Abnormal Tryptophan Metabolism in Depression and Other Mental Diseases

Stress can be a factor in various mental diseases.

Depression
There are many different theories of depression (1, 2). Refs. 1 & 2 favor the autoimmune theory, which I believe is wrong. Nevertheless there is value in these reports because of the connection between cytokines and tryptophan. Cytokines increase tryptophan metabolism (1, 2).

Schizophrenia
There are similar theories for schizophrenia (3).
"The immune response in schizophrenia seems to be associated with the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and imbalance in the tryptophan/kynurenine metabolism resulting in increased production of kynurenic acid in the brain." Muller et al (3)
This work was done at the Department of Psychiatry and Psychotherapy Ludwig-Maximilians-University, Nussbaumstr. 7, 80336 MUNICH, Germany. Norbert.Mueller@med.uni-muenchen.de.
Ref. 4 suspects a neurotoxic metabolite of tryptophan in schizophrenia.
"Taken together, our findings suggest a neurotoxic product of tryptophan metabolism, 3-OHKY, predicts severity of clinical symptoms during the early phase of illness and before exposure to antipsychotic drugs." Condray et al (4)
This research was done at the VA Pittsburgh Healthcare System, Medical Research Service, Pittsburgh, PA, USA.
Bipolar Disorder
Tryptophan has also been implicated in bipolar disorder (5). This work was done at the prestigious Karolinska Institute in Stockholm, Sweden. This institute awards the Nobel prizes in medicine.
"Patients with schizophrenia show elevated brain levels of the neuroactive tryptophan metabolite kynurenic acid (KYNA)." Olsson et al (5).
Conclusions
There is a great deal of evidence for excessive tryptophan metabolism in the various psychiatric disorders (6). This could be explained if too much tryptophan was flooding the brain cells. But why would this happen? It could be an emergency respones of the body to stress. These diseases could be perpetual states of stress.
There are many other theories of psychiatric disorders. One theory involves the mitochondria. Supposedly the mitochonria are abnormal and producing too little ATP, which is vital to the brain. ATP stores energy needed for cellular reactions. This is a very strong theory, favored by orthomolecular scientists. This theory could also be valid. It could be that a stress chemical is causing tryptophan, and possibly other amino acids as well, to flood the cells. This could be causing the mitochondria to burn amino acids instead of glucose. The brain depends very heavily on the metabolism of glucose, but it can burn amino acids for fuel in emergencies. It can't burn fat.

A disturbance in brain glucose metabolism could be disastrous to the brain and to proper thinking. This is seen in hypoglycemia, starvation, and certain other situations. It happens if a diabetic takes too much insulin.
More research is needed. These theories add great strength to orthomolecular psychiatry, which has reported abnormal glucose metabolism for decades. Orthomolecular scientists have reported behavioral problems after the ingestion of large amounts of sugar. This causes an increase in brain tryptophan due to a complex mechanism involving insulin. Amino acid transport is affected by insulin.
It could be the increased brain tryptophan that causes the anxiety and other disturbances seen. Orthomolecular scientists have advocated a diet in which sugar is avoided. This is probably a very good idea. Such a diet has been used in diabetes.

More research is needed.

References
1. Raison CL, Capuron L, Miller AH. Cytokines sing the blues : inflammation and pathogenesis of depression. Trends Immunol. 2006; 27 :24-31.

2. Dantzer R, O'Connor JC, Freund GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008; 9 :46-56.

3. Curr Pharm Des. 2011;17(2):130-6. Kynurenine pathway in schizophrenia: pathophysiological and therapeutic aspects. Müller N, Myint AM, Schwarz MJ.

4. Int J Neuropsychopharmacol. 2011 Jan 28:1-12. [Epub ahead of print] 3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia. Condray R, Dougherty GG, Keshavan MS, Reddy RD, Haas GL, Montrose DM, Matson WR, McEvoy J, Kaddurah-Daouk R, Yao JK.

5. J Psychiatry Neurosci. 2010 May;35(3):195-9. Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder. Olsson SK, Samuelsson M, Saetre P, Lindström L, Jönsson EG, Nordin C, Engberg G, Erhardt S, Landén M.

6. Schizophr Bull. 2010 Aug 20. [Epub ahead of print] Increased Levels of Kynurenine and Kynurenic Acid in the CSF of Patients With Schizophrenia. Linderholm KR, Skogh E, Olsson SK, Dahl ML, Holtze M, Engberg G, Samuelsson M, Erhardt S.