Mitochondrial Dysfunction in Mental Diseases

In this research I have used the website Pubmed Central, which is a government website maintained by the National Library of Medicine. This provides free full text academic articles. Holmes et al (Ref. 10) is one example. These British detectives found impaired brain glucose metabolism in schizophrenia. They found that the cerebrospinal fluid glucose was high.

Tryptophan

Miller et al (13) reported an excess in metabolites of tryptophan in the kynurenine pathway in schizophrenia. This is interesting because tryptophan plays important roles in the brain. It is a precursor of serotonin and also a precursor of niacin.

Nutritional Therapies

References 14 through 24 deal with nutritonal treatments and theories. I do not accept all of these theories, although I feel that some have merit. My experience is that the fish oil treatment does not work and vitamin treatments do not work except in cases of vitamin deficiencies. Similarly, St. John's wort treatment does not work. There is no logical reason why fish oil should work. There is no logical rationale for St. John's wort either.

However, the glutamine theory does tie in with mitochondrial dysfunction. An excess of glutamine could enter the mitochondria and cause a slowing of glucose metabolism. Any glycogenic amino acid could do this if in excess. Tryptophan, if in excess, could do the same thing. The brain would burn the excess tryptophan instead of glucose. Otherwise the mitochondria could burst and the brain cells could burst.

The glutamine theory is presented in Ref. 14. My own theory is that tryptophan floods the brain cells. This explains the excess of tryptophan metabolites found. It also explains why sugar makes matters worse. Sugar triggers insulin, which causes more tryptophan to enter the brain by a complex mechanism. If my theory is correct, and I believe it is, this points towards a nutritional therapy. Schizophrenics may be allergic to tryptophan, much as celiac patients are allergic to glutamine. This is a brain allergy.

The Tryptophan Content of Foods

Tryptophan is in the following foods:

Bananas, beans, brewer's yeast, brown rice bran, caseinate, cottage cheese, dairy products, dates, eggs, fish, lactalbumin, legumes, meat, milk, nuts, peanuts, protein (hydrolysis), seafood, seeds, soy, turkey, whey, whole grains.

Tryptophan in general is in high protein foods such as spinach and most animal products. These foods need to be avoided on a low tryptophan diet. References 1 through 4 give more details on these matters. These are my own articles which are available free full text on Associated Content.

I have also posted slide shows on Gather.com which illustrate these matters. These are also free full text, but you may have to join Gather to read them.

Conclusions

The food allergy theory, advocated by the late Dr. Dohan of Philadelphia, is a good one. He advocated a dairy-free and gluten-free diet. He was worried about a different amino acid (glutamine). My diet is much more severe. My diet also restricts sugar because it triggers the reslease of insulin. This causes amino acids to enter peripheral cells and causes tryptophan to enter the brain.

References

1. www.associatedcontent.com/article/1620292/concepts_of_schizophrenia.html

2. http://www.associatedcontent.com/article/823035/fruits_vegetables_their_value_and_composition.html

3. www.associatedcontent.com/article/1600407/a_review_of_microscopy_studies_of_mental.html

4. www.associatedcontent.com/article/1593193/amino_acids_in_psychiatry.html

5. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, et al. Mitochondrial dysfunction in schizophrenia: Evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 2004;9:684-697. 643.

6. Fernandes J, Berger R, Smit GP. Lactate as energy source for brain in glucose-6-phosphatase deficient child. Lancet. 1982;1:113.

7. Karry R, Klein E, Ben Shachar D. Mitochondrial complex I subunits expression is altered in schizophrenia: A postmortem study. Biol Psychiatry. 2004;55:676-684.

8. Iwamoto K, Bundo M, Kato T. Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum Mol Genet. 2005;14:241-253.

9. Ryan MC, Collins P, Thakore JH. Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry. 2003;160:284-289.

10. 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

11. Neuroanatomical Pattern of Mitochondrial Complex I Pathology Varies between Schizophrenia, Bipolar Disorder and Major Depression Dorit Ben-Shachar and Rachel KarryPLoS ONE. 2008; 3(11): e3676. Published online 2008 November 7. doi: 10.1371/journal.pone.0003676. PMCID: PMC2579333

12. Schizophrenia genomics and proteomics: are we any closer to biomarker discovery? Shaheen E Lakhan and Alon KramerBehav Brain Funct. 2009; 5: 2. Published online 2009 January 7. doi: 10.1186/1744-9081-5-2. PMCID: PMC2627915

13. Miller CL, Llenos IC, Cwik M, Walkup J, Weis S. Alterations in kynurenine precursor and product levels in schizophrenia and bipolar disorder. Neurochem Int. 2008;52:1297-303.

14. Gluten-free diet may alleviate depressive and behavioural symptoms in adolescents with coeliac disease: a prospective follow-up case-series study Päivi A Pynnönen, Erkki T Isometsä, Matti A Verkasalo, Seppo A Kähkönen, Ilkka Sipilä, Erkki Savilahti, and Veikko A AalbergBMC Psychiatry. 2005; 5: 14. Published online 2005 March 17. doi: 10.1186/1471-244X-5-14. PMCID: PMC555756

15. Elevations of Endogenous Kynurenic Acid Produce Spatial Working Memory Deficits Amy C. Chess, Michael K. Simoni, Torey E. Alling, and David J. BucciSchizophr Bull. 2007 May; 33(3): 797-804. Published online 2006 August 18. doi: 10.1093/schbul/sbl033. PMCID: PMC2526148

16. Nutritional therapies for mental disorders Shaheen E Lakhan and Karen F VieiraNutr J. 2008; 7: 2. Published online 2008 January 21. doi: 10.1186/1475-2891-7-2. PMCID: PMC2248201

17. Waring WS. Management of lithium toxicity. Toxicol Rev. 2006;25:221-230. doi: 10.2165/00139709-200625040-00003.

18. Young SN. Clinical nutrition: 3. The fuzzy boundary between nutrition and psycopharmacology. CMAJ. 2002;166:205-209.

19. Wurtman R, O'Rourke D, Wurtman JJ. Nutrient imbalances in depressive disorders. Possible brain mechanisms. Ann N Y Acad Sci. 1989;575:75-82. doi: 10.1111/j.1749-6632.1989.tb53234.x.

20. Young SN. Folate and depression-a neglected problem. J Psychiatry Neurosci. 2007;32:80-82.

21. Hibbeln JR. Fish consumption and major depression. The Lancet. 1998;351:1213. doi: 10.1016/S0140-6736(05)79168-6.

22. Rudin DO. The major psychoses and neuroses as omega-3 essential fatty acid deficiency syndrome: substrate pellagra. Biol Psychiatry. 1981;16:837-850.

23. Rudin DO. The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: substrate beriberi. Med Hypotheses. 1982;8:17-47. doi: 10.1016/0306-9877(82)90088-3.

24. Bell IR, Edman JS, Morrow FD, Marby DW, Mirages S, Perrone G, Kayne HL, Cole JO. B complex vitamin patterns in geriatric and young adult inpatients with major depression. J Am Geriatr Soc. 1991;39:252-257.