Abnormal Tryptophan Metabolism in Psychiatric Diseases

There have been many reports of abnormal tryptophan metabolism in psychiatric diseases and in physical diseases with psychiatric symptoms (1, 2, 3).

"The findings of this study indicate a hyperactive pro-inflammatory response inducing a change in tryptophan metabolism that might be related to the development of positive symptoms in schizophrenia."

Kim YK, Myint AM, Verkerk R, Scharpe S, Steinbusch H, Leonard B.

Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea.

This quote is from Ref. 3.

Irritable Bowel Syndrome

Tryptophan has also been implicated in IBS (4, 5). This is interesting because serotonin is a neurotransmitter in the bowel. Tryptophan is a precursor of serotonin.

Pellagra

Strangely a deficiency of tryptophan also leads to psychiatric symptoms in pellagra (9). This is treated by niacin. The other reports reveal an excess of tryptophan metabolism.

Glutamate Also Suspected

Glutamate is a common neurotransmitter in the brain. Glutamate, another amino acid, has also been suspected (10).

Interferon

Interferon is a drug used to treat cancer (11).

"Immunotherapy with interferon-alpha (IFN-alpha) is associated with psychiatric side-effects, including depression. One of the putative pathways underlying these psychiatric side-effects involves tryptophan (TRP) metabolism. Cytokines including IFN-alpha induce the enzyme indoleamine 2,3-dioxygenase (IDO), which converts TRP to kynurenine (KYN), leading to a shortage of serotonin (5-HT)."

Van Gool AR, Verkerk R, Fekkes D, Bannink M, Sleijfer S, Kruit WH, van der Holt B, Scharpé S, Eggermont AM, Stoter G, Hengeveld MW.

Department of Psychiatry, Erasmus MC, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.

This quote is from Ref.11. tryptophan metabolism is enhanced by interferon, resulting in psychiatric side effects of the treatment.

Prepartum & Postpartum Depression

"Tryptophan was found to be negatively associated with total depression scores in the prepartum, as well. These findings warrant further investigation that could lead to novel interventions to decrease poor outcomes from peripartum depression."

Scrandis DA, Langenberg P, Tonelli LH, Sheikh TM, Manogura AC, Alberico LA, Hermanstyne T, Fuchs D, Mighty H, Hasday JD, Boteva K, Postolache TT.

Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, USA.

This quote is from Ref.12. It would appear that tryptophan has been implicated in almost every type of mental illness that there is!

Conclusions

But what are the treatments? One treatment, niacin, has already been mentioned. I favor the use of therapeutic nutrition, sometimes called orthomolecular psychiatry. Dr. Andrew Weil calls it "integrative medicine". There is a four volume set of new books called "The Gale Encyclopedia of Alternative Medicine, Second Edition". This set of books, although probablvery expensive, can probably be searched at the Gale databases including Health Reference Center. There is also a science Gale database. These valuable databases are usually available at any large library in the US. They include nutrition in this set of books, but the books also include other forms of alternative medicine. This set of books came out in 2005. However, the databases include 2009 work.

I don't consider exercise to be alternative medicine. Yoga is, but neither of these approaches, although healthy, get to the root of the problems in mental illness. Exercise is good for losing weight and for high blood pressure.

Refs. 16-18 provide information on treatments including orthomolecular measures. I favor an orthomolecular diet with supplements. These supplements have good side effects including the prevention of cancer. Fiber slows the rapid rise of blood sugar after you eat. Fiber fights against obesity because it has no calories. Fiber has no tryptophan, nor does water. Water has no calories also. These supplements are much cheaper than drugs.

References

1. Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study. Patkar AA, Rozen S, Mannelli P, Matson W, Pae CU, Krishnan KR, Kaddurah-Daouk R. Psychopharmacology (Berl). 2009 Aug 1. [Epub ahead of print]

2. Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia. Yao JK, Dougherty GG Jr, Reddy RD, Keshavan MS, Montrose DM, Matson WR, Rozen S, Krishnan RR, McEvoy J, Kaddurah-Daouk R. Mol Psychiatry. 2009 Apr 28. [Epub ahead of print]

3. Cytokine changes and tryptophan metabolites in medication-naïve and medication-free schizophrenic patients. Kim YK, Myint AM, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Neuropsychobiology. 2009;59(2):123-9. Epub 2009 Apr 22.

4. 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.

5. Dinan TG, Quigley EM, Ahmed SM, Scully P, O'Brien S, O'Mahony L, O'Mahony S, Shanahan F, Keeling PW. Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology. 2006;130:304-311. doi: 10.1053/j.gastro.2005.11.033.

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. Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort. Clarke G, Fitzgerald P, Cryan JF, Cassidy EM, Quigley EM, Dinan TG. BMC Gastroenterol. 2009 Jan 20;9:6.

9. Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy. Prakash R, Gandotra S, Singh LK, Das B, Lakra A. Gen Hosp Psychiatry. 2008 Nov-Dec;30(6):581-4. Epub 2008 Jul 23.

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. Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-alpha: course and relationship with psychiatric status. Van Gool AR, Verkerk R, Fekkes D, Bannink M, Sleijfer S, Kruit WH, van der Holt B, Scharpé S, Eggermont AM, Stoter G, Hengeveld MW. Psychiatry Clin Neurosci. 2008 Oct;62(5):597-602.

12. Prepartum Depressive Symptoms Correlate Positively with C-Reactive Protein Levels and Negatively with Tryptophan Levels: A Preliminary Report. Scrandis DA, Langenberg P, Tonelli LH, Sheikh TM, Manogura AC, Alberico LA, Hermanstyne T, Fuchs D, Mighty H, Hasday JD, Boteva K, Postolache TT. Int J Child Health Hum Dev. 2008 Aug;1(2):167-174.

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

14. Capuron L, Ravaud A, Dantzer R. Early depressive symptoms in cancer patients receiving interleukin 2 and/or interferon alfa-2b therapy. J Clin Oncol. 2000;18(10):2143-51.

15. Reichenberg A, Yirmiya R, Schuld A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry. 2001;58:445-52.

16. www.associatedcontent.com/article/2163849/the_psychiatric_side_effects_of_drugs.html

17. www.associatedcontent.com/article/2128781/the_biochemical_explanation_for_schizophrenia.html

18. www.associatedcontent.com/article/2137315/abnormal_energy_metabolism_in_mental.html