Abnormal Tryptophan Metabolism in Depression

There is a view that Abraham Lincoln had "melancholia", which was an old term for depression. Winston Churchill's son Randolph thought that his Father had bipolar disorder, which is a close relative to depression.

There are different amino acid theories involving depression (1, 2). Ref. 1 implicates glutamine. Ref. 2 implicates tryptophan.

The Glutamine Theory

This is a food allergy theory. According to this theory, people with depression may be allergic to glutamine in the diet. Ref. 1, which is from Helsinki, Finland, supports this theory. The theory was once proposed for schizophrenia by Dr. Dohan of Philadelphia. It seems that psychiatric symptoms are seen in celiac disease, which is treated by a gluten-free diet (3, 4). These symptoms are alleviated by the diet. However, Ref. 5 reports that anxiety is reduced but not depression. This appears to suggest that perhaps glutamine may not be the only amino acid involved. The diet is a low glutamine diet.

In celiac disease there is abnormal transport of glutamine in the intestines (6). Glutamate is an important neurotransmitter in the brain (7). Ref. 8 favors the use of pyridoxine, which is a B vitamin.

Psychiatric Drugs

Unfortunately drugs can cause birth defects (8). But are they effective? This matter has been hotly debated. The drug companies say that they are.

Tryptophan

Ref. 9 and a number of other citations have reported abnormalities in tryptophan metabolism in depression. There are so many such citations that I will not be able to list them all. There are also many claims of abnormal tryptophan metabolism in schizophrenia and other psychiatric disorders. Ref. 10 reports a side effect of interferon treatment. This cancer drug causes depression as a side effect. The mechanism involves the activation of a key enzyme that metabolizes tryptophan in the kynurenine pathway. This fact supports some theories for tryptophan metabolism as causing depression. The metabolism appears to be in excess.

Ref. 2 reported an abnormality in the kynurenine pathway in adolescent depression. Stress

Ref. 12 reports a link between stress and depression. This brilliant report is from Japan, as is Ref.13, which reports similar findings. Ref. 2 and Ref. 12 report that certain metabolites of tryptophan in the kynurenine pathway are neurotoxic. Ref. 2 feels that these neurotoxic meabolites may cause depression.

A similar theory was proposed for schzophrenia by neurologists from India. These neurologists found hypercatabolism of tryptophan in "neuropsychiatric" diseases. However, there is a deficiency of metabolites in the kynurenine pathway in acute intermittent porphyria, which has psychiatric symptoms. In porphyria there is an excess of tryptophan because the kynurenine pathway is blocked due to the lack of the first enzyme in this pathway. Serotonin is not deficient in porphyria because the serotonin pathway is overloaded. This throws cold water on the serotonin deficiency theory.

Conclusions

Refs. 14 and 15 provide information on schizophrenia, which also appears to be a disease of tryptophan metabolism. Other amino acids might be involved as well. In celiac disease the psychiatric symptoms are alleviated by a diet low in glutamine. Since it appears that depression involves a flooding of the brain cells with tryptophan, a low tryptophan diet is suggested as a treatment. This diet must be supplemented with niacin to avoid pellagra.

Since the vegan diet is relatively low in tryptophan, it may be a good starting point for experimentation. Corn is very low in tryptophan.

References

1. Gluten-free diet may alleviate depressive and behavioural symptoms in adolescents with coeliac disease: a prospective follow-up case-series study. Päivi A Pynnönen, Erkki T Isometsä, Matti A Verkasalo, Seppo A Kähkönen, Ilkka Sipilä, Erkki Savilahti, and Veikko A AalbergBMC Psychiatry. 2005; 5: 14. Published online 2005 March 17. doi: 10.1186/1471-244X-5-14.

2. The Kynurenine Pathway in Adolescent Depression: Preliminary Findings from a Proton MR Spectroscopy Study. Vilma Gabbay, Leonard Liebes, Yisrael Katz, Songtao Liu, Sandra Mendoza, James S. Babb, Rachel G. Klein, and Oded Gonen. Prog Neuropsychopharmacol Biol Psychiatry. Author manuscript; available in PMC 2010 February 2. PMCID: PMC2815014Published in final edited form as: Prog Neuropsychopharmacol Biol Psychiatry. 2010 February 1; 34(1): 37. Published online 2009 September 21. doi: 10.1016/j.pnpbp.2009.09.015.
3. Holmes GKT. Non-malignant complications of coeliac disease. Acta Paediatr. 1996. pp. 68-75.
4. Ciacci C, Iavarone A, Mazzacca G, De Rosa A. Depressive Symptoms in Adult Coeliac Disease. Scand J Gastroenterol. 1998;33:247-250. doi: 10.1080/00365529850170801.
5. Addolorato G, Capristo E, Ghittoni G, Valeri C, Masciana' R, Ancona C, Gasbarrini G. Anxiety But Not Depression Decreases in Coeliac Patients After One-Year Gluten-free Diet: A Longitudinal Study. Scand J Gastroenterol. 2001;36:502-506.
6. Pynnönen P, Isometsä E, Aronen E, Verkasalo M, Savilahti E, Aalberg V. Mental disorders in adolescents with celiac disease. Psychosomatics. 2004;45:325-335. doi: 10.1176/appi.psy.45.4.325.
7. Hernanz A, Polanco I. Plasma precursor amino acids of central nervous system monoamines in children with coeliac disease. Gut. 1991;32:1478-481.
8. Hallert C, Åström J, Walan A. Reversal of Psychopathology in Adult Coeliac Disease with the Aid of Pyridoxine (Vitamin B6). Scand J Gastroenterol. 1983;18:299-304.

9. Perinatal depression: treatment options and dilemmas. Teri Pearlstein. J Psychiatry Neurosci. 2008 July; 33(4): 302-318.

10. Anderson IM, Parry-Billings M, Newsholme EA, Poortmans JR, Cowen PJ. Decreased plasma tryptophan concentration in major depression: relationship to melancholia and weight loss. J Affect Disord. 1990;20:185-91.
11. Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, et al. Interferon-alpha-induced changes in tryptophan metabolism. relationship to depression and paroxetine treatment. Biol Psychiatry. 2003;54:906-14.
12. 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.
13. Changes in brain tryptophan metabolism elicited by ageing, social environment, and psychological stress in miceHideki 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.
14. http://www.associatedcontent.com/article/2690467/microscopy_studies_of_mental_illness.html?cat=68

15. http://www.associatedcontent.com/article/2629253/the_role_of_blood_in_mental_illness.html?cat=68