Depressed Mice?

Introduction

Ref. 1 has reported a mouse model of depression. If true, this could have considerable value because mice can be given bizarre diets. It might be possible to cure a depressed mouse with a bizarre diet. This reference is particularly useful because it is available free full text at the Pubmed Central database. This database is run by the U.S. government (National Library of Medicine).

Unfortunately cancer patients treated with interferon have experienced depression as a side effect (2-4). This happens because the drug changes tryptophan metabolism, which is enhanced.

Cancer Treatment

Refs. 5 & 6 report enhancement of the kynurenine pathway of tryptophan degradation as causing depression due to cancer treatment.

Alzheimer's Disease

Ref. 9 has implicated a tryptophan metabolite in Alzheimer's disease.

Depression

Refs. 10 & 11 discuss depression, which is thought to involve the kynurenine pathway of tryptophan degradation. There is a cytokine theory of depression which is related to the tryptophan theory (12, 13). The cytokine induces increased tryptophan metabolism.

Of Mice and Men

It is not at all that clear what happened to the mice. Toxicity to a mouse could look like depression to a researcher. On the other hand, depression in human could be cause by some kind of toxicity to the brain.

Schizophrenia

Like in depression, there is a search for biomarkers in schizophrenia (16). Refs. 17-20 elaborate more on this subject, which has been driving researchers crazy for years.

Treatments

"Orthomolecular medicine uses safe, effective nutritional therapy to fight illness."

Dr. Andrew Saul (21)

Ref. 22 provides information on orthomolecular medicine. This approach was advocated by the late Linus Pauling (23).

Conclusions

It is not at all clear how accurate the mouse model of depression is. There have also been attempts at rodent models for schizophrenia. One try was to give methamphetamine to the rodent. In humans methamphetamine can cause a psychosis similar to schizophrenia.

More information on tryptophan is in Ref. 24. There is a strong glutamate theory for schizophrenia. According to this theory, there is too much glutamate in the brain. This theory appears to suggest a diet low in glutamate as a treatment. Problems with psychiatric drugs are also detailed in Ref. 24. Ref. 25 has more information on amino acids.

References

1. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. J.C. O'Connor, M.A. Lawson, C. André, M. Moreau, J. Lestage, N. Castanon, K.W. Kelley, and R. Dantzer. Mol Psychiatry. Author manuscript; available in PMC 2009 November 1.

PMCID: PMC2683474

Published in final edited form as: Mol Psychiatry. 2009 May; 14(5): 511-522. Published online 2008 January 15. doi: 10.1038/sj.mp.4002148.

2. Evans DL, Charney DS, Lewis L, Golden RN, Gorman JM, Krishnan KR, et al. Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry. 2005;58(3):175-89.

3. Capuron L, Dantzer R. Cytokines and depression: the need for a new paradigm. Brain Behav Immun. 2003;17(Suppl 1):S119-24.

4. Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D. Neopterin production, tryptophan degradation, and mental depression--what is the link? Brain Behav Immun. 2002;16(5):590-5.

5. Takikawa O, Tagawa Y, Iwakura Y, Yoshida R, Truscott RJ. Interferon-gamma-dependent/independent expression of indoleamine 2,3-dioxygenase. Studies with interferon-gamma-knockout mice. Adv Exp Med Biol. 1999;467:553-7.

6. 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(5):468-73.

7. Yirmiya R. Endotoxin produces a depressive-like episode in rats. Brain Res. 1996;711(1-2):163-74.

8. Wichers MC, Koek GH, Robaeys G, Verkerk R, Scharpe S, Maes M. IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. Mol Psychiatry. 2005;10(6):538-44.

9. Guillemin GJ, Williams KR, Smith DG, Smythe GA, Croitoru-Lamoury J, Brew BJ. Quinolinic acid in the pathogenesis of Alzheimer's disease. Adv Exp Med Biol. 2003;527:167-76.

10. Lapin IP. Kynurenines as probable participants of depression. Pharmakopsychiatr Neuropsychopharmakol. 1973;6(6):273-9.

11. Mangoni A. The "kynurenine shunt" and depression. Adv Biochem Psychopharmacol. 1974;11(0):293-8.

12. Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. Andrew H. Miller, Vladimir Maletic, and Charles L. RaisonBiol Psychiatry. Author manuscript; available in PMC 2009 June 1. PMCID: PMC2680424

Published in final edited form as: Biol Psychiatry. 2009 May 1; 65(9): 732-741. Published online 2009 January 15. doi: 10.1016/j.biopsych.2008.11.029.

13. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: Inflammation and the pathogenesis of major depression. Trend Immunol. 2006;27:24-31.

14. Mossner R, Mikova O, Koutsilieri E, Saoud M, Ehlis AC, Muller N, et al. Consensus paper of the WFSBP Task Force on Biological Markers: Biological markers in depression. World J Biol Psychiatry. 2007;8:141-174.

15. Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry. 2001;58:445-452.

16. Schizophrenia genomics and proteomics: are we any closer to biomarker discovery? Shaheen E Lakhan and Alon Kramer. Behav Brain Funct. 2009; 5: 2. Published online 2009 January 7.

17. Riley B, Kendler KS. Molecular genetic studies of schizophrenia. Eur J Hum Genet. 2006;14:669-80.

18. Lakhan SE. Schizophrenia proteomics: biomarkers on the path to laboratory medicine? Diagn Pathol. 2006;1:11.

19. Coelho FM, Reis HJ, Nicolato R, Romano-Silva MA, Teixeira MM, Bauer ME, Teixeira AL. Increased serum levels of inflammatory markers in chronic institutionalized patients with schizophrenia. Neuroimmunomodulation. 2008;15:140-4.

20. Dietrich-Muszalska A, Olas B. The changes of aggregability of blood platelets in schizophrenia. World J Biol Psychiatry. :1-6. 2007, Sep 14.

21. http://www.orthomolecular.org/subscribe.html

22. Klenner FR (1979) The significance of high daily intake of ascorbic acid in preventive medicine, in: Physician's Handbook on Orthomolecular Medicine, Third Edition, 1979, Roger Williams, PhD, ed., p 51-59.

23. Pauling L (1986) How to Live Longer And Feel Better, by Linus Pauling (Paperback - May 2006) ISBN-13: 9780870710964.

24. www.associatedcontent.com/article/2436896/medical_research_on_tryptophan.html

25. www.associatedcontent.com/article/2425658/amino_acid_research.html