Excessive Amino Acids in the Brain in Mental Illness

Kraepelin, a brilliant German psychiatrist, thought that mental illness was caused by "a tanglible morbid process in the brain". He thought that it was caused by "an autointoxication" of the brain. He blamed "dementia praecox", now called "schizophrenia", on a metabolic disturbance.

Fauser supported Kraepelin. Simon of the US rejected Fauser's work. On the other hand, Henry A. Cotton of Trenton in the US favored the autointoxication theory.

A Blood Test for Schizophrenia?

In 2005 a gene-based diagnostic test for schizophrenia was reported by Ming Tsuang in San Diego. They used RNA derived from white blood cells. They also reported a similar test for bipolar disorder. Each disease state had a unique expressed genome signature. They could distinguish between schizophrenics, bipolar disorder patients, and normal controls. This would appear to support Fauser's view. Fauser thought that a blood test was possible.

This is only one of many putative blood tests for schizophrenia. Mesa of Cuba has also proposed a blood test based on microscopic examination of the platelets, which are "gaint" and contain vacuoles and glycogen deposits. I have discussed this at great length in my previous articles because I believe that Mesa's test is valid and useful.

There are also issues of drug side effects causing depression and other psychiatric symptoms (1, 4). Interferon is a drug used to fight cancer and to fight viral diseases.

Interferon

"A better understanding of pathophysiologic mechanisms underlying psychiatric side-effects of IFNalpha is essential to extend access to treatment to some categories of patients that remain excluded from the protocols. A better management of those psychiatric side effects should help the clinician not to draw aside patients at risk, ie patients with depression, drug and alcohol addiction."

Vignau J, Karila L, Costisella O, Canva V. (Ref. 1)

Service d'Addictologie, CHRU de Lille.

In my view much can be learned from this side effect.

"Many psychobehavioural symptoms are observed under IFNalpha treatment. Among them, mood disorders are known to occur early after entry into treatment and to be within the reach of preventive measures." Ref. 1

It seems that interferon causes increased tryptophan metabolism. This is strong support for the tryptophan theory of depression. However, it is not clear whether this supports the serotonin theory. There is a theory that serotonin is supposed to be low in depression. However, diorect postmortem measurements of serotonin in various regions of the brain have debunked that theory. Serotonin was normal in all parts of the brain measured in depression.

Hepatitis C can be caught by intravenous drug abuse.

The tryptophan theory is only one of many amino acid theories in psychiatry (2, 3).

Myelin Abnormalities

Myelin abnormalities have been reported in schizophrenia (3, 6, 7, 8).

The Glutamate Theory

This is a very popular theory in psychiatry (9-13). The number of reports on this theory is quite large.

"The level of glutamine was significantly higher in the left anterior cingulate cortex and thalamus of the patients with schizophrenia than in the healthy subjects."

Théberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, Neufeld RW, Rogers J, Pavlosky W, Schaefer B, Densmore M, Al-Semaan Y, Williamson PC.

Department of Nuclear Medicine and Magnetic Resonance, St Joseph's Health Care, London, On., Canada.

The quote is from Ref. 13, which is particularly useful because it is available free full text at the American Journal of Psychiatry website. Both glutamate and glutamine, close chemical relatives, are found in the diet. A potential treatment would be the restriction of these amino acids in the diet. They are found in wheat gluten and milk products.

Conclusions

This article adds more evidence to previous articles that I have written (14-16). I have only referenced 3 of them because I have written almost 300. This article is another attempt to put the pieces of the jigsaw puzzle together. More than one theory is likely to be true. The tryptophan theory and the glutamate theory could both be true. Tryptophan can make certain nonessential amino acids. Tryptophan itself is an essential amino acid, meaning that it cannot be made from other amino acids.

My articles are available free full text on the Internet. Go to Associated Content and search for them if you want to see more than the ones I have referenced. A diet very low in amino acids is suggested as a treatment. Also fiber supplements are good because they slow the rapid rise in blood glucose after a meal. A rapid rise in blood glucose causes the release of insulin, which pumps more tryptophan into the brain. The brain is already flooded with tryptophan in mental illness.

References

1. Encephale. 2005 May-Jun;31(3):349-57. [Hepatitis C, interferon a and depression: main physiopathologic hypothesis]

2. A new method for rapidly and simultaneously decreasing serotonin and catecholamine synthesis in humans. Marco Leyton, Valerie Kwai Pun, Chawki Benkelfat, and Simon N. Young. J Psychiatry Neurosci. 2003 November; 28(6): 464-467.

3. Brain metabolite abnormalities in the white matter of elderly schizophrenic subjects: implication for glial dysfunction. Linda Chang, Joseph Friedman, Thomas Ernst, Kai Zhong, Nicholas D. Tsopelas, and Kenneth Davis. Biol Psychiatry. Author manuscript; available in PMC 2008 December 15.

4. Goodwin FK, Bunney WE Jr. Depressions following reserpine: a reevaluation. Semin Psychiatry 1971;3:435-48.

5. McCann UD, Penetar DM, Belenky G. Acute dystonic reaction in normal humans caused by catecholamine depletion. Clin Neuropharmacol 1990;13:565-8.

6. Davis K, Stewart D, Friedman J, Buchsbaum M, Harvey P, Hof P, et al. White matter changes in schizophrenia: evidence for myelin-related dysfunction. Archives of General Psychiatry. 2003;60:443-456.

7. Uranova N, Vostrikov V, Orlovskaya D, Rachmanova V. Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophrenia Research. 2004;67:269-275.

8. Hakak Y, Walker J, Li C, Wong W, Davis K, Buxbaum J, et al. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proceedings of the National Academy of Sciences U S A. 2001;98:4746-4751.

9. Javitt DC. Glutamate and Schizophrenia: Phencyclidine, N-Methyl-d-Aspartate Receptors, and Dopamine-Glutamate Interactions. International Review Neurobiology. 2007;78:69-108.

10. Stone JM, Morrison P, Pilowsky LS. Glutamate and dopamine dysregulation in schizophrenia - a synthesis and selective review. Journal of Psychopharmacology. 2007.

11. Coyle JT. Glutamate and schizophrenia: beyond the dopamine hypothesis. Cellular Molecular Neurobiology. 2006;26:365-384.

12. Carter CJ. Schizophrenia susceptibility genes converge on interlinked pathways related to glutamatergic transmission and long-term potentiation, oxidative stress and oligodendrocyte viability. Schizophrenia Research. 2006;86:1-14.

13. Am J Psychiatry. 2002 Nov;159(11):1944-6. Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Théberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, Neufeld RW, Rogers J, Pavlosky W, Schaefer B, Densmore M, Al-Semaan Y, Williamson PC.

14. www.associatedcontent.com/article/2188475/metabolic_problems_in_mental_illness.html

15. www.associatedcontent.com/article/2176981/abnormal_tryptophan_metabolism_in_psychiatric.html

16. www.associatedcontent.com/article/2160239/brilliant_discoveries_in_neuropsychiatry.html