Valid Theories of Mental Diseases

I have spent a lot of time debunking false theories such as the virus theory and the neurodevelopmental theory. Ref. 1 disproves the neurodevelopmental theory and favors a neurodegenerative theory.

The most popular theory is the dopamine theory (2, 3), which I feel is valid. However, there are several variants of this theory. Methamphetamine has a structure similar to that of certain dopamine metabolites. Mescaline has a chemical structure similar to DMPEA, a toxic dopamine metabolite found only in schizophrenics and in the peyote cactus.

Psychiatric Drugs

Unfortunately psychiatric drugs which act on dopamine have produced terrible side effects, much like a synthetic Parkinson's disease (8, 9). These drugs are called "neuroleptics". Some of the newer drugs act on serotonin. They are called SSRIs (selective serotonin reuptake inhibitors). They also have terrible side effects (including the serotonin syndrome), but the side effects are different.

Marsden (2006)

This UK researcher has written an interesting review of dopamine research (11). The PMC in Ref. 11 probably refers to Pubmed Central, which is where I found the free full text of the document.

"Interestingly, other studies by Daniel Weinberger at NIMH have shown alternative mutations, which decrease COMT activity and so increasing dopamine function in the prefrontal cortex and these individuals show enhanced executive functioning. These findings suggest that COMT inhibitors, such as tolcapone, could help restore normal cognitive functioning in schizophrenia." Marsden (2006)

Parkinson's Disease

Dopamine metabolism is abnormal in Parkinson's disease. An interesting tidbit is that the British doctor Parkinson had the disease himself. He called it the "shaking palsy". Mitochondrial dysfuction has been suspected, possibly due to toxic metabolites. Dopamine and neuromelanin are low. Neuromelanin is a metabolite of dopamine. The drug L-dopa has been used as a treatment.

See Ref. 13 for a discussion of this neurological disease.

COMT and Schizophrenia

There is a very strong theory that COMT is abnormal in schizophrenia (17, 18). This same abnormality has also been suspected in bipolar disorder (18). My own view is that schizophrenia and bipolar disorder are like Tweedledum and Tweedledee.

If COMT is in excesss or is strong to an abnormal degree, then it would appear to make sense to inhibit it. Polyphenols are inhibitors of COMT. Many polyphenols, including flavonoids, are found in the diet. Inhibiting the production of dopamine might be a mistake as it could cause Parkinson's symptoms.

Conclusions

My own theories are explained in great detail in the Associated Content references (19-21). I favor a special diet of all plant foods. Polyphenols are in plant foods. Some plant foods have more of them than others. Flavonoids, a class of polyphenols, are thought to prevent cancer, fight heart disease, prevent cataracts, and do other good things. This diet consists of fruits, vegetables, and grains.

Foods high in flavonoids are given at orthomolecular.org and at worldshealthiestfoods.org. These are outstanding websites. As flavonoids are plant pigments, they are high in brightly colored fruits and vegetables. Carotenoids are also pigments, which is another good reason to eat brightly colored fruits and vegetables. Some carotenoids (beta-carotene, lutein, and xeanthine) are yellow. Lycopene is red.

Green tea is high in polyphenols. Unfortunately it has caffeine, so I drink grape juice and pomegranate juice. I have posted a photo album on Gather which explains flavonoids.

References

1. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis.

Takahashi T, Wood SJ, Yung AR, Soulsby B, McGorry PD, Suzuki M, Kawasaki Y, Phillips LJ, Velakoulis D, Pantelis C.

Arch Gen Psychiatry. 2009 Apr;66(4):366-76.

2. The Dopamine Hypothesis of Schizophrenia: Version III--The Final Common Pathway.

Howes OD, Kapur S.

Schizophr Bull. 2009 May;35(3):549-62. Epub 2009 Mar 26.

3. HORNYKIEWICZ O. A quarter century of brain dopamine research Dopaminergic Systems and their Regulation 1986. London: Macmillan3-18.eds. Woodruff, G.N., Poat, J.A. & Roberts, P.J.

4. AXELROD J. The O-methylation of epinephrine and other catechols in vitro and in vivo. Science. 1957;126:1657-1660.

5. COCHRAN S.M., STEWARD L., KENNEDY M., MCKERCHAR C., PRATT J.A., MORRIS B.J. Induction of metabolic hypofunction and neurochemical deficits after chronic intermittent exposure to phencyclidine: differential modulation by antipsychotic drugs. Neuropsychopharmacology. 2003;28:265-275.

6. LARSEN K.E., FON E.A., HASTINGS T.G., EDWARDS R.H., SULZER D. Methamphetamine-induced degeneration of dopaminergic neurones involves autophagy and upregulation of dopamine synthesis. J. Neurosci. 2002;22:8951-8960.

7. LARUELLE M., ABI-DARGHAM A., VAN DYCK C.H., GIL R., D'SOUSA C.D., ERDOS J., MCCANCE E., ROSENBLATT W., FINGADO C., ZOGHBI S.S., BARDWIN R.M., SEIBYL J.P., KRYSTAL J.H., CHARNEY D.S., INNIS R.B. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc. Natl. Acad. Sci. U.S.A. 1996;93:9235-9240.

8. MARSDEN C.D., JENNER P. The pathophysiology of extrapyramidal side effects of neuroleptics drugs. Psychol. Med. 1980;10:55-72.

9. MARSDEN C.D. TARSY D. BALDESSARINI R.J.Spontaneous and drug-induced movement disorders in psychotic patients Psychiatric Aspects of Neurological Disease 1975. New York: Grune & Stratton219eds. Benson, D.R. & Blumer, D.

10. REYNOLDS G.P. Increased concentrations and lateral asymmetry of amygdala dopamine in schizophrenia. Nature. 1983;305:527-529.

11. Dopamine: the rewarding years
Charles A Marsden
Br J Pharmacol. 2006 January; 147(S1): S136-S144. Published online 2006 January 9. doi: 10.1038/sj.bjp.0706473.
PMCID: PMC1760752

12. ZETTERSTRÖM T., SHARP T., MARSDEN C.A., UNGERSTEDT U. In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after D-amphetamine. J. Neurochem. 1983;41:1769-1773.

13. Computational Systems Analysis of Dopamine Metabolism Zhen Qi, Gary W. Miller, and Eberhard O. VoitPLoS ONE. 2008; 3(6): e2444. Published online 2008 June 18. doi: 10.1371/journal.pone.0002444. PMCID: PMC2435046.

14. Graham DG. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol. 1978;14:633-643.

15. Stokes AH, Hastings TG, Vrana KE. Cytotoxic and genotoxic potential of dopamine. J Neurosci Res. 1999;55:659-665.

16. Napolitano A, Zurcher G, Da Prada M. Effects of tolcapone, a novel catechol-O-methyltransferase inhibitor, on striatal metabolism of L-dopa and dopamine in rats. Eur J Pharmacol. 1995;273:215-221.

17. Is COMT a Susceptibility Gene for Schizophrenia? Hywel J. Williams, Michael J. Owen, and Michael C. O'DonovanSchizophr Bull. 2007 May; 33(3): 635-641. Published online 2007 April 4. doi: 10.1093/schbul/sbm019. PMCID: PMC2526139.

18. Tunbridge EM, Weinberger DR, Harrison PJ. A novel protein isoform of catechol O-methyltransferase (COMT): brain expression analysis in schizophrenia and bipolar disorder and effect of Val158Met genotype. Mol Psychiatry. 2006;11:116-117.

19. www.associatedcontent.com/article/1676885/new_ideas_in_psychiatry.html

20. www.associatedcontent.com/article/1649109/mitochondrial_dysfunction_in_mental.html

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