Stress and Tryptophan

Life stress has been linked to depression (1). It is consideed a risk factor. Combat stress is known to have caused mental illness (PTSD). Experiments on rats have shown that stress can cause insomnia (2). Ref. 3 reports an alteration of hippocampal glutamate function by stress. However, the bulk of the citations I have seen have reported altered tryptophan metabolism.

Tryptophan

Ref. 4 has implicated excessive tryptophan metabolism in irritable bowel syndrome. Ref. 5 reported anxiety in irritable bowel syndrome patients. Acute tryptophan increase worsened the gastrointestinal symptoms.

. Acute tryptophan depletion had no effect on controls. Acute tryptophan increase also had no effect on controls.

Ref. 6 reported increased brain tryptophan metabolism in schizophrenia. This may be a very important finding. Ref. 7 reported abnormal tryptophan metabolism in depression. There are many such reports in the medical literature. Refs. 8 & 9, both by a brilliant Japanese group, are examples. These latter references also link tryptophan metabolism with stress. Stress alters tryptophan metabolism. They also link depression with stress. Stressed rats can be used as a rat model of depression, although this is not a perfect model.

Psychiatric Drugs

Unfortunately psychiatric drugs have been problematic (10). However, this does not mean that all of psychiatry is bad. MindFreedom is too radical. They are antipsychiatry. The problem with antipsychiatry is that they throw out the baby with the bathwater. Much of psychiatric research, but not all of it, is valid. Be suspicious when large amounts of money are involved, as in psychiatric drugs.

Of Rats and Men

Russian scientists stressed rats (11). They then killed the rats and looked at their brains with the electron microscope. Acute neuronal swelling was seen.

"At the ultrastructural level these phenomena were characterized by an increase in the size of the bodies and nuclei of neurons, complete dissociation of polysomes, swelling of some cisterns of the endoplasmatic reticulum and perinuclear space, and destruction of the mitochondria of apical processes." Oĭfa AI, Kleshchnov VN. (11)

The Russians thought that this was similar to the neuropathology in schizophrenia. These results could be explained if one or more amino acids were flooding the neurons. The cisterns of the endoplasmic reticulum house amino acids. Amino acids can enter the mitochondria and can be burned for fuel. The flooding of the neurons with one or more amino acids could be an emergency response of the brain.

Stress

Another tidbit about stress is that catecholamines are released during stress, including adrenaline. However, there is little adrenaline in the brain. It is mostly in the medullas of the adrenal glands. The possibility remains that some unknown chatecholamine could be causing the flooding of the neurons with amino acids. Dopamine is more common in the brain than adrenaline, also called epinephrine. Dopamine has long been suspected in schizophrenia.

The rats used by these Russians were not given psychiatric drugs, so the results cannot be blamed on these drugs. Thus the stressed rats might be considered a rat model of schizophrenia. In schizophrenia there could be a flooding of the neurons with one or more amino acids.

Conclusions

But what are the treatments for these problems? Ref. 12 discusses organic treatments. Psychotherapy and psychosocial rehabilitation are also treatments. Treatments for disorders of tryptophan metabolism, including niacin, are discussed in Ref.13. These disorders are notorious for having psychiatric symptoms. Strangely both too much tryptophan and too little tryptophan present with psychiatric symptoms. Irritable bowel syndrome has too much tryptophan metabolism. Anxiety is seen.

Orthomolecular treatments are suggested. A diet very low in tryptophan supplemented with niacin is suggested. Both fat and sugar increase the transport of tryptophan into the brain. Since there is already too much tryptophan in the brain in stress disorders, this means that both fat and sugar have to be limited. The resulting diet may cause weight loss. A vegan diet, which is high in fiber, is good. Fruits have almost no fat and have good fiber. Vegetables and grains are also on the diet, but whole grains are the best. This diet has side effects. It fights against cancer, heart disease, obesity, and other chronic diseases.

References

1. Brown GW, Bifulco A, Harris TO (1987) Life events, vulnerability and onset of depression: some refinements. Br J Psychiatry 150:30-42

2. Neural circuitry of stress-induced insomnia in rats. Georgina Cano, Takatoshi Mochizuki, and Clifford B. SaperJ Neurosci. Author manuscript; available in PMC 2009 June 9. PMCID: PMC2693213Published in final edited form as: J Neurosci. 2008 October 1; 28(40): 10167-10184. doi: 10.1523/JNEUROSCI.1809-08.2008.

3. Effects of chronic unpredictable stress and methamphetamine on hippocampal glutamate function. Jamie Raudensky and Bryan K. YamamotoBrain Res. Author manuscript; available in PMC 2008 March 2. PMCID: PMC1839858Published in final edited form as: Brain Res. 2007 March 2; 1135(1): 129-135. Published online 2007 January 2. doi: 10.1016/j.brainres.2006.12.002.

4. Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort. Gerard Clarke, Peter Fitzgerald, John F Cryan, Eugene M Cassidy, Eamonn M Quigley, and Timothy G DinanBMC Gastroenterol. 2009; 9: 6. Published online 2009 January 20. doi: 10.1186/1471-230X-9-6.PMCID: PMC2648992

5. Shufflebotham J, Hood S, Hendry J, Hince DA, Morris K, Nutt D, Probert C, Potokar J. Acute tryptophan depletion alters gastrointestinal and anxiety symptoms in irritable bowel syndrome. Am J Gastroenterol. 2006;101:2582-2587.

6. Schwarcz R, Rassoulpour A, Wu HQ, Medoff D, Tamminga CA, Roberts RC. Increased cortical kynurenate content in schizophrenia. Biol Psychiatry. 2001;50:521-530. doi: 10.1016/S0006-3223(01)01078-2.

7. Myint AM, Kim YK, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord. 2007;98:143-151. doi: 10.1016/j.jad.2006.07.013.

8. Stress. 2008;11(3):198-209. A link between stress and depression: shifts in the balance between the kynurenine and serotonin pathways of tryptophan metabolism and the etiology and pathophysiology of depression. Miura H, Ozaki N, Sawada M, Isobe K, Ohta T, Nagatsu T.

9. Changes in brain tryptophan metabolism elicited by ageing, social environment, and psychological stress in mice. Hideki Miura, Norio Ozaki, Tetsuya Shirokawa, Kenichi Isobe. Stress: The International Journal on the Biology of Stress, Jan 2008, Vol. 11, No. 2, Pages 160-169.

10. http://www.psychologytoday.com/blog/obsessively-yours/201001/five-reasons-not-take-ssris

11. [Ultrastructural analysis of the phenomenon of acute neuronal swelling] Oĭfa AI, Kleshchnov VN. Zh Nevropatol Psikhiatr Im S S Korsakova. 1985;85(7):1016-20. Russian.

12. http://www.associatedcontent.com/article/2568821/organic_treatments_in_psychiatry.html?cat=68

13. http://www.associatedcontent.com/article/2729975/disorders_of_tryptophan_metabolism.html?cat=5