Studies in Scientific Psychiatry

"If we doctors threw all our medicines into the sea, it would be that much better for our patients and that much worse for the fishes." Oliver Wendell Holmes, M.D.

Introduction
Unfortunately all is not science in psychiatry. There is some fudging of the data by drug companies. This is done by selective publication of results. If a drug company doesn't like the way a study comes out, the company makes sure that the study isn't published (1).
Drug Side Effects
There have been controversies over drug side effects (2).
"Antipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism in schizophrenia." Masopust et al (2)
What this means is that blood clots are possible. Ref. 3 reports this also.
"There is an association between use of antipsychotic drugs and risk of venous thromboembolism in a large primary care population. The increased risk was more marked among new users and those prescribed atypical antipsychotic drugs." Parker et al (3)
Ref. 4 reported "hyperlipidemia following treatment with antipsychotic medications".
Biological Markers
Ref. 5 reported plasma protein biomarkers for depression and schizophrenia. Refs. 6 through 10 report positive findings in depression.
Microscopy Studies
Ref. 11 reported abnormal mitochondria in schizophrenia. Ref. 12 reported abnormal platelets in that disease.
Ref. 13 using the electron microscope reported abnormal red blood cells in schizophrenia. These cells were swollen.
Huntington's Chorea
This disease was named after Dr. Huntington of the US who studied it. He found it was hereditary. A famous patient was the late Woodie Guthrie, who died from it. It is a terrible disease of the brain with both psychiatric and neurological symptoms. Guthrie's son Arlo has not caught the disease so far.

A Russian scientist named Lapin has associated both anxiety and epilepsy with tryptophan metabolites (14). He has given these metabolites to rats and mice. They caused the mice to shake and sometimes to have seizures. There is an article in Neurology India that reported abnormal tryptophan metabolism (in excess) in Huntington's chorea and Alzheimer's disease. There is an article on Pubmed that reported tryptophan metabolism in excess in irritable bowel syndrome.
The Metabolic Syndrome
This syndrome can be caused by atypical "antipsychotics" such as Zyprexa, but it can also occur independent of drugs. The patient is shaped like a pear with a lot of fat around the middle. A strict diet is needed.

Conclusions
Stress can precipitate mental illness. This does not fit well with the virus theory for schizophrenia, favored by Dr. Mesa Castillo, a brilliant Havana scientist. Dr. Mesa does have some evidence in favor of his theory (15). For one thing, he has discovered an unknown toxic factor in the cerebrospinal fluid of schizophrenics. However, this could be a metabolic toxin. For another thing, he has found abnormal platelets in schizophrenia (16) that were "giant". These platelets had "elephant feet" and had glycogen deposits. He reported this as a biological test for schizophrenia.

The glycogen deposits appear to suggest a metabolic error in which glucose metabolism is slow. If tryptophan were flooding the platelets, these findings, including vacuoles, would be explained. Tryptophan might be being burned as fuel instead of glucose.

The abnormal platelets are consistent with Ref.12.

Stress fits well with the tryptophan theory. Stress induces changes in tryptophan metabolism increasing rain tryptophan. This was established in rodents by Gerald Curzon and others in the UK.
References
1. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. New England Journal of Medicine. 2008; 358 :252-260. doi: 10.1056/NEJMsa065779. [PubMed] [Cross Ref]
2. BMC Psychiatry. 2011 Jan 3;11:2. Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study.
Masopust J, Malý R, Andrýs C, Vališ M, Bažant J, Hosák L.

3. BMJ. 2010 Sep 21;341:c4245. doi: 10.1136/bmj.c4245. Antipsychotic drugs and risk of venous thromboembolism: nested case-control study.
Parker C, Coupland C, Hippisley-Cox J.

4. Am J Psychiatry. 2006 Oct;163(10):1821-5. Hyperlipidemia following treatment with antipsychotic medications. Olfson M, Marcus SC, Corey-Lisle P, Tuomari AV, Hines P, L'Italien GJ.

5. PLoS One. 2010 Feb 11;5(2):e9166. Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections. Domenici E, Willé DR, Tozzi F, Prokopenko I, Miller S, McKeown A, Brittain C, Rujescu D, Giegling I, Turck CW, Holsboer F, Bullmore ET, Middleton L, Merlo-Pich E, Alexander RC, Muglia P.

6. Connor TJ, Leonard BE. Preskorn SH, Feighner JP, Stanga C, Ross R, editors. Biological markers for Depression. 2004. pp. 117-148. Handbook of Experimental Pharmacology. Antidepressants. Past, Present and Future (Volume 157). Springer, New York.

7. Domenici E, Muglia P. The search for peripheral markers in psychiatry by genomic and proteomic approaches. Exp Opin Med Diagn. 2007; 1 :235-251.

8. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006; 27 :24-31. [PubMed]

9. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009; 65 :732-741.

10. Simon NM, McNamara K, Chow CW, Maser RS, Papakostas GI, et al. A detailed examination of cytokine abnormalities in Major Depressive Disorder. Eur Neuropsychopharmacol. 2008; 18 :230-233. [PMC free article] [PubMed]

11. Perturbation in Mitochondrial Network Dynamics and in Complex I Dependent Cellular Respiration in Schizophrenia. Rosenfeld M, Brenner-Lavie H, Ari SG, Kavushansky A, Ben-Shachar D. Biol Psychiatry . 2011 Mar 10. [Epub ahead of print]

12. Agressologie. 1973 Aug;14(4):275-9. [Abnormal thrombocytes in schizophrenia: electron microscopy observation]. [Article in Spanish] Xalabarder C.

13. Klin Lab Diagn. 2001 Apr;(4):43-6. [Surface relief of peripheral blood erythrocytes in patient with schizophrenia (scanning electron microscopy data)].

[Article in Russian] Novitskiĭ VV, Riazantseva NV, Antonenko NM, Semin IR, Agarkov AP, Mikhalenko VV, Smirnova AV, Mel'nikova AP.

14. Adv Exp Med Biol. 2003;527:121-5. Neurokynurenines (NEKY) as common neurochemical links of stress and anxiety. Lapin IP.

15. www.wpa.net.