Metabolomics: A New Breakthrough in Medicine?

In schizophrenia there is an abnormal metabolic profile (1). The cerebrospinal fluid was studied in drug-naive patients. CSF glucose was found to be abnormal. It was high compared to the controls, suggesting an abnormality in glucose metabolism localized to the brain. Brain glucose metabolism was slow. There appears to be an abnormality in glucoregulatory processes.

Microglial activation has been reported by neuropathologists (2). This is consistent with a metabolic error.

Metabolomics

Ref. 3 explains metabolomics, which can be used for many different diseases including schizophrenia, depression, bipolar disorder, multiple sclerosis, Alzheimer's disease, and other metabolic diseases. It would not be useful for infectious diseases. The idea is to measure a lot of different metabolic parameters and find out which ones come out abnormal. This is kind of a brute force approach to a disease. However, it has yielded useful results so far.

This approach can be used to discover biomarkers for various diseases (4, 5). Ref. 5 calls it "metabonomics", which is an alternate name for the same thing.

Complications

In schizophrenia the drugs can cause metabolic perturbations that are serious (9). Therefore research studies should be done on drug free patients. Another problem with drugs is that drug company research is not all science (10). The results often get fudged. Unwelcome results are not published.

Holmes et al (2006)

This brilliant British report is Ref. 11. Abnormalities were found in glucose, acetate, alanine, and glutamine in the CSF. The glucose was high in schizophrenia in the CSF, but not in the blood serum. This indicates that the metabolic error in glucose metabolism is restricted to the brain. The patients had a kind of diabetes of the brain. The scientists were unable so far to figure out why this is happening.

The pH was lower in the untreated schizophrenics, meaning that their CSF was more acid than the controls. This could be caused by an excess lactic acid or some other acid. An excess of lactic acid can occur when the mitochondria are not functioning well, causing a problem in oxidative energy metabolism.

Amino Acids Flood the Brain Cells

The reason why glucose metabolism is slow in the brain is that it is burning amino acids instead of glucose. But why would it do that?

The answer is that it has to because amino acids are flooding the brain cells. This may also be true in depression, bipolar disorder, Alzheimer's disease, Huntington's chorea, autism, and other neuropsychiatric disorders. If the brain cells weren't burning the excess amino acids, then they could burst. Some of the excess amino acids are being converted to fat.

These matters are discussed in the Associated Content references (13-17), which are free full text. A diet low in protein is suggested as a treatment, but this is not the only possible treatment. A toxin causes these things to happen. Destroying the toxin by oxidation is another possible treatment. Preventing the formation of the toxin (DMPEA) is another possibility.

Conclusions

Metabolomics is the exploration of the metabolome, which is the conglomerate of the biochemicals of the body. Not all diseases are caused by biochemical errors, but many are. Traumas, for example, aren't. However, cancer, heart disease, hypertension, diabertes, and many other diseases are indeed metabolic. Metabolomic investigations are going on in these various diseases.

Some diseases, such as the swine flu, are infectious. Metabolomics would not be useful in these diseases. Nevertheless the verdict is thumbs up for metabolomics.

References

1. "Early treatment of schizophrenia normalizes metabolic profile." Nature Clinical Practice Neurology 2.12 (Dec 2006): 644(1). Health Reference Center Academic. Gale. Newton Free Library. 16 May 2009
http://find.galegroup.com/itx/start.do?prodId=HRCA.

2. Monji, Akira, Takahiro Kato, and Shigenobu Kanba. "Cytokines and schizophrenia: Microglia hypothesis of schizophrenia." Psychiatry and Clinical Neurosciences 63.3 (June 2009): 257(9). Health Reference Center Academic. Gale. Newton Free Library. 16 May 2009
http://find.galegroup.com/itx/start.do?prodId=HRCA.

3. Metabolic Profiling of Patients with Schizophrenia Rima Kaddurah-DaoukPLoS Med. 2006 August; 3(8): e363. Published online 2006 August 22. doi: 10.1371/journal.pmed.0030363. PMCID: PMC1551921.

4. Harrigan GG, Goodacre R. Boston: Kluwer Academic Publishers; 2003. Metabolic profiling: Its role in biomarker discovery and gene function analysis; p. 335. p.

5. Lindon J, Holmes E, Bollard M, Stanley E, Nicholson J. Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis. Biomarkers. 2004;9:1-31.

6. German JB, Roberts MA, Watkins SM. Personal metabolomics as a next generation nutritional assessment. J Nutr. 2003;133:4260-4266.

7. German JB, Hammock BD, Watkins SM. Metabolomics: Building on a century of biochemistry to guide human health. Metabolomics. 2005;1:3-9.

8. Holmes E, Tsang TM, Huang JTJ, Leweke FM, Koethe D. Metabolic profiling of CSF: Evidence that early intervention may impact on disease progression and outcome in schizophrenia. PLoS Med. 2006;3:e327. et al. DOI: 10.1371/journal.pmed.0030327.

9. Meyer J, Koro CE, L'Italien GJ. The metabolic syndrome and schizophrenia: A review. Int Rev Psychiatry. 2005;17:173-180.

10. What Can We Learn from Medical Whistleblowers? Jeanne LenzerPLoS Med. 2005 July; 2(7): e209. Published online 2005 May 27. doi: 10.1371/journal.pmed.0020209. PMCID: PMC1140678.

11. 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.

12. 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.

13. www.associatedcontent.com/article/1728112/mental_illness_and_homelessness.html

14. www.associatedcontent.com/article/1698919/advances_in_biological_psychiatric.html

15. www.associatedcontent.com/article/1680090/cuban_research_on_schizophrenia.html

16. www.associatedcontent.com/article/1680380/the_virus_theory_for_schizophrenia.html

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