Abnormal Tryptophan Metabolism in Psychiatric Diseases

Some useful information can be obtained about schizophrenia from the International Schizophrenia Foundation, 16 Florence Avenue, Toronto, Ontario, Canada M2N 1E9. Fax (416) 733-2352. There is also a lot of very useful information at Gather and at Associated Content. I have written the equivalent of several books at both of these sites.

Tryptophan Metabolism

Ref. 1 reported that a stress hormone induces increased tryptophan metabolism. Refs. 2 & 3 reported abnormal tryptophan metabolism in mental disesases. Ref. 3 is from the prestigious Karolinska Institute in Stockholm, Sweden. This institute awards the Nobel prizes in medicine.

Bipolar Disorder

Bipolar disorder is discussed in Ref. 4. Ref. 5 reports genetic similarities between bipolar disorder and schizophrenia. This suggests that the chemical pathology may be similar. Ref. 6 blames bipolar disorder on abnormal dopamine metabolsm, which is the main theory for schizophrenia. This does not mean that the tryptophan theory is wrong. An error in dopamine metabolism could cause an error in tryptophan metabolism. Dopamine is tremendously important in the brain.

Schizophrenia

Ref. 7 reported abnormal (excessive) metabolism of tryptophan in schizophrenia. Ref. 8 confirmed Ref. 7. Ref. 9 reported excessive tryptophan metabolism in the brain in schizophrenia. With all of this smoke, there must be a fire.

Psychotic Symptoms in HIV

Ref. 10 has implicated excessive tryptophan metabolism in HIV psychosis.

Are Schizophrenia and Bipolar Disorder Points on a Continuum?

Ref. 11 appears to support the theory that schizophrenia and bipolar disorder are closely related. The diagnosis may be like ladies' fashions. One diagnosis might be in fashion with psychiatrists in the UK, and another diagnosis might be in fashion with psychiatrists in the US.

Conclusions

But what are the treatments? The answer may be orthomolecular treatments. It is possible that other amino acids may be involved in addition to tryptophan. The data would be explained if tryptophan were flooding the brain cells.

The disease AIP (acute intermittent porphyria) is associated with psychiatric symptoms caused by too much tryptophan poisoning the brain. The reason why this happens is that there is a block in the kynurenine pathway of tryptophan metabolism. This causes a buildup of tryptophan and shunting of it into the serotonin pathway. Thus there may be excessive serotonin. This does not support the serotonin deficiency theory of depression advocated by the drug companies.

My view is that a diet very low in tryptophan should be tried. Such a diet should be supplemented by niacin so as to avoid niacin deficiency because niacin is a metabolite of tryptophan.

References

1. Altman K, Greengard O. Correlation of kynurenine excretion with liver tryptophan pyrrolase levels in disease and after hydrocortisone induction. J Clin Invest. 1966 Oct;45(10):1527-1534.

2. Ashcroft GW, Crawford TB, Eccleston D, Sharman DF, MacDougall EJ, Stanton JB, Binns JK. 5-hydroxyindole compounds in the cerebrospinal fluid of patients with psychiatric or neurological diseases. Lancet. 1966 Nov 12;2(7472):1049-1052.

3. Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder. Olsson SK, Samuelsson M, Saetre P, Lindström L, Jönsson EG, Nordin C, Engberg G, Erhardt S, Landén M. J Psychiatry Neurosci. 2010 May;35(3):195-9.

4. Bearden CE, Hoffman KM, Cannon TD. The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disord. 2001;3:106-50. discussion 151-3.

5. Lichtenstein P, Yip BH, Bjork C, et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet. 2009;373:234-9.

6. Berk M, Dodd S, Kauer-Sant'anna M, et al. Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder. Acta Psychiatr Scand Suppl. 2007;434:41-9.

7. Erhardt S, Blennow K, Nordin C, et al. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett. 2001;313:96-8.

8. Nilsson LK, Linderholm KR, Engberg G, et al. Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia. Schizophr Res. 2005;80:315-22.

9. Schwarcz R, Rassoulpour A, Wu HQ, et al. Increased cortical kynurenate content in schizophrenia. Biol Psychiatry. 2001;50:521-30.

10. Atlas A, Gisslén M, Nordin C, et al. Acute psychotic symptoms in HIV-1 infected patients are associated with increased levels of kynurenic acid in cerebrospinal fluid. Brain Behav Immun. 2007;21:86-91.

11. Miller CL, Llenos IC, Dulay JR, et al. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Brain Res. 2006:1073-1074. 25-37.

12. Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in Schizophrenia. Wonodi I, Schwarcz R. Schizophr Bull. 2010 Mar;36(2):211-8. Epub 2010 Feb 10.