Introduction
 Lapin of Russia has implicated kynurenine in anxiety (1, 2). This has been supported in the US by Oxenkrug, who is of Russian descent (3). Ref. 3 is a free full text article available on the Internet at Pubmed Central. Ref. 3 is on a high academic level, so knowledge of medical matters is important to reading this brilliant article. The layman would struggle with it. Oxenkrug is a brilliant authority on psychiatry, as is Lapin.
 Kynurenine is the main metabolite of tryptophan, which is found in the diet. Tryptophan is in proteins such as beef, dairy products, etc.
 Lapin of Russia has implicated kynurenine in anxiety (1, 2). This has been supported in the US by Oxenkrug, who is of Russian descent (3). Ref. 3 is a free full text article available on the Internet at Pubmed Central. Ref. 3 is on a high academic level, so knowledge of medical matters is important to reading this brilliant article. The layman would struggle with it. Oxenkrug is a brilliant authority on psychiatry, as is Lapin.
 Kynurenine is the main metabolite of tryptophan, which is found in the diet. Tryptophan is in proteins such as beef, dairy products, etc.
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Psychopathology in Somatic States (Physical Diseases and Drug Side Effects)
 Ref. 4 is an interesting review of work in this area.
"Several somatic illnesses are associated with psychiatric comorbidity. Evidence is provided that availability of the essential amino acid tryptophan, which is the precursor of serotonin, may cause this phenomenon." Russo et al (4)
Down Syndrome
 Down syndrome, which is a form of developmental disability, has been found to have abnormal tryptophan metabolism (5). This shows the tremendous importance of proper tryptophan metabolism. It also suggests that some tryptophan metabolites might be toxic in excess. Since Down syndrome is a brain disease, it appears to show that the brain is vulnerable to increased kynurenine. There is no known effective treatment for Down syndrome, but one study found benefit from vitamins. The government decided not to fund any further studies on this because the study didn't come out the way they wanted it to come out. Pauling blasted the government for this.Â
 Down syndrome, which is a form of developmental disability, has been found to have abnormal tryptophan metabolism (5). This shows the tremendous importance of proper tryptophan metabolism. It also suggests that some tryptophan metabolites might be toxic in excess. Since Down syndrome is a brain disease, it appears to show that the brain is vulnerable to increased kynurenine. There is no known effective treatment for Down syndrome, but one study found benefit from vitamins. The government decided not to fund any further studies on this because the study didn't come out the way they wanted it to come out. Pauling blasted the government for this.Â
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 Linus PaulingÂ
 This photo of Pauling and his family is shown courtesy of the National Library of Medicine. The photo is from 1918.
Cushing's Disease
 This disease was named after a brilliant American neurosurgeon. It is a disease of the endocrine glands. Cushing was interested in it because the pituitary gland is right below the brain.
An excess of adrenal cortex hormones causes psychiatric symptoms (6). The pituitary gland can influence the adrenal glands. Cortisol is known to enhance tryptophan catabolism in the kynurenine pathway, which is the main pathway of tryptophan degradation. The serotonin pathway is a minor pathway.
Pauling
"Varying the concentrations of substances normally present in the human body may control mental disease." - Linus Pauling (1968)
Interferon-Alpha
Interferon-Alpha
 The drug interferon-alpha is known to cause depression as a side effect (7). It is also known to stimulate tryptophan degradation into kynurenine.
Conclusions
Conclusions
 The evidence for tryptophan involvement in behavioral health is simply massive (8-10). What remains to be determined is what to do about it. Ref. 9 points out that diet and dietary components are involved. Tryptophan is indeed in the diet. This is the approach favored by Pauling, Hoffer, and Saul (11).Â
2. Lapin IP. Neurokynurenines (NEKY) as common neurochemical links of stress and anxiety. Adv Exp Med Biol. 2003;527:121-125. [PubMed]
4. Russo S, Kema IP, Fokkema MR, Boon JC, Willemse PH, de Vries EG, den Boer JA, Korf J. Tryptophan as a link between psychopathology and somatic states. Psychosomatic Medicine. 2003;65:665-671. [PubMed]
5. Baran H, Cairns N, Lubec B, Lubec G. Increased kynurenic acid levels and decreased brain kynurenine aminotransferase I in patients with Down syndrome. Life Sci. 1996;58:1891-1899. [PubMed]
6. <cite><cite>Sonino</cite> N, Fava GA, Raffi AR, Boscaro M, Fallo F. Clinical correlates of major depression in Cushing's disease. Psychopathology</cite>CrossRef Medline 1998; 31: 302-6.
7. Symptomatic Treatment of Interferon-?-Induced Depression in Hepatitis C: A Systematic Review. 1992; 67: 127-144.
Baraldi S, Hepgul N, Mondelli V, Pariante CM.
J Clin Psychopharmacol. 2012 Jun 19. [Epub ahead of print]
8. <cite>Sandyk R. L-tryptophan in neuropsychiatric disorders: a review. Int J Neurosci</cite>Medline
<cite>9. Young SN. The use of diet and dietary components in the study of factors controlling affect in humans: a review. J Psychiatry Neurosci 1993; 18: 235-44.</cite> Medline
10. <cite>Bender DA. Biochemistry of tryptophan in health and disease. Mol Aspects Med 1983; 6: 101-97.</cite> CrossRef Medline
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 These images are presented courtesy of Public Domain Clipart.
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Craig Olson
CraigEdwinOlson1@yahoo.com
 These images are presented courtesy of Public Domain Clipart.
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Craig Olson
CraigEdwinOlson1@yahoo.com
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Emanuel Cheraskin, M.D., D.M.D.