Bipolar Disorder: Research Findings

"Prior studies of mRNA expression, protein expression, and pathway metabolite levels have implicated dysregulation of the kynurenine pathway in the etiology of schizophrenia and bipolar disorder."

Miller CL, Murakami P, Ruczinski I, Ross RG, Sinkus M, Sullivan B, Leonard S.

Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21227, USA.

This quote is from ref. 1. The genetic approach to mental diseases has yielded many positive findings, but these findings are not always replicated, unfortunately.

Bipolar Disorder

"Upregulation of the kynurenine pathway has been associated with several etiologies of psychosis, an indication that increased levels of pathway intermediates might be involved in eliciting some psychotic features. In schizophrenia, tryptophan 2,3-dioxygenase (TDO2) was previously identified in postmortem frontal cortex as the enzyme likely responsible for the reported increase in pathway activity in the brain. For this follow-up study of postmortem anterior cingulate gyrus, we have found evidence of increased TDO2 activity in schizophrenia at three different levels of regulation: mRNA, protein, and metabolic product. The results were unaffected by neuroleptic status or smoking history." Ref. 2

They found kynurenine to be high in the brain in both schizophrenia and bipolar disorder. Thus schizophrenia and bipolar disorder may be like Tweedledum and Tweedledee. Knyurenine would be high if tryptophan were flooding the cells.

Bipolar disorder is classified as an affective disorder along with depression and some other disorders. Schizophrenia is not an affective disorder.

A reduction in plasma tryptophan does not necessarily mean a reduction in brain tryptophan. If tryptophan were flooding the cells, this could reduce plasma tryptophan but increase cell tryptophan. But why is all of this important? The anwer is that tryptophan is in the diet. If an error in tryptophan metabolism causes mental disease, then a diet should be considered as a treatment. However, Ref. 3 does not mention this.

Nutritional Treatments

Refs. 4-9 discuss some nutritional treatments. However, Ref. 9 reports a rare case of a bad side effect from a nutritional treatment. Too much vitamin A resulted from excessive fish oil treatment.

Various Theories for Bipolar Disorder (Manic-Depression)

Refs. 10 & 11 explain some of the theories for bipolar disorder. Ref. 12, which is available free full text on the Internet, explains more theories.

Schizophrenia

Ref. 13, also available free full text, explains theories for schizophrenia.

The Drug Companies

Ref. 14 provides information on the ethics of the drug companies.

Conclusions

Further information on mental health is at Refs. 15-17. Ref. 17 explains psychosocial rehabilitation, which is a treatment for bipolar disorder.

My own theory is that amino acids are flooding the brain cells. Since these amino acids are found in the diet, this favors orthomolecular treatment. A diet low in protein is suggested. It is also useful if the diet is high in fiber because fiber, among other things, slows down the rise in blood sugar after eating. Insulin has the effect of pumping tryptophan into the brain. Fiber is also good because it reduces the dietary cholesterol. It also fights against obesity because it has no calories. The vegan diet is suggested because it is high in fiber.

References

1. Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder. Miller CL, Murakami P, Ruczinski I, Ross RG, Sinkus M, Sullivan B, Leonard S. Schizophr Res. 2009 Sep;113(2-3):259-67. Epub 2009 Jun 6.

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

3. 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.

4. Nutr J. 2008 Jan 21;7:2. Nutritional therapies for mental disorders. Lakhan SE, Vieira KF.

5. Wurtman R, O'Rourke D, Wurtman JJ. Nutrient imbalances in depressive disorders. Possible brain mechanisms. Ann N Y Acad Sci. 1989;575:75-82. doi: 10.1111/j.1749-6632.1989.tb53234.x.

6. Young SN. Folate and depression-a neglected problem. J Psychiatry Neurosci. 2007;32:80-82.

7. Hibbeln JR. Fish consumption and major depression. The Lancet. 1998;351:1213. doi: 10.1016/S0140-6736(05)79168-6.

8. Rudin DO. The major psychoses and neuroses as omega-3 essential fatty acid deficiency syndrome: substrate pellagra. Biol Psychiatry. 1981;16:837-850.

9. Grubb BP. Hypervitaminosis A following long-term use of high-dose fish oil supplements. Chest. 1990;97:1260. doi: 10.1378/chest.97.5.1260.

10. Skutsch GM. Manic depression-a disorder of central dopaminergic rhythm. Med Hypotheses. 1981;7:737-746. doi: 10.1016/0306-9877(81)90085-2.

11. Skutsch GM. Manic depression: a multiple hormone disorder? Biol Psychiatry. 1985;20:662-668. doi: 10.1016/0006-3223(85)90101-5.

12. www.associatedcontent.com/article/2245331/affective_illnesses_organic_theories.html

13. www.associatedcontent.com/article/2233855/schizophrenia_as_a_toxic_encephalopathy.html

14. http://libertynewsradio.com/wire/news/2009/09/00228_Merck_employees_had_hit_list_of_doctors_they_sought_to_neutralize_court_documents_reveal_opinion_092025.php

15. www.associatedcontent.com/article/2215925/the_glutamateglutamine_theory_for_schizophrenia.html

16. www.associatedcontent.com/article/2205997/excessive_amino_acids_in_the_brain.html

17. http://www.associatedcontent.com/article/141020/the_fountain_house_standards_are_they.html