Biomarkers for Schizophrenia

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Holmes et al (Ref.1) studied the cerebrospinal fluid glucose in schizophrenia and found it to be high. This suggests a slowing of brain glucose metabolism. This is a very important finding that has gone laregly unnoticed in the literature except for my own articles. I have lauded it as a brilliant discovery. Ref. 2 adds strengh to this theory. In Ref. 2 schizophrenia is considered a disease of the mitochondria.

The abbreviation PLoS, used in Refs. 1 & 3, means "Public Library of Science". This appears to be a very useful organization.

Genetics

An interesting genetic theory is presented in Refs. 4, 5, and 6. It seems that the enzyme COMT is coded on chromosome 22. This enzyme metabolizes dopamine. This genetic theory fits in with my biochemical theory. My biochemical theory postulates a toxic metabolite of dopamine.

Proline

Proline is an amino acid. There have been a number of reports linking excessive proline to schizophrenia. "Hyperprolinemia" means too much proline in the blood. See Refs. 7-15. The treatment is a diet very low in proline. Since proline is not an essential amino acid, it can be made from other amino acids. Therefore other amino acids should also be restricted. The diet should be a low protein diet.

Proline is in the following foods:

Avocados, beans, brewer's yeast, brown rice bran, caseinate, dairy products, eggs, fish, lactalbumin, legumes, meat, nuts, seafood, seeds, soy, whey, whole grains.

These foods should be avoided. Proline can be synthesized from ornithine and glutamic acid.

COMT

There is a theory that a genetic error in the enzyme COMT causes schizophrenia. See Ref. 16.

Glutamate

There is a glutamate theory for schizophrenia (Ref. 17). This is a very plausible theory because this amino acid is high in the brain and is a neurotransmitter. On top of that, celiac disease, which is a food allergy to wheat gluten and dairy products, presents with psychiatric symptoms.

Conclusions

My own theories are detailed in Refs. 18, 19, and 20. These are free full text articles at Associated Content. I believe that amino acids are flooding the brain cells in mental diseases. In particular I suspect tryptophan. A low protein diet should be tried. Certain vegetables are high in protein including spinach, tofu, mustard greens, crimini mushrooms, soybeans, etc.

References

1. Holmes E, Tsang TM, Huang TJ, Leweke FM, Koethe D, et al. Metabolic profiling of CSF: Evidence that early intervention may impact on disease progression and outcome in schizophrenia. PLoS Med. 2006. doi: 10.1371/journal.pmed.0030327.

2. 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.

3. Disease Biomarkers in Cerebrospinal Fluid of Patients with First-Onset Psychosis Jeffrey T.-J Huang, F. Markus Leweke, David Oxley, Lan Wang, Nathan Harris, Dagmar Koethe, Christoph W Gerth, Brit M Nolden, Sonja Gross, Daniela Schreiber, Benjamin Reed, and Sabine BahnPLoS Med. 2006 November; 3(11): e428. Published online 2006 November 7. doi: 10.1371/journal.pmed.0030428. PMCID: PMC1630717

4. Functional Polymorphisms in PRODH Are Associated with Risk and Protection for Schizophrenia and Fronto-Striatal Structure and Function. Lucas Kempf, Kristin K. Nicodemus, Bhaskar Kolachana, Radhakrishna Vakkalanka, Beth A. Verchinski, Michael F. Egan, Richard E. Straub, Venkata A. Mattay, Joseph H. Callicott, Daniel R. Weinberger, and Andreas Meyer-LindenbergPLoS Genet. 2008 November; 4(11): e1000252. Published online 2008 November 7. doi: 10.1371/journal.pgen.1000252.

5. Karayiorgou M, Morris MA, Morrow B, Shprintzen RJ, Goldberg R, et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci U S A. 1995;92:7612-7616.

6. Lindsay EA, Morris MA, Gos A, Nestadt G, Wolyniec PS, et al. Schizophrenia and chromosomal deletions within 22q11.2. Am J Hum Genet. 1995;56:1502-1503.

7. Pulver AE, Nestadt G, Goldberg R, Shprintzen RJ, Lamacz M, et al. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives. J Nerv Ment Dis. 1994;182:476-478.

8. Murphy KC, Jones LA, Owen MJ. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry. 1999;56:940-945.

9. Ivanov D, Kirov G, Norton N, Williams HJ, Williams NM, et al. Chromosome 22q11 deletions, velo-cardio-facial syndrome and early-onset psychosis. Molecular genetic study. Br J Psychiatry. 2003;183:409-413.

10. Lewis CM, Levinson DF, Wise LH, DeLisi LE, Straub RE, et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet. 2003;73:34-48.

11. Li T, Ma X, Sham PC, Sun X, Hu X, et al. Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population. Am J Med Genet B Neuropsychiatr Genet. 2004;129:13-15.

12. Liu H, Abecasis GR, Heath SC, Knowles A, Demars S, et al. Genetic variation in the 22q11 locus and susceptibility to schizophrenia. Proc Natl Acad Sci U S A. 2002;99:16859-16864.

13. Liu H, Heath SC, Sobin C, Roos JL, Galke BL, et al. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc Natl Acad Sci U S A. 2002;99:3717-3722.

14. Jacquet H, Berthelot J, Bonnemains C, Simard G, Saugier-Veber P, et al. The severe form of type I hyperprolinaemia results from homozygous inactivation of the PRODH gene. J Med Genet. 2003;40:e7.

15. Jacquet H, Demily C, Houy E, Hecketsweiler B, Bou J, et al. Hyperprolinemia is a risk factor for schizoaffective disorder. Mol Psychiatry. 2005;10:479-485.

16. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001;98:6917-6922.

17. Coyle JT. Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell Mol Neurobiol. 2006;26:365-384.

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

19. http://www.associatedcontent.com/article/823035/fruits_vegetables_their_value_and_composition.html
20. www.associatedcontent.com/article/1600407/a_review_of_microscopy_studies_of_mental.html