Abnormal Energy Metabolism in Mental Disease

There is massive evidence that brain energy metabolism is slow in the various forms of mental disease (1, 2, 3, 4, 5, 6, 7, 11). MELAS is a mitochondrial disease with psychiatric symptoms (8). It is treated by coenzyme Q10. However, there is no cure yet, unfortunately.

"There have been at least 19 case reports of patients with mitochondrial disease presenting with symptoms of a psychiatric disorder which in most cases occurred prior to diagnosis of mitochondrial disease (Fattal et al., 2006). Of these cases, five had major depressive disorder, eight had psychosis, one had bipolar disorder, 3 had an anxiety disorder and one had a major personality change. The latter findings suggest the possibility that a mitochondrial deficit is sufficient to trigger one or more psychiatric disorders."

Mark P. Mattson, Marc Gleichmann, and Aiwu Cheng

Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224

The quote is from Ref. 10.

Slow Brain Glucose Metabolism in Psychiatric Disorders

Slow brain glucose metabolism has been reported in various psychiatric disorders (2, 12). Glucose metabolism is vital for proper functioning of the brain.

Tryptophan Metabolism

But what is causing the brain glucose metabolism to be slow? There is a strong theory that tryptophan metabolism is gowing crazy in mental illness. There is hypercatabolism of tryptophan in schizophrenia. Much of the data behind this theory is presented at my website, which is www.CraigOlson.bizhosting.com. I don't make any money at this site, but Bizhosting might. They advertize on my site. This was part of the deal when I got the website for free. It is a huge website, with over a hundred pages. Some of the pages are huge. I put a lot of chemical structures in this website, so I don't feel the need to put them on Gather or Associated Content. It would be duplication. I had to put the name Bizhosting in the URL to get the free sight. You probably could make money at Bizhosting if you were selling something.

I made the site to promote my ideas and to benefit humanity. My more recent articles (13-16) are available free full text on the Internet.

Other Theories

Theories are almost a dime a dozen in psychiatry. I will try to present the best ones. Ref. 17 reports membrane dysfunction in "neuropsychiatric disorders". The authors are neurologists. Ref. 18, also from India, reports hypercatabolism of tryptophan plus abnormal tyrosine metabolism. Ref. 18 is particularly useful because it is available free full text at the journal (Neurology India) website.

"The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport) in the plasma of these patients."

Ravikumar A, Deepadevi KV, Arun P, Manojkumar V, Kurup PA

Department of Neurology, Medical College, Trivandrum, and Metabolic Disorders Research Centre, Puliyarakonam, Trivandrum, India.

The quote is from Ref. 18. This is particularly interesting because there are many serotonin theories in psychiatry. Perhaps the main theory in popularity is that serotonin is supposed to be low! This theory is used to justify SSRI drugs such as Prozac. However, the serotonin was high in this study. The India scientists felt that there was an error in amino acid transport.

Conclusions

More research is needed. A great deal of research has been already done, but the main serotonin theory does not appear to fit the data. More research should also be done on tyrosine metabolism. If tryptophan is indeed flooding the brain cells, this would explain the defective glucose metabolism. The mitochondria could be burning tryptophan instead of glucose to prevent the brain cells from blowing up like balloons and bursting.

But what are the treatments? This author suggests a diet very low in tryptophan. Unfortunately such a diet is not easy. However, the PKU diet is not easy either, and it works for PKU. The PKU diet is very low in phenylalanine, which is another amino acid.

References

1. Dysregulated Mitochondrial Genes and Networks with Drug Targets in Postmortem Brain of Patients with Posttraumatic Stress Disorder (PTSD) Revealed by Human Mitochondria-Focused cDNA Microarrays, Yan A. Su, Jun Wu, Lei Zhang, Qiuyang Zhang, David M. Su, Ping He, Bi-Dar Wang, He Li, Maree J. Webster, Traumatic Stress Brain Study Group, Owen M. Rennert, and Robert J. Ursano, Int J Biol Sci. 2008; 4(4): 223-235. Published online 2008 August 5.

2. 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.

3. 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.

4. 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.

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. Regenold WT, Phatak P, Kling MA, Hauser P. Post-mortem evidence from human brain tissue of disturbed glucose metabolism in mood and psychotic disorders. Mol Psychiatry. 2004;9:731-733.

7. Shao L, Martin MV, Watson SJ, Schatzberg A, Akil H, Myers RM, Jones EG, Bunney WE, Vawter MP. Mitochondrial involvement in psychiatric disorders. Ann. Med. 2008;40:281-295.

8. Shinkai T, Nakashima M, Ohmori O, Terao T, Nakamura J, Hiramatsu N, Hashiguchi H, Tsuji S. Coenzyme Q10 improves psychiatric symptoms in adult-onset mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: a case report. Aust. N. Z. J. Psychiatry. 2000;34:1034-1035.

9. Fattal O, Budur K, Vaughan AJ, Franco K. Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics. 2006;47:1-7.

10. Mitochondria in Neuroplasticity and Neurological Disorders, Mark P. Mattson, Marc Gleichmann, and Aiwu ChengNeuron. Author manuscript; available in PMC 2009 June 8. PMCID: PMC2692277, Published in final edited form as: Neuron. 2008 December 10; 60(5): 748-766.

11. Kato T. Mitochondrial dysfunction as the molecular basis of bipolar disorder: therapeutic implications. CNS Drugs. 2007;21:1-11.

12. Videbech P. PET measurements of brain glucose metabolism and blood flow in major depressive disorder: a critical review. Acta Psychiatrica Scand. 2000;101:11-20.

13. www.associatedcontent.com/article/2110713/advances_in_orthomolecular_psychiatry.html

14. http://www.associatedcontent.com/article/204738/a_look_at_world_psychiatry_toxic_neurons.html

15. www.associatedcontent.com/article/2092969/the_biochemical_approach_to_mental.html

16. www.associatedcontent.com/article/2085461/scientific_approaches_to_mental_health.html

17. Isoprenoid pathway-related membrane dysfunction in neuropsychiatric disorders. Kurup RK, Kurup PA. Int J Neurosci. 2003 Nov;113(11):1579-91.

18. Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders. Ravikumar A, Deepadevi KV, Arun P, Manojkumar V, Kurup PA. Neurol India. 2000 Sep;48(3):231-8.