Amino Acid Metabolism in Abnormal Psychology

There have been many controversies over the amino acid tryptophan and its metabolites including serotonin, niacin, kynurenine, etc. (1). Kynurenine has been relatively neglected until recently (2). It is now considered neuroactive (1, 2, 3).
Tryptophan and Depression
Depression is thought to be an error in tryptophan metabolism. There are other theories, but the other theories aren't as strong.
Refs. 4-6 give more information on this. There are also theories linking schizophrenia with abnormal tryptophan metabolism (7) and bipolar disorder as well.
Interferon Side Effects
The drug interferon has psychiatric side effects which are thought to be caused by increased tryptophan metabolism (8, 9, 10).

Orthomolecular Theory
"Varying the concentrations of substances normally present in the human body may control mental disease." - Linus Pauling
Pauling, possibly the greatest chemist of all time, published a brilliant article in 1968 (11). He wasn't satisfied with previous treatments in psychiatry, mostly drugs. The quote is from Ref. 11.
"In July 1973 an APA task force of five physicians and one consultant issued a 54-page report titled Megavitamin and Orthomolecular Therapy in Psychiatry (30). In this report the Task Force on Vitamin Therapy in Psychiatry purports to present both theoretical and empirical reasons for completely rejecting the basic concept of orthomolecular psychiatry, which is the achievement and preservation of good mental health by the provision of the optimum molecular environment for the mind, especially the optimum concentrations of substances normally present in the human body." Pauling
I have included Pauling's Ref. 30 as my Ref. 12. Pauling accused the APA of "bias".
Pauling got support from Hoffer, Osmond, and others (13). Pauling's views were similar to those of Roger Williams (14), an advocate for therapeutic nutrition. Williams soon endorsed Pauling's theories.
After a while Pauling moved on to apply his theories to other diseases (15). However, Hoffer carried the torch until his death in 2009. Pauling died in 1994. Hoffer published some of his work on one of his websites (16).
Pauling's theory was so general that it was not restricted to vitamin C, which he favored (in large quantities) for the treatment of cancer. His theory included amino acids, minerals, vitamins, fats ,and diets.
Hoffer
Ref. 17 is one of Hoffer's many books. Ref. 18 supports Hoffer's views. Hoffer placed great importance on niacin, which is an important metabolite of tryptophan.
"In contrast to anti depressant medication I have not yet seen the type of warning issued by Professor Lana Watkins PhD, Duke University, who told the Annual meeting of the American Psychosomatic Society held in Denver, March 4, 2006, that current anti depressants increased the risk of dying from heart disease by 55 percent." Hoffer
The quote is from Ref. 16.
Conclusions
It appears that excessive tryptophan metabolism causes the various forms of mental disease. However, mental retardation is probably a cluster of different diseases. A patient can have both mental illness and mental retardation. Orthomolecular treatment is recommended.
References
1. Tryptophan kynurenine metabolism as a common mediator of genetic and environmental impacts in major depressive disorder: the serotonin hypothesis revisited 40 years later. Oxenkrug GF. Isr J Psychiatry Relat Sci . 2010;47(1):56-63. Review.

2. Lapin IP. Convulsions and tremor in immature rats after intraperitoneal injection of kynurenine and its metabolites. Pharmacol Res Comm. 1978; 10 :81-84.

3. Lapin IP. Neurokynurenines (NEKY) as common neurochemical links of stress and anxiety. Adv Exp Med Biol. 2003; 527 :121-125. [ PubMed ]

4. Oxenkrug GF, Lapin IP. Kynurenine pathway of the metabolism of tryptophan and its possible neuropharmacologic role. In: Yakovelev V, editor.

Chemistry and pharmacology of indole compounds. Kishinev: Stinza; 1975. pp. 5-18.

5. Lapin IP. Antagonism of kynurenic acid to anxiogens in mice. Life Sci. 1998; 63 :PL231-PL236. [ PubMed ]

6. Lapin IP. Kynurenines and anxiety. Adv Exp Med Biol. 1996; 398 :191-194. [ PubMed ]

7. Oxenkrug GF. Tryptophan metabolism as a new target for the treatment of schizophrenia. US Psychiatry Review. 2007:38-39.

8. Widner B, Ledochowski M, Fuchs D. Interferon-gamma-induced tryptophan degradation: Neuropsychiatric and immunological consequences. Curr Drug Metab. 2000; 1 :193-204. [ PubMed ]

9. Capuron L, Miller AH. Cytokines and psychopathology: Lessons from interferon-alpha. Biol Psychiatry. 2004; 56 :819-824. [ PubMed ]

10. Wichers MC, Koek GH, Robaeys G, Verkerk R, Scharpé S, Maes M. IDO and interferon-alpha-induced depressive symptoms: A shift in hypothesis from tryptophan depletion to neurotoxicity. Mol Psychiatry. 2005; 10 :538-544. [ PubMed ]

11. Pauling, L.: Orthomolecular psychiatry. Science 160: 265-271, 1968.

12. Task Force Report 7: Megavitamin and Orthomolecular Therapy in Psychiatry. Washington, DC, American Psychiatric Association, 1973.

13. Hawkins, D., Pauling, L (eds): Orthomolecular Psychiatry; Treatment of Schizophrenia. San Francisco, W.H. Freeman and Co., 1973.

14. Williams, R.J.: Biochemical Individuality. New York, John Wiley & Sons, 1957.

15. Pauling, L: Vitamin C and the Common Cold. San Francisco. W.H. Freeman and Co. 1970.

16. http://www.orthomolecularvitamincentre.com/index.php .

17. Hoffer A: Vitamin B-3 and Schizophrenia: Discovery, Recovery, Controversy. Quarry Press, Kingston, Ont., 2000.

18. Jill James S, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW and Neubrander JA: Metabolic Biomarkers of Increased Oxidative Stress and Impaired Methylation Capacity in Children With Autism. Am J Clin Nutr 2004;80:1611-1617.

19. Hoffer A: Orthomolecular Medicine for Physicians. Keats Pub., New Canaan, CT, 1989.

20. Hoffer A & Osmond H: How To Live With Schizophrenia. University Books, New York, NY,1966. Also published by Johnson, London, 1966.

21. Hoffer A: Chronic schizophrenic patients treated ten years or more. J.Orthomolecular Medicine, 9:7-37,1994.