Advances in Biochemical Psychiatry

"Science is the search for truth-it is not a game in which one tries to beat his opponent, to do harm to others." Linus Pauling (1958)

Drugs "The weller you are the more drugs you can take without getting sick. That's why doctors don't get into more trouble than they do with therapy." Eugene Stead Jr., 1968 (Believe it or not, this came from the American College of Physicians website! C. O.)

Introduction

The authors William T. Regenold, Pornima Phatak, Christopher M. Marano, Amritpal Sassan, Robert R. Conley and Mitchel A. Kling published a report in March, 2009 (Ref. 5) in which they found elevated lactate in the cerebrospinal fluid in both schizophrenia and bipolar disorder. These scientists suggested that this reflected abnormal mitochondrial function as this finding is seen in mitochondrial diseases. This fits in with my own theory of amino acids flooding the brain cells. It also appears to confirm some Detroit work by Frohman and Gottlieb in the Seventies. The Detroit workers found excess lactate in an assay using plasma from schizophrenics.

Psychiatric Drugs

Unfortunately these drugs have been problematic (Ref. 6 & 7). My own theory is that the approach of orthomolecular psychiatry is more promising.

Erhardt S, Olsson SK, Engberg G

These scientists are from the Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. This prestigious institute awards the Nobel prizes in medicine. They have reported an error in tryptophan degredation in schizophrenia.

"It is also suggested that kynurenines participate in the pathophysiology of psychiatric disorders. Thus, elevated levels of KYNA have been found in the CSF as well as in the post-mortem brain of patients with schizophrenia." Erhardt et al (2009)

See Ref. 9. This report is consistent with my own theory of amino acids flooding the brain cells in schizophrenia.

Muller (2008)

Muller is from the Ludwig-Maximilians-University, Hospital for Psychiatry and Psychotherapy, Nussbaumstr 7, 80336 Munich, Germany.

"Increased levels of kynurenic acid (KYN-A), an endogenous NMDA receptor antagonist, resulting from disturbed tryptophan/kynurenine metabolism can explain psychotic symptoms and cognitive deterioration." Muller (Ref. 10)

Tryptophan Floods the Brain Cells

These findings do not appear to be a drug artifact because chronic neuroleptic administration to rats produces the opposite effect according to Ref. 15. Detroit work done in the Sixties and Seventies by Frohman, Gottlieb, Beckett, and others indicated that a toxic factor in the blood plasma in schizophrenia causes tryptophan, 5-hydroxytryptophan, and alanine to flood the cells in an assay. This is consistent with my theory of amino acids flooding the brain cells in schizophrenia.

Fessel et al (1965)

This group reported abnormal lymphocytes in schizophrenia. See Ref. 18. This finding is consistent with my theories. The Russians have consistently reported a toxic factor in the blood of schizophrenics (ref. 20). This supports my theories and the Detroit work, which is similar.

But What Is the Treatment?

This is the billion dollar question. However, the answer may save massive amounts of money. My view is that a diet low in amino acids, particularly tryptophan and alanine, makes sense as a treatment. For some unknown reason the Detroit workers did not think of this. They were looking for an "antifactor", which was supposed to destroy the toxic plasma factor that they called the "S-protein". Here "S" is short for "schizophrenia". They found an antifactor, which they claimed was a tripeptide. It was called TVL for the three amino acids in it (threonine, valine, and leucine). However, one of the main researchers died and another retired. It appears to have never been approved by the Food & Drug Administration.

Conclusions

Alanine is in the following foods:

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

Tryptophan is in the following foods:

Bananas, beans, brewer's yeast, brown rice bran, caseinate, cottage cheese, dairy products, dates, eggs, fish, lactalbumin, legumes, meat, milk, nuts, peanuts, protein (hydrolysis), seafood, seeds, soy, turkey, whey, whole grains.

The diet is a low protein diet. Since coenzyme Q10 is healthy for the heart, and since this vitamin is made from tyrosine, an amino acid, those on a low protein diet might do well to take coenzyme Q!0 as a supplement. I have taken this supplement without any adverse effects.

References

1. www.associatedcontent.com/article/1520081/the_neurochemistry_of_mental_diseases.html

2. www.associatedcontent.com/article/1506969/a_review_of_scientific_studies_of_mental.html

3. www.associatedcontent.com/article/1485724/a_hypothesis_for_mental_disease.html

4. www.associatedcontent.com/article/1496620/mental_illness_perspectives_including.html

5. Regenold, William T., Pornima Phatak, Christopher M. Marano, Amritpal Sassan, Robert R. Conley, and Mitchel A. Kling. "Elevated Cerebrospinal Fluid Lactate Concentrations in Patients with Bipolar Disorder and Schizophrenia: Implications for the Mitochondrial Dysfunction Hypothesis.(Report)." Biological Psychiatry 65.6 (March 15, 2009): 489(6). Health Reference Center Academic. Gale. Needham Free Public Library. 11 Mar. 2009
http://find.galegroup.com/itx/start.do?prodId=HRCA.

6. Add-on filgrastim during clozapine rechallenge in patients with a history of clozapine-related granulocytopenia/agranulocytosis.

Joffe G, Eskelinen S, Sailas E.

Am J Psychiatry. 2009 Feb;166(2):236.

7. Aasly J, Sando S, Undeland M, Waage A.

Tidsskr Nor Laegeforen. 2009 Jan 1;129(1):33-5. Norwegian.

8. New promises for manipulation of kynurenine pathway in cancer and neurological diseases.

Costantino G.

Expert Opin Ther Targets. 2009 Feb;13(2):247-58.

9. Pharmacological manipulation of kynurenic Acid: potential in the treatment of psychiatric disorders.

Erhardt S, Olsson SK, Engberg G.

CNS Drugs. 2009;23(2):91-101. doi: 10.2165/00023210-200923020-00001.

10. Inflammation and the glutamate system in schizophrenia: implications for therapeutic targets and drug development.

Müller N.

Expert Opin Ther Targets. 2008 Dec;12(12):1497-507. Review.

11. Elevated levels of kynurenic acid change the dopaminergic response to amphetamine: implications for schizophrenia.

Olsson SK, Andersson AS, Linderholm KR, Holtze M, Nilsson-Todd LK, Schwieler L, Olsson E, Larsson K, Engberg G, Erhardt S.

Int J Neuropsychopharmacol. 2008 Sep 17:1-12. [Epub ahead of print]

12. Kynurenine pathway in psychosis: evidence of increased tryptophan degradation.

Barry S, Clarke G, Scully P, Dinan TG.

J Psychopharmacol. 2008 Jun 18. [Epub ahead of print]

13. Alterations in kynurenine precursor and product levels in schizophrenia and bipolar disorder.

Miller CL, Llenos IC, Cwik M, Walkup J, Weis S.

Neurochem Int. 2008 May;52(6):1297-303. Epub 2008 Feb 2.

14. Tryptophan breakdown pathway in bipolar mania.

Myint AM, Kim YK, Verkerk R, Park SH, Scharpé S, Steinbusch HW, Leonard BE.

J Affect Disord. 2007 Sep;102(1-3):65-72. Epub 2007 Jan 30.

15. Chronic neuroleptic treatment reduces endogenous kynurenic acid levels in rat brain.

Ceresoli-Borroni G, Rassoulpour A, Wu HQ, Guidetti P, Schwarcz R.

J Neural Transm. 2006 Oct;113(10):1355-65. Epub 2006 Feb 9.

16. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder.

Miller CL, Llenos IC, Dulay JR, Weis S.

Brain Res. 2006 Feb 16;1073-1074:25-37. Epub 2006 Jan 30.

17. Globulins and behavior in schizophrenia.

Solomon GF, Moos RH, Fessel WJ, Morgan EE.

Int J Neuropsychiatry. 1966 Feb;2(1):20-6.

18. Genetic and stress factors affecting the abnormal lymphocyte in schizophrenia.

Fessel WJ, Hirata-Hibi M, Shapiro IM.

J Psychiatr Res. 1965 Dec;3(4):275-83.

19. ABNORMAL LEUKOCYTES IN SCHIZOPHRENIA.

FESSEL WJ, HIRATA-HIBI M.

Arch Gen Psychiatry. 1963 Dec;9:601-13.

20. Act Nerv Super (Praha). 1972;14(2):137-8.

The effect of schizophrenic plasma on tissue culture. Naneishvili BR, Zurabashvili ZA, Eliava LA, Darchia NS.Hoffer favors treatment with niacin (vitamin B3). Although safe, my experience is that this does not work for schizophrenia, although it does work for pellagra.