Brilliant Discoveries in Psychiatric Research

There are many different forms of mental illness. All are diseases of the brain. All may involve reduced brain glucose metabolism. Many may involve abnormal tryptophan metabolism.

Depression

"Glucocorticoids, such as cortisol, are vital hormones that are released in response to stress, and regulate metabolism and immunity but also neuronal survival and neurogenesis. Interestingly depression is highly prevalent in infectious, autoimmune and neurodegenerative diseases and at the same time, depressed patients show higher levels of pro-inflammatory cytokines."

Zunszain PA, Anacker C, Cattaneo A, Carvalho LA, Pariante CM.

Stress, Psychiatry and Immunology Laboratory (SPI-Lab), Centre for the Cellular Basis of Behaviour, Department of Psychological Medicine, Institute of Psychiatry, King's College London, 125 Coldharbour Lane, SE5 9NU, London, United Kingdom.

The above quote is from Ref. 1. There are many theories for depression. A lot of these involve tryptophan. Ref. 2 implicates abnormal tryptophan metabolism. Ref. 2 is by Gabbay V, Klein RG, Katz Y, Mendoza S, Guttman LE, Alonso CM, Babb JS, Hirsch GS, and Liebes L. of the NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, NY, USA.

MDD is short for major depressive disorder.

Schizophrenia

Similar reports have appeared about schizophrenia (3). Ref. 3 is by Wonodi I, and Schwarcz R. of the
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 21228, USA. Iwonodi@mprc.umaryland.edu.

Tryptophan

The finding of decreased plasma concentration of tryptophan in major depression (4) may indicate that tryptophan is flooding the cells. This may mean that major depression and schizophrenia are related. A flooding of the brain with tryptophan in schizophrenia would explain the increased tryptophan metabolites found in the brain in schizophrenia.

Neuropathology

Ref. 5 reports positive neuropathology findings in the basal ganglia, which are high in dopamine. If this is true, then things are complex. An error in dopamine metabolism might be causing the tryptophan to flood the brain cells in schizophrenia and depression.

Interferon

Interferon is a drug used to treat cancer. Unfortunately this drug causes depression as a side effect. It seems that interferon alters tryptophan metabolism (6, 7).

Conclusions

With all of this smoke there is probably a fire. It appears that tryptophan is involved adversely in various forms of mental disorders. Ref. 8 provides further evidence for increased tryptophan metabolism in the pyrrolase pathway. Ref. 9 reports cellular alterations in depression.

But why is all of this important? First of all, it does not support the drug companies' theory of serotonin being low. If anything, the serotonin should be high with tryptophan flooding the brain cells. Second, it supports an orthomolecular treatment. This treatment would be a diet low in tryptophan. Since sugar and fat both enhance tryptophan transport into the brain, it also suggest a diet low in sugar and low in fat. Sugar is frowned upon by orthomolecular scientists including the late Linus pauling and the late Abram Hoffer. Also niacin should be given as a supplement to avoid pellagra.

References

1. Glucocorticoids, cytokines and brain abnormalities in depression. Zunszain PA, Anacker C, Cattaneo A, Carvalho LA, Pariante CM. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Apr 18.

2. The possible role of the kynurenine pathway in adolescent depression with melancholic features. Gabbay V, Klein RG, Katz Y, Mendoza S, Guttman LE, Alonso CM, Babb JS, Hirsch GS, Liebes L. J Child Psychol Psychiatry. 2010 Apr 12.

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

4. 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.

5. Baumann B, Danos P, Krell D, Diekmann S, Leschinger A, Stauch R, et al. Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a postmortem study. J Neuropsychiatry Clin Neurosci. 1999;11:71-8.

6. 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.

7. Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry. 2002;7:468-73.

8. Curzon G, Bridges PK. Tryptophan metabolism in depression. J Neurol Neurosurg Psychiatry. 1970;33:698-704.

9. Hercher C, Turecki G, Mechawar N. Through the looking glass: Examining neuroanatomical evidence for cellular alterations in major depression. J Psychiatr Res. 2009;43:947-61.