Introduction
A great deal of research has been done on schizophrenia in the last century. Prior to that it was called "dementia praecox". Griesinger called it "insanity". Griesinger reported positive neuropathology findings in the disease including enlarged ventricles, suggesting tissue loss.
Schizophrenia
This terrible disease is called "metabolic dysperception" by orthomolecular scientists. The purpose of this name is to point out that the disease is caused by metabolic errors. However, the term "metabolic dysperception" is not in common use. Therefore I use the old term "schizophrenia".
There is new genetic evidence that the transmethylation theory, favored by orthomolecular psychiatrists, is correct. This theory was invented in 1952 by Osmond & Smythies. Since that time Smythies has backed off a bit from the theory. Smythies still feels that a toxic factor in the blood causes schizophrenia, but he suspects that it might be similar to melanin. Melanin is a catecholamine metabolite. Neuromelanin comes from dopamine. In the original 1952 paper, DMPEA was supposed to be the toxin. DMPEA is created by methylation, and hence the name of the theory. The methylation is thought to be abnormal in schizophrenia. It is from this theory that Hoffer & Osmond recommended methyl acceptors as treatments. One of these was NAD. This author, Olson, feels that they chose the wrong methyl acceptors. They should have used polyphenols, which are found in the diet. Because all of this nutrition is hard to digest, this article will be written in installments.
Bogus Theories in Psychiatry
Unfortunately this is a vast area, with many false theories. Some of these theories, such as the viral theory and the immunologic theory, have some evidence in favor of them even though they are false. That makes this area very tricky, filled with pitfalls. For example, there is massive evidence for an unknown toxic factor in schizophrenia. Such a toxic factor could possibly be a toxin (presumably internal, or endogenous), a virus, an antibody, etc. Most likely only one of these explanations is correct. There may even be more than one toxic factor.
Neuropathology Data
Some of the evidence used to support a virus theory comes from neuropathology. Studies have reported an excess of glial proliferation, whitch is consistent with the virus theory. Cerebral atrophy has been reported in schizophrenia, as evidenced by enlarged ventricles. Ballooned and disintegrating cells have been commonly described in the cortex.
Abnormal Leukocytes
In 1963 Fessel and Hirata-Hibi reported "abnormal leukocytes in schizophrenia".
Heath
In 1954 R. G. Heath reported localizing schizophrenia to the septal region of the brain using depth electrodes. This caused an immediate sensation. In 1963 Heath edited a book entitled "Serological Fractions in Schizophrenia". Heath expanded on his earlier neurophysiology work and reported "taraxein", a substance found only in schizophrenics. Taraxein was found to be toxic to monkeys and humans. In 1964 Heath recommended "new physiologic treatments in psychiatry". Other workers at Tulane, including Leach and Byers, supported Heath.
Crow
Timothy Crow and his British group published a series of articles reporting an unknown "agent" in the cerebrospinal fluid of schizophrenics and also in the CSF of patients with Huntington's chorea. They tried various tests for a virus, but the toxic factor flunked all tests for a virus. The factor had a "cytopathic" effect on tissue cultures. Most likely the unknown toxic factor is not a virus. It is more likely to be a chemical toxin like mescaline. However, mescaline is an exogenous poison. The unknown factor is an endogenous poison, created in the body or brain. It could be created in one part of the brain and toxic to other parts of the brain.
Giants of Science: Scharenberg & Brown
In 1952 these brilliant scientists from Michigan used a new technique involving a silver carbonate stain to confirm previous work by Alzheimer. Alzheimer reported disintegration of the astroglia in schizophrenia in a series of reports.
Michigan Results
The Michigan group studied biopsy material removed during a lobotomy. The Hortega stain was used. One cell was reported to be "in an advanced state of clasmatodendrosis". The woman's father was a "nervous and tense" individual who suffered from"nervous breakdowns". Neurons were seen in the daughter in "various stages of degeneration". One cell was "necrotic". Another neuron was "reduced to a shadow". The nucleus was destroyed, the intracellular structures were fragmented, and the neurite was hypertrophic (enlarged). "All components of the brain tissue had suffered an extremely severe damage." Axons were hypertrophic (enlarged) and stood out boldly.
Of Molecules and Men
In 1981 Dr. P. B. Applewhite wrote "... molecules determine our behavior." This is very similar to the points of view previously expressed by Linus Pauling in 1968 and by Osmond in 1952. In 1983 Elsa Colby-Morley, Ph.D., reaffirmed this point of view.
Colby-Morley
Colby-Morley wrote an excellent paper in 1983 entitled "An Orthomolecular Approach to Malnutrition and the Brain". This paper was not widely read, but should have been. Orthomolecular nutrition had been advocated by Dr. Abram Hoffer in 1978.
"Some psychiatrists, unfortunately, have been reluctant to accept the idea that brain function is affected by nutrition." Colby-Morley
Williams (1971) had a similar point of view.
"Every tissue of the body is affected by nutrition." Hoffer (1978)
"Cerebral allergy plays a dominant part in a large percentage of mental and emotional disorders." Colby-Morley
Conclusions
Conclusions are difficult but very important. It would appear that there is a terrible metabolic error or errors that cause schizophrenia. The nature of this error is not completely clear, unfortunately. The enlargement of neurons suggests that the neurons may be overeating some macronutrients, even to the point of bursting. A "necrotic" cell is a dying cell.
References
1. www.associatedcontent.com/article/696389/theories_of_orthomolecular_psychiatry.html
2. www.associatedcontent.com/article/693151/schizophrenia_is_organic.html
3. www.associatedcontent.com/article/692861/the_scientific_study_of_schizophrenia.html
4. www.associatedcontent.com/article/679899/the_molecular_and_cellular_pathology.html
5. www.associatedcontent.com/article/679607/world_research_on_schizophrenia.html


Comments: 8
Also there is a 2004 book by Abramson. The book is called "Overdosed America: The Broken Promise of American Medicine." He criticizes "profit-maximizing science" and the "myth of excellence".
Expert Rev Mol Diagn. 2008 Mar;8(2):209-16. Links
Cerebrospinal fluid: identification of diagnostic markers for schizophrenia.
Schwarz E, Bahn S.
Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, UK. es404@cam.ac.uk
Schizophrenia is a complex neuropsychiatric disease but, despite extensive research efforts over the last 100 years, the etiology of this disorder remains elusive. Diagnosis is still based on a subjective, interview-based process, which may not align with the biological underpinnings of the symptoms. This old-fashioned descriptive approach contributes to the low treatment success and impedes early intervention, which is thought to be crucial for successful therapy. Therefore, there is an urgent need to discover biochemical analytes that facilitate an objective and reliable diagnosis. Disease markers might also have utility for tracking treatment success and compliance, as well as the discovery of novel drug targets. For schizophrenia and psychiatric disorders at large, analyzing cerebrospinal fluid (CSF) is an intuitive choice due to its close proximity to the brain and its clinical accessibility in the living patient. Although numerous studies have aimed to identify potential diagnostic markers in the CSF of schizophrenia patients, as yet not one has found its way to clinical application. Here, we review molecular alterations of proteins and metabolites that have been identified in schizophrenia CSF and discuss their potential applicability as diagnostic markers.
Neuro Endocrinol Lett. 2006 Jun;27(3):297-305. Links
CSF-studies in neuropsychiatric disorders.
Raedler TJ, Wiedemann K.
University Hospital Hamburg-Eppendorf, Department of Psychiatry, Martinistr. 52, 20246 Hamburg, Germany. traedler@uke.uni-hamburg.de
Cerebrospinal fluid (CSF) is a clear and colourless fluid that surrounds the brain and spine. Due to the close proximity of CSF to the brain, pathological brain-processes are likely to be reflected in CSF. CSF can be obtained through lumbar puncture and is frequently performed in the differential diagnosis of neuropsychiatric disorders. Beyond clinical applications, CSF has been studied as part of different research-protocols. In this review, we will focus on CSF-analysis in Alzheimer Disease, major depression and schizophrenia. We will review both clinical applications as well as research applications in all three disorders. We will also assess new technological advances that have made it possible to study large numbers of proteins in CSF and how these advances may change CSF-analysis in the years to come.
Annu Rev Clin Psychol. 2008;4:189-216.
Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia.
Walker E, Mittal V, Tessner K.
Department of Psychology, Emory University, Atlanta, Georgia 30322; email: Psyefw@emory.edu , vmittal@mednet.ucla.edu , ktessne@LearnLink.Emory.Edu.
Diathesis-stress models of schizophrenia and other psychotic disorders have dominated theorizing about etiology for over three decades. More recently, with advances in our understanding of the biological processes mediating the effects of stress, these models have incorporated mechanisms to account for the adverse impact of stress on brain function. This review examines recent scientific findings on the role of the hypothalamic-pituitary-adrenal (HPA) axis, one of the primary neural systems triggered by stress exposure, in the expression of vulnerability for schizophrenia. The results indicate that psychotic disorders are associated with elevated baseline and challenge-induced HPA activity, that antipsychotic medications reduce HPA activation, and that agents that augment stress hormone (cortisol) release exacerbate psychotic symptoms. The cumulative findings are discussed in light of a neural diathesis-stress model that postulates that cortisol has the potential to increase activity of dopamine pathways that have been implicated in schizophrenia and other psychotic disorders.
PMID: 18370616 [PubMed - in process]