Searching for the Causes of Mental Diseases

Introduction

Unfortunately there have been a lot of problems with psychiatric drugs including drug interactions (1). Therefore it is of the utmost importance to figure out what is going on in psychiatric diseases. One of the main theories is that schizophrenia is a neurodegenerative disorder (2). There are variations on this theory. One variation is the virus theory. Another variation is the theory that a biochemical toxin causes the disease, a theory that I favor.

The Genetic Approach

There has been no lack of positive findings in this approach (3, 4). Rather the problem is that there have been so many positive findings that it is tedious to try to make sense of the data.

Drug Artifacts

Since psychiatric drugs produce chemical changes (5), unfortunately this can result in artifacts in basic research studies.

Known Physical Diseases with Psychiatric Symptoms

There are a number of known physical diseases which present with psychiatric symptoms including multiple sclerosis (6). In multiple sclerosis neuropathology studies have consistently shown demyelination. This is a loss of the myelin sheaths which cover the axons in white matter in the brain. Similar neuropathology has been reported in the brain in schizophrenia by some researchers. However, it is not as blatant as in MS.

The only definite conclusion that can be made from this is that schizophrenia is a disease of the brain.

Amino Acids

Ref. 7 reported changes in the brain in response to food ingestion. This directly contradicts a popular myth that food has no effect on the brain. People who support this myth have very little knowledge of the brain. Amino acids are very important to the brain. Much of the brain is made up of these amino acids. Also some are neurotransmitters. Others are precursors of neurotransmitters (8).

Ref. 9 appears to implicate tryptophan in depression. Ref. 10 implicates the kynurenine pathway of tryptophan degredation in adolescent depression.

Tryptophan

There has been a great debate as to whether tryptophan is too low or too great in depression (11). It appears to be low in the plasma (11), but is it also low in the brain? The drug interferon, used to fight cancer, causes depression as a side effect (12). This same drug increases tryptophan metabolism.

But how could tryptophan be low in the plasma and high in the brain? This could happen if there was a transport error causing excessive tryptophan to enter the cells. Sherlock Holmes (Sir Author Conan Doyle) said that when you eliminate the impossible, what you have left is the improbable, which is the answer. Doyle was a doctor as well as a writer. My view is that Sherlock Holmes was correct.

Depression

Ref. 13 discusses depression as a side effect of cytokine therapy for cancer. Interferon is a cytokine. The depression appears to have been caused by a change in tryptophan metabolism. The tryptophan appears to have gone from the blood into the cells. British workers have long proposed a disturbance in tryptophan metabolism in depression (14).

Conclusions

There have been many reports connecting abnormal tryptophan metabolism with various forms of mental illness (15, 16). With all of this smoke, it would be amazing if there wasn't a fire. According to Ref. 17, the problem is mainly in the kynurenine pathway, which does not include serotonin. This contradicts the popular serotonin deficiency theory.

Microscopy studies support an error in amino acid metabolism, but Dr. Mesa Castillo favors a virus theory (18). He favors a prenatal origin (in the womb) of schizophrenia. Here the virus strikes, according to his latest theory.

Ref. 19 presents the results of blood studies in mental illness. These studies support a theory of amino acids flooding the cells. Amino acids are found in the diet. This supports orthomolecular treatment.

References

1. www.WorstPills.org.

2. What is schizophrenia: A neurodevelopmental or neurodegenerative disorder or a combination of both? A critical analysis. Gupta S, Kulhara P. Indian J Psychiatry. 2010 Jan;52(1):21-7.

3. Genetic overlap between autism, schizophrenia and bipolar disorder. Carroll LS, Owen MJ. Genome Med. 2009 Oct 30;1(10):102.

4. Whole genome association study in a homogenous population in Shandong peninsula of China reveals JARID2 as a susceptibility gene for schizophrenia. Liu Y, Chen G, Norton N, Liu W, Zhu H, Zhou P, Luan M, Yang
S, Chen X, Carroll L, Williams NM, O'Donovan MC, Kirov G, Owen MJ. J Biomed Biotechnol. 2009;2009:536918. Epub 2009 Oct 27.

5. Possible olanzapine-induced hepatotoxicity in a young Chinese patient. Lui SY, Tso S, Lam M, Cheung EF. Hong Kong Med J. 2009 Oct;15(5):394-6.

6. Early psychiatric manifestation in a patient with primary progressive multiple sclerosis. Shoja Shafti S, Nicknam Z, Fallah P, Zamani L. Arch Iran Med. 2009 Nov;12(6):595-8.

7. Fernstrom JD, Faller DV. Neutral amino acids in the brain: changes in response to food ingestion. J Neurochem. 1978;30:1531-1538.

8. Fernstrom JD. Dietary precursors and brain neurotransmitter formation. Annu Rev Med. 1981;32:413-425.

9. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. J.C. O'Connor, M.A. Lawson, C. André, M. Moreau, J. Lestage, N. Castanon, K.W. Kelley, and R. Dantzer. Mol Psychiatry. Author manuscript; available in PMC 2009 November 1.

10. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Feb 1;34(1):37-44. Epub 2009 Sep 21. The kynurenine pathway in adolescent depression: preliminary findings from a proton MR spectroscopy study. Gabbay V, Liebes L, Katz Y, Liu S, Mendoza S, Babb JS, Klein RG, Gonen O.

11. Anderson IM, Parry-Billings M, Newsholme EA, Poortmans JR, Cowen PJ. Decreased plasma tryptophan concentration in major depression: relationship to melancholia and weight loss. J Affect Disord. 1990;20:185-91.

12. Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, et al. Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment. Biol Psychiatry. 2003;54:906-14.

13. Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry. 2002;7:468-73.

14. Curzon G, Bridges PK. Tryptophan metabolism in depression. J Neurol Neurosurg Psychiatry. 1970;33:698-704.

15. Maes M, Scharpe S, Meltzer HY, Okayli G, Bosmans E, D'Hondt P, et al. Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response. Psychiatry Res. 1994;54:143-60.

16. Maes M, Wauters A, Verkerk R, Demedts P, Neels H, Van Gastel A, et al. Lower serum L-tryptophan availability in depression as a marker of a more generalized disorder in protein metabolism. Neuropsychopharmacology. 1996;15:243-51.

17. Myint AM, Kim YK, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord. 2007;98:143-51.

18. http://www.associatedcontent.com/article/2690467/microscopy_studies_of_mental_illness.html?cat=68

19. http://www.associatedcontent.com/article/2629253/the_role_of_blood_in_mental_illness.html?cat=68