Abnormal Amino Acid Metabolism in Schizophrenia and Other Mental Diseases

Proteomics is a relatively new approach to studying diseases (1). This approach looks for abnormal proteins as biological markers. An excess of a normal protein can also be a biological marker.

Positive Findings

Many positive findings have been reported in schizophrenia (2-4). Unfortunately the meanings of some of these findings are not yet clear. In many cases it is not clear whether the abnormality is a basic cause of schizophrenia or merely a side effect of the disease (5).

Nevertheless, the relatively new approach of proteomics seems promising (6).

"The pathological significance of the metabolic and proteomic alterations observed in CSF in first-onset schizophrenia and approx. 33% of the IPS patients require further investigation. As the increase in glucose levels coincides with a decrease in lactate levels in schizophrenia CSF, a possible scenario is that the diseased brain utilizes lactate (which is predominantly produced by astrocytes [14]) instead of glucose as a primary energy source. This has been suggested in a number of pathological conditions such as diabetes and prolonged starvation [15], [16]." Huang JT, Leweke FM, Tsang TM, Koethe D, Kranaster L, Gerth CW, Gross S, Schreiber D, Ruhrmann S, Schultze-Lutter F, Klosterkötter J, Holmes E, Bahn S. (6)

The numers in the quote refer to references in Ref. 6. Ref. 6 is a Public Library of Science publication, meaning that it is an open-access article. This means that it can be extensively quoted provided the citation is given. Further work by this brilliant UK group is given in Refs. 7 & 8.

Diabetes of the Brain?

The energy crisis in the brain in schizophrenia could be a form of diabetes of the brain. The UK results could be explained if amino acids were flooding the brain. The brain might then burn amino acids for fuel instead of glucose. Ref. 9 examines amino acids in schizophrenia.

"Abnormal levels of amino acids have been reported in patients with schizophrenia and have also been investigated as a biomarker to monitor antipsychotic treatment, however results have been inconsistent." Vincenzo De Luca, MD, PhD et al (9)

Ref. 10 reported taurine to be high in drug-free schizophrenics. Ref. 11 found serine to be high in both the serum and blood of schizophrenics. Ref. 12 found hyperasparaginemia in a schizophrenic. This means that arginine was too high in the blood. Ref.13 reported hyperprolinemia in schizoaffective disorder. This means that the amino acid proline was too high in the blood.

Tryptophan

Ref. 14 reports an abnormal gene in schizophrenia and bipolar disorder that is involved with tryptophan metabolism. It was not in the serotonin pathway. Thus the serotonin deficiency theory is not supported.

Proline

Proline is abnormal in an inherited metabolic disease with psychiatric symptoms (15-17). These patients have a cleft palate. The disease goes by various names. One of the names used is the "velo-cardiofacial syndrome" (18). With all of this smoke there is probably a fire (18). In other words, the excess proline appears to be causing the psychiatric symptoms. It appears to poison the brain.

Conclusions

There is massive evidence that the excess of at least one amino acid in the brain can cause psychiatric symptoms. This suggests that schizophrenia may be caused by the excess of one or more amino acids in the brain. This may also be true of other mental disorders. There is evidence linking tryptophan and post traumatic stress disorder (20).

References

1. Lakhan SE. Schizophrenia proteomics: biomarkers on the path to laboratory medicine? Diagn Pathol. 2006;1:11.

2. Coelho FM, Reis HJ, Nicolato R, Romano-Silva MA, Teixeira MM, Bauer ME, Teixeira AL. Increased serum levels of inflammatory markers in chronic institutionalized patients with schizophrenia. Neuroimmunomodulation. 2008;15:140-4.

3. Dietrich-Muszalska A, Olas B. The changes of aggregability of blood platelets in schizophrenia. World J Biol Psychiatry. :1-6. 2007, Sep 14.

4. Dietrich-Muszalska A, Olas B, Rabe-Jablonska J. Oxidative stress in blood platelets from schizophrenic patients. Platelets. 2005;16:386-91.

5. Miyaoka T, Yasukawa R, Yasuda H, Shimizu M, Mizuno S, Sukegawa T, Inagaki T, Horiguchi J. Urinary excretion of biopyrrins, oxidative metabolites of bilirubin, increases in patients with psychiatric disorders. Eur Neuropsychopharmacol. 2005;15:249-52.

6. Huang JT, Leweke FM, Tsang TM, Koethe D, Kranaster L, Gerth CW, Gross S, Schreiber D, Ruhrmann S, Schultze-Lutter F, Klosterkötter J, Holmes E, Bahn S. CSF metabolic and proteomic profiles in patients prodromal for psychosis. PLoS ONE. 2007;2:e756.

7. Huang JT, Leweke FM, Oxley D, Wang L, Harris N, et al. Disease biomarkers in cerebrospinal fluid of patients with first-onset psychosis. PLoS Med. 2006;3:e428.

8. Holmes E, Tsang TM, Huang JT, 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;3:e327.

9. Peripheral Amino Acid Levels in Schizophrenia and Antipsychotic Treatment

Vincenzo De Luca, Emanuela Viggiano, Giovanni Messina, Alessandro Viggiano, Carol Borlido, Andrea Viggiano, and Marcellino Monda. Psychiatry Investig. 2008 December; 5(4): 203-208. Published online 2008 December 31. doi: 10.4306/pi.2008.5.4.203.
10. Bjerkenstedt L, Edman G, Hagenfeldt L, Sedvall G, Wiesel FA. Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls. Br J Psychiatry. 1985;147:276-282.
11. Waziri R, Wilcox J, Sherman AD, Mott J. Serine metabolism and psychosis. Psychiatry Res. 1984;12:121-136.
12. Perry TL, Wright JM, Hansen S. Hyperasparaginemia in a schizophrenic patient. Biol Psychiatry. 1983;18:89-97.
13. Jacquet H, Demily C, Houy E, Hecketsweiler B, Bou J, Raux G, et al. Hyperprolinemia is a risk factor for schizoaffective disorder. Mol Psychiatry. 2005;10:479-485.
14. Two Complex Genotypes Relevant to the Kynurenine Pathway and Melanotropin Function show Association with Schizophrenia and Bipolar Disorder. Christine L. Miller, Peter Murakami, Ingo Ruczinski, Randal G. Ross, Melissa Sinkus, Bernadette Sullivan, and Sherry Leonard. Schizophr Res. Author manuscript; available in PMC 2010 April 16.PMCID: PMC2855687 Published in final edited form as: Schizophr Res. 2009 September; 113(2-3): 259-267. Published online 2009 June 6. doi: 10.1016/j.schres.2009.05.014.
15. Raux G, Bumsel E, Hecketsweiler B, van Amelsvoort T, Zinkstok J, Manouvrier-Hanu S, et al. Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome. Hum Mol Genet. 2007;16:83-91.
16.with deletion (22)(q11.2) syndrome. J Inherit Metab Dis. 2000;23:847-848.
17. Murphy KC, Jones LA, Owen MJ. High rates of schizophrenia in adults withvelo-cardio-facial syndrome. Arch Gen Psychiatry. 1999;56:940-945.
18. Pulver AE, Nestadt G, Goldberg R, Shprintzen RJ, Lamacz M, Wolyniec PS, et al. Psychotic illness in patients diagnosed with velo-cardiofacial syndrome and their relatives. J Nerv Ment Dis. 1994;182:476-478.
19. Shprintzen RJ, Goldberg R, Golding-Kushner KJ, Marion RW. Late onset psychosis in the velo-cardio-facial syndrome. Am J Med Genet. 1992;42:141-142.
20. www.associatedcontent.com/article/2841144/post_traumatic_stress_disorder.html Goodman BK, Rutberg J, Lin WW, Pulver AE, Thomas GH. Hyperprolinaemia in patients