New Ideas in Psychiatry

Huang et al (Ref. 10) reported "disease biomarkers in cerebrospinal fluid" for "untreated" schizophrenia. If true, this is a significant finding. The authors blame schizophrenia on both genetic and environmental factors, which is true. This is true of a lot of diseases including cardiovascular disease and diabetes. Cardiovascular disease and diabetes are both affected by diet.

"We found highly significant and reproducible differences in samples obtained from first-onset, drug-naïve patients with a diagnosis of paranoid schizophrenia as compared to age-matched controls." Huang et al (2006)

This is an open access article. It is available free full text on the Internet. I found it using Pubmed Central, which is a search engine run by the National Library of medicine. An open access article can be quoted provided the citation is given. The PLoS (Public Library of Science) publishes open access articles. Even the figures can be reproduced provided the citation is given. The PLoS is a very useful organization.

Huang et al (2006)

Some members of this group were from the UK and some were from Germany. Proteins and peptides were studied.

"These schizophrenia-specific protein/peptide changes were replicated in an independent sample set. Both experiments achieved a specificity of 95% and a sensitivity of 80% or 88% in the initial study and in a subsequent validation study, respectively." Huang et al

Three alterations were seen in peptides. This may support Detroit reports of two abnormal proteins in the blood plasma of schizophrenics (20-22). The Detroit group reported that their two proteins were toxic. One was described as a "metabolic" toxin. The Detroit group reported that their toxic factor caused increased tryptophan uptake by cells in an assay. This was later confirmed in the Soviet Union (23, 24).

Neuropathology

There have been many positive contributions in the area of neuropathology, but there have also been false theories. One of the false theories is the virus theory. One of the early pioneers was Dr. Rudolph Virchow of Germany, who favored cellular pathology based on histology. He thought that diseases should be studied at the cellular level. Alzheimer and Nissl followed in his path.

Prof. Thompson and his UCLA group reported progressive brain tissue loss in schizophrenia based on longitudinal studies. This killed the popular, but false, neurodevelopmental theory. Grey matter loss was also seen in Alzheimer's disease. The NMR (nuclear magnetic resonance) technique was used. This enables scientists to see brain tissue loss in living patients.

Gross anatomy studies have shown ventricular enlargement including widening of the temporal horn of the lateral ventricles and reduction of the volume of the amygdala.

Stevens

Prof. Janice Stevens studied the brains of schizophrenics and depressed patients using the PET technique. This technique measures glucose utilization of the brain. Glucose utilization was found to be low in both schizophrenia and depression compared to controls.

Mesa Castillo

Dr. Mesa Castillo of Havana has studied "medial temporal lobe structures including the amygdala, the hippocampus, the parahippocampal gyrus, and the superior temporal gyrus. He started his research in 1977 and has been continuing to the present. Mesa found intranuclear bodies which were unidentified. He suspected that they were a virus. He found membrane alterations. Pathology was seen in the temporal lobes postmortem.

He used elctron microscopy to study schizophrenics and controls. The hippocampus was studied. The brain of the mentally ill has been studied for more than two centuries, but only in the 20th and 21st centuries the electron microscope was available. Previously older techniques such as pneumoencephalography were used. Enlarged ventricles were seen with that technique.

Dr. Mesa studied the amygdala using both optic microscopy and electron microscopy. He found deposits of glycoprotein granules around the vessels in the amygdala. Degenerative changes were seen in the neurons in this nucleus. A microglial reaction was seen around degenerated neurons. Deposits of lipids were seen in degenerated neurons.

PowerPoint Presentations

Mesa has produced PowerPoint presentations which are like computer slide shows. These are available at www.wpanet.org, which is the website of the World Psychiatric Association. He has also published articles at this website.

The COMT Theory

This is a very strong theory (11, 12, 14, 15, 17, 18, 19). The theory is that a genetic error in COMT, which metabolizes dopamine, causes schizophrenia. One variation is that COMT creates a methylated toxin from dopamine. This toxin, thought to be DMPEA, in turn causes tryptophan to flood the brain cells. COMT is inhibited by polyphenols, which are potential treatments.

Conclusions

We seem to be jumping from field to field like a grasshopper, but there are some consistencies in the data. There are also many false theories. One of the most bizarre theories is the radical view of antipsychiatry that mental illness doesn't exist. These radicals deny the existence of schizophrenia, which they feel is just social oppression. They collect disability for it while denying its existence.

Another false theory is the virus theory, favored by Averback (25, 26) and Mesa. Averback found massive bloating and death of neurons in two studies on schizophrenia. These were found in the nucleus ansae peduncularis and in the septal area. SImilar pathology was found in Alzheimer's disease and in Huntington's chorea.

However, Averback's findings were similar to those of Alzheimer (1897, 1913) on "dementia praecox". Averback found that the Nissl bodies were "barely recognizable". He found fat vacuoles. Both of these findings could be explained if amino acids were flooding the cells. Thus Averback's findings were compatible with a metabolic toxin.

There has never been any evidence that schizophrenia is catching. There was once a virus theory for cancer. I don't believe that cancer is catching either. More likely tryptophan is the villain, much like cholesterol is the villain in cardiovascular disease and sugar must be limited in diabetes. A low tryptophan diet is suggested as a treatment.

References

1. Aripiprazole in combination with other antipsychotic drugs may worsen psychosis.J. Adan-Manes and P. Garcia-Parajua.
Journal of Clinical Pharmacy and Therapeutics 34.2 (April 2009): p245(2).

2. http://www.associatedcontent.com/article/1636511/basic_and_applied_research_on_mental.html

3. www.associatedcontent.com/article/1641378/diet_and_schizophrenia.html

4. www.associatedcontent.com/article/1638950/biomarkers_for_schizophrenia.html

5. www.associatedcontent.com/article/1627404/treatments_for_mental_diseases.html

6. Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia Elaine Holmes, Tsz M Tsang, Jeffrey T.-J Huang, F. Markus Leweke, Dagmar Koethe, Christoph W Gerth, Brit M Nolden, Sonja Gross, Daniela Schreiber, Jeremy K Nicholson, and Sabine BahnPLoS Med. 2006 August; 3(8): e327. Published online 2006 August 22. doi: 10.1371/journal.pmed.0030327. PMCID: PMC1551919.

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9. Copy number variations and risk for schizophrenia in 22q11.2 deletion syndrome Anne S. Bassett, Christian R. Marshall, Anath C. Lionel, Eva W.C. Chow, and Stephen W. SchererHum Mol Genet. 2008 December 15; 17(24): 4045-4053. Published online 2008 September 20. doi: 10.1093/hmg/ddn307. PMCID: PMC2638574.

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