Abnormal Aromatic Metabolism in Mental Diseases

Abnormalities of the metabolism of aromatic amino acids have been reported since the Fifties in schizophrenia and in depression (1, 2). A low tryptophan diet was tried with success as a treatment for schizophrenia (2).

Treatments

"The low-TRP diet improved performance on the Stroop Color and Word Test."

Rosse RB, Schwartz BL, Zlotolow S, Banay-Schwartz M, Trinidad AC, Peace TD, Deutsch SI.

Department of Veterans Affairs Medical Center, Washington, D.C. 20422.

This quote is from Ref. 2.

"Interestingly, depressive symptomatology did not emerge on the TRP-deficient diet, despite the lowering of total plasma TRP levels. There were statistically significant improvements noted on objective ratings of the severity of psychotic symptomatology..." Rosse et al (2)

Unfortunately there have been problems with psychiatric drugs (3, 4).

Tryptophan

Abnormalities in tryptophan metabolism have been reported in mental diseases (5).

"In the group of schizophrenic patients it is possible to exactly differentiate a subgroup with similar psycho-pathological symptomatic by means the course of tryptophan." Kitzrow W, Uebelhack R. (5)

The use of 5-hydroxytryptophan as a treatment was a disaster (6).

Nutritional Theories

Nutritional theories abound in psychiatry (7, 8). Ref. 9 reported amino acid abnormalities.

"Compared to healthy controls, unmedicated schizophrenic patients had significantly higher plasma concentrations of taurine, methionine, valine, isoleucine, leucine, phenylalanine, and lysine. Except for taurine, these amino acids share the L-transport system for neutral amino acids." Bjerkenstedt L, Edman G, Hagenfeldt L, Sedvall G, Wiesel FA. (9)

Depression

Depression is discussed in Ref. 10.

"Serum cortisol levels were significantly higher after administration of 5-hydroxytryptophan (5-HTP), 200 mg orally, in unmedicated patients with affective disorders than in controls." Meltzer HY, Perline R, Tricou BJ, Lowy M, Robertson A. (10)

Schizophrenia

Schizophrenia is described in Refs. 11 & 12. Diseases of tryptophan metabolism are notorious for having psychiatric symptoms including pellagra, Hartnup's disease, acute intermittent porphyria, etc. (13). Some of these are treated with niacin, a metabolite of tryptophan.

Ref. 16 reported "hyperserotoninemia". This is a direct contradiction of the serotonin deficiency theory. It means that the serotonin is too high!

"Hyperserotonemia was not associated with reduced liver tryptophan pyrrolase activity or platelet MAO or plasma amine oxidase activities; rather, it may be a consequence of enhanced tissue tryptophan uptake and utilization." Freedman DX, Belendiuk K, Belendiuk GW, Crayton JW. (16)

Dr. Freedman is now deceased, unfortunately.

Conclusions

Conclusions are difficult because of the diversity of the data. However, there appears to be abnormal tryptophan metabolism in both schizophrenia and depression. At one time there was a theory of a toxic indoleamine which was a metabolite of tryptophan. However, this supposed toxic indoleamine has proven to be elusive.

References 17-23 provide more information on these complex subjects. There is also a toxic catecholamine theory, which is a strong one.

References

1. [Erythrocyte membrane transport of amino acid precursors of monoamines in schizophrenic patients. Comparison with depressive patients]

Azorin JM, Bovier P, Widmer J, Tissot R, Jeanningros R.

Encephale. 1992 Sep-Oct;18(5):585-90. French.

2. Effect of a low-tryptophan diet as an adjuvant to conventional neuroleptic therapy in schizophrenia.

Rosse RB, Schwartz BL, Zlotolow S, Banay-Schwartz M, Trinidad AC, Peace TD, Deutsch SI.

Clin Neuropharmacol. 1992 Apr;15(2):129-41.

3. A case of drug-drug interaction involving clozapine.

Goumeniouk AD, Ancill RJ, MacEwan GW, Koczapski AB.

Can J Psychiatry. 1991 Apr;36(3):234-5.

4. L-tryptophan in neuroleptic-induced akathisia.

Kramer MS, DiJohnson C, Davis P, Dewey DA, DiGiambattista S.

Biol Psychiatry. 1990 Mar 15;27(6):671-2.

5. [Tryptophan-loading in schizophrenia and endogenous depression]

Kitzrow W, Uebelhack R.

Psychiatr Neurol Med Psychol (Leipz). 1987 Jan;39(1):32-7. German.

6. L-5-Hydroxytryptophan-induced delirium.

Irwin M, Fuentenebro F, Marder SR, Yuwiler A.

Biol Psychiatry. 1986 Jun;21(7):673-6.

7. The biology of folate in depression: implications for nutritional hypotheses of the psychoses.

Abou-Saleh MT, Coppen A.

J Psychiatr Res. 1986;20(2):91-101. Review.

8. Dietary influences on neurotransmission.

Zeisel SH.

Adv Pediatr. 1986;33:23-47. Review.

9. Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls.

Bjerkenstedt L, Edman G, Hagenfeldt L, Sedvall G, Wiesel FA.

Br J Psychiatry. 1985 Sep;147:276-82.

10. Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. II. Relation to suicide, psychosis, and depressive symptoms.

Meltzer HY, Perline R, Tricou BJ, Lowy M, Robertson A.

Arch Gen Psychiatry. 1984 Apr;41(4):379-87.

11. [Biochemical and physiopathological bases of the study of tryptophan metabolism in schizophrenia]

Dogaru C, Grecu S.

Rev Med Interna Neurol Psihiatr Neurochir Dermatovenerol Neurol Psihiatr Neurochir. 1984 Apr-Jun;29(2):141-50. Romanian.

12. Clinical response of aggressive schizophrenics to oral tryptophan.

Morand C, Young SN, Ervin FR.

Biol Psychiatry. 1983 May;18(5):575-8.

13. Biochemistry of tryptophan in health and disease.

Bender DA.

Mol Aspects Med. 1983;6(2):101-97. Review

14. Cerebrospinal fluid tryptophan and brain atrophy in patients with chronic schizophrenia.

Rimón R, Latvala M, Hyyppä M, Kampman R.

Ann Clin Res. 1982 Jun;14(3):133-6.

15. [Studies of the indolamine metabolism in endogenous psychoses]

Uebelhack R.

Samml Zwangl Abh Geb Psychiatr Neurol. 1982;50:92-100. German.

16. Blood tryptophan metabolism in chronic schizophrenics.

Freedman DX, Belendiuk K, Belendiuk GW, Crayton JW.

Arch Gen Psychiatry. 1981 Jun;38(6):655-9.

17. Middle molecular weight substances and tryptophan in cerebrospinal fluid of schizophrenic patients.

Sperschneider H, Spustova V, Neumann J, Stein G.

Artif Organs. 1981 May;5(2):177-8.

18. www.associatedcontent.com/article/2012172/controversies_in_psychiatry.html
19. www.associatedcontent.com/article/1990392/advances_in_brain_research_psychiatry.html
20. http://www.associatedcontent.com/article/237845/the_link_between_food_allergies_and.html
21. www.associatedcontent.com/article/1932938/disease_biomarkers_in_psychiatry.html
22. www.associatedcontent.com/article/1926322/advocacy_for_mental_health_clients.html
23. www.associatedcontent.com/article/1922710/new_approaches_to_mental_health.html