Molecular and Cellular Pathology of Schizophrenia

In 1987 Smeraldi et al reported "increased concentrations of various amino acids in schizophrenic patients". This was blamed on "heterozygosity". In other words, genetic errors cause schizophrenia.
Smeraldi et al (1987)

These Italian workers found "AAD" (amino acid disorders) in "schizophrenic patients". It seems that amino acid disorders cause cerebral dysfunction.

Freeman et al (1972)

These workers studied homocystinuria, which presented as schizophrenia. This disease has a defect in methylation. Conclusions are difficult. Further research is needed. If amino acid metabolism is abnormal in schizophrenia, a diet could be used as a treatment. This diet would be very low in amino acids.

Amino acids are very important in the brain. For example, certain amino acids are neurotransmitters, including aspartic acid, glutamic acid, glycine, homocysteine, taurine, etc. Classical neurotransmitters such as dopamine are inactivated by catabolic enzymes. But why is this important to psychiatry? It seems that the brain is made up from the food you eat, which includes amino acids!

Norepinephrine

Norepinephrine, which comes from amino acids, is found in the locus coeruleus. The locus coeruleus is found in the brain stem.

Serotonin

Serotonin has cell bodies in the raphe nuclei. The raphe nuclei are located near the base of the brain. Projections reach the cerebellum and other parts of the brain.

Dopamine

Many cell bodies are found in the substantia nigra, and some are also in the ventral tegmental area and in the arcuate nucleus. These areas are in the basal forebrain. There are also other neurotransmitters, including acetylcholine and GABA. However, this article will be too short to discuss them all.

Panic Disorder

Panic attacks have been induced in lactate infusion studies. The fact that lactate can induce panic suggests a possible excess of lactate in panic disorder. This work strongly supports Detroit research in which lactate was reported to be high in schizophrenia. Psychotherapy has been used as a treatment in panic disorder and in phobias.

Schizophrenia

PET studies have been done in schizophrenia. These studies have revealed regional neuronal metabolic changes. Glucose metabolism was studied. Hypometabolism in the frontal cortex was reported in various studies.

Drugs

Certain drugs can cause delirium. The American Psychiatric Press Textbook of Neuropsychiatry presents a very long list of such drugs. Corticosteroids, Carbidopa, Levodopa, etc. are listed.

Stein

Stein of Cape Town, South Africa, views anxiety disorders as false alarms. But where does the excess lactate come from? It probably does not come from glucose, which is metabolized too slowly. Lactate can also come from fats and from amino acids. These substances are burned by the brain in an emergency. It is very unlikely that fat is being burned in the brain because fat deposits have been reported in the brain in mental diseases. Thus the answer is probably amino acids.

Bipolar Disorder

In the May 2004 issue of Archives of General Psychiatry a new study was published by Dager et al. This study reported "brain metabolic alterations in medication-free patients with bipolar disorder". They found gray matter lactate and gamma-aminobutyric acid elevations in these patients.

Brain Study

This study was done by psychiatrists including the famous Dr. Andrew Stoll of McLean Hospital. Stoll is famous for advocating natural substances as treatments in mood disorders. Stoll may be the new Linus Pauling of psychiatry. His views are similar to those of the famous Dr. Andrew Weil, who advocates for alternative medicine but also accepts orthodox medicine. Weil, however, is not a psychiatrist.

The PEPSI (spectroscopy imaging) technique was used to study the living brain. This same technique had been used in a previous study on panic disorder. That study showed excess lactate in the brains of patients with panic disorder. This strongly supports earlier work by a Detroit group (Frohman, Gottlieb, etc.). The Detroit group claimed that the excess lactate came from amino acids. If this is true, then a diet low in amino acids should be considered as a treatment. For more information consult my website, which is www.CraigOlson.bizhosting.com.

Neuropathology

In 1897 Alzheimer reported histological alterations in the cerebral cortex of patients with "dementia praecox". In 1925 Funfgeld reported cell loss and reduced tissue volumes in medial thalamic structures. This was confirmed by Baumer in 1954. Later it was confirmed by Treff and Hempel in 1958.

Tikhonov et al

This Russian group found a toxic protein in the blood of schizophrenics. It was a beta-2-globulin. It caused an increased membane permeability in a rat brain assay. Similar results were reported by Romasenko.

Frohman

This brilliant Detroit scientist showed that glucose uptake by cells was diminished by serum from schizophrenics. Utena of Japan reported similar results using cerebral tissue from patients. The cerebral tissue from schizophrenics took up glucose at lower rates than the tissue from controls. This study was reported in 1967, which was a banner year for this type of research.

Frohman found that amino acids, particularly tryptophan, were flooding the cells. This explained why the glucose metabolism was slow. The brain is burning amino acids instead of glucose for fuel. It would seem that a logical treatment would be a diet very low in amino acids, particularly tryptophan. Such a diet was tried with success by Dr. Saleh, an orthomolecular scientist. Saleh wrote "... the results were quite encouraging ..." in 1991.

Hopf (1954)

Hopf reported pathology in the pallidum and striatum in schizophrenia in 1954.

Gray (1982)

Gray suspected the septo-hippocampal system in anxiety. This is similar to the view of the late Dr. Robert Heath, who localized schizophrenia to the septal area. Similarly Averback found pathology in schizophrenia in the septal area in 1981. The early reports, such as those of Funfgeld in 1925, referred to the disease as "dementia praecox". This diagnosis fell from favor after 1925 and was replaced by "schizophrenia".

Malamud (1967)

Malamud reported "psychiatric disorder with intracranial tumors of the limbic system". This supports the view of Heath and of Torrey. Frohman found that amino acids, particularly tryptophan, were flooding the cells. This explained why the glucose metabolism was slow. The brain is burning amino acids instead of glucose for fuel. It would seem that a logical treatment would be a diet very low in amino acids, particularly tryptophan. Such a diet was tried with success by Dr. Saleh, an orthomolecular scientist. Saleh wrote "... the results were quite encouraging ..." in 1991.

Histopathology

In 1972 Miyakawa et al reported "pathological changes" in the brain in schizophrenia in an electron microscopic study. They found cytoplasmic granules, pathology in the myelin sheaths, pathology in the Golgi apparatus, etc. This was just one of many similar studies on the histopathology of schizophrenia. Funfgeld of Germany reported many findings.

Funfgeld

Funfgeld reported "Schwundzellen", a German term for wasting cells. These are diseased cells. They first show disappearance of nissl bodies and later disintegration ofthe whole cytoplasm. Funfgeld's 1927 report was later confirmed by the Vogts. In 1952 C. Vogt and O. Vogt reported similar findings. They reported "cellular affection of consumption". Funfgeld had called it cytolysis. The cells exhibit a reticulated cytoplasm and almost complete disappearance of Nissl bodies.

The Vogts

The Vogts studied 450 brains. These were the controls. Then they studied 51 psychotic brains of which 17 were considered schizophrenic. They described seven phases during which the cellular structures slowly disintegrate. Four of these phases were considered advanced phases of cellular disintegration characteristic of schizophrenia. These advanced phases are encoutered in great number, particularly in catatonia. The Vogts have described alveolar degeneration, lipoid sclerosis, cellular ballooning, etc. The alveolar degeneration was considered to be part ofthe schizophrenic process.

Roizin, Moriarty, and Weil

In 1945 these American scientists reported demyelination in schizophrenia.

Scharenberg & Brown

In 1954 these American workers studied catatonia. They found extensive necrosis with marked reaction of the three types of glia. This appears to disprove the popular but unsound neurodevelopmental theory. Gliosis and necrosis areboth incompatible with a neurodevelopmental disorder. Rather they suggest a toxic factor. The authors felt that there was an intense metabolic disorder.

Hopf

In 1952 at an international conference in Italy, Hopf reported a study of catatonic patients. He found marked tigrolysis and an increase in lipofuscin deposits in the pallidum and striatum, two areas high in dopamine.

Elvidge & Reed

These workers found swelling of oligodendroglia in biopsies. This was found in both schizophrenia and manic-depressive psychosis. They found hypertrophy (enlargement) of astrocytes. They suggested a toxic factor of metabolic origin.

Detengoff

Detenegoff found lesions in young schizophrenics and attributed them to an endotoxic factor.

Papez

In a series of papers (1944, 1949, 1951), Papez & Bateman reported inclusion bodies inthe cytoplasm of nerve cells. Unfortunately Papez died shortly after the last paper. He studied cortical biopsies of 70 schizophrenics.

Hyden & Hartelius

These Swedish workers studied biopsies of the prefrontal cortex in 10 cases of schizophrenia and one case of manic-depressive psychosis. They found a decrease in the nucleotide and nucleoprotein content in mental disease.

My own theory explains many of these findings. My theory is that amino acids are flooding the cells due to the action of a toxic factor. This explains the destruction of the Nissl bodies since these bodies house amino acids. It also explains the reduction in RNA since RNA is used to make proteins from amino acids. The theory also explains the fat vacuoles seen by Cotton (1915), Alzheimer (1913), the Vogts (1952), Averback (1981), Southard, Freeman, etc. The fat is produced from excessive amino acids flooding the cells. It would appear that a diet very low in amino acids should be considered as a treatment.

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 type of mental disease to particular sections of the brain. Alzheimer and Cotton (1915) reported fat-stained cells and deposits.

Conclusions

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.