Depression Research Including Treatments

Ref. 1 favors the use of cognitive therapy. Ref. 2 implicates the kynurenine pathway of tryptophan metabolism. Ref. 3 implicates tryptophan in alcoholism.

Tryptophan Metabolism in Depression

Refs. 4, 5, and 6 discuss tryptophan metabolism in depression as well as other issues. Ref. 7 is unusual because it is available free full text at Pubmed Central.

MDMA

Ref. 9 is about MDMA, a very potent drug of abuse. This drug somewhat resembles dopamine in its chemical structure except that it has methyl groups not possessed by dopamine. There is a possibility that a methylated metabolite of dopamine could be an endogenous psychotogen.

The Prefrontal Cortex

Ref. 10 has implicated the prefrontal cortex in mood disorders, which includes depression.

Treatments

A wide variety of treatments have been proposed for depression with mixed results. Ref. 11 proposes a diet.

"Coeliac disease in adolescents has been associated with an increased prevalence of depressive and disruptive behavioural disorders, particularly in the phase before diet treatment." Ref. 11

Refs. 12-16 provide more information on celiac disease.

Orthomolecular Medicine

Linus Pauling created a stir with a brilliant 1968 paper in the journal Science called "Orthomolecular Psychiatry".

"Phenylketonuria involves the presence in the body of phenylalanine and its reaction products in amounts greater than normal. It is treated by reducing the intake of phenylalanine and in this way reducing the concentration of this substance and its reaction products to approximately the normal level. Diabetes involves a deficiency of insulin. It is treated by injecting insulin and increasing the concentration to approximately the normal value.

These diseases are controlled by changing the concentrations of substances that are normally present in the body." Pauling (1974)

The above quote is from a followup paper. Like Darwin, Pauling was immediately greeted by criticism and had to defend his theories.

"I have reached the conclusion, through arguments summarized in the following paragraphs, that a general method of treatment of disease, which may be called orthomolecular medicine, may be found to be of great value, and may turn out often to be the best method of treatment for many patients." (Pauling 1968)

"The adjective orthomolecular is used to express the idea of the right molecules in the right concentration." Pauling (1974)

"I believe that mental disease is for the most part caused by abnormal molecular concentrations of essential substances." Pauling (1974)

The rough draft of the 1974 paper is available free full text at Profiles in Science, which is at the National Library of Medicine (US) website.

Conclusions

Information about schizophrenia, which is similar to depression, is given in Refs. 17-19. More information about orthomolecular medicine is given at www.orthomolecular.org, which is an outstanding, but controversial, website. I favor the use of orthomolecular treatments for both depression and schizophrenia.

References

1. http://www.webmd.com/depression/news/20050404/talk-therapy-is-sometimes-best-for-depression

2. The kynurenine pathway in adolescent depression: Preliminary findings from a proton MR spectroscopy study. Gabbay V, Liebes L, Katz Y, Liu S, Mendoza S, Babb JS, Klein RG, Gonen O. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Sep 21. [Epub ahead of print].

3. Impact of Tryptophan Metabolism on the Vulnerability to Alcohol-Related Blackouts and Violent Impulsive Behaviours. Vignau J, Soichot M, Imbenotte M, Jacquemont MC, Danel T, Vandamme M, Lhermitte M, Allorge D. Alcohol Alcohol. 2009 Sep 16. [Epub ahead of print].

4. Indoleamine 2,3-dioxygenase activation and depressive symptoms in patients with coronary artery disease. Swardfager W, Herrmann N, Dowlati Y, Oh PI, Kiss A, Walker SE, Lanctôt KL. Psychoneuroendocrinology. 2009 Jun 18. [Epub ahead of print].

5. Neuropsychiatric disorders related to interferon and interleukins treatment. Myint AM, Schwarz MJ, Steinbusch HW, Leonard BE. Metab Brain Dis. 2009 Mar;24(1):55-68. Epub 2008 Dec 10. Review.

6. Inflammation, glutamate, and glia in depression: a literature review. McNally L, Bhagwagar Z, Hannestad J. CNS Spectr. 2008 Jun;13(6):501-10. Review.

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

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

9. Curran HV, Travill RA. Mood and cognitive effects of ±3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"): weekend "high" followed by mid-week low. Addiction. 1997;92:821-831.

10. Drevets WC, Price JL, Simpson JR, Jr, Todd RD, Reich T, Vannier M, Raichle ME. Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997;386:824-827.

11. Gluten-free diet may alleviate depressive and behavioural symptoms in adolescents with coeliac disease: a prospective follow-up case-series study. Päivi A Pynnönen, Erkki T Isometsä, Matti A Verkasalo, Seppo A Kähkönen, Ilkka Sipilä, Erkki Savilahti, and Veikko A AalbergBMC Psychiatry. 2005; 5: 14. Published online 2005 March 17. doi: 10.1186/1471-244X-5-14.

12. Ciacci C, Iavarone A, Mazzacca G, De Rosa A. Depressive Symptoms in Adult Coeliac Disease. Scand J Gastroenterol. 1998;33:247-250. doi: 10.1080/00365529850170801.

13. Addolorato G, Capristo E, Ghittoni G, Valeri C, Masciana' R, Ancona C, Gasbarrini G. Anxiety But Not Depression Decreases in Coeliac Patients After One-Year Gluten-free Diet: A Longitudinal Study. Scand J Gastroenterol. 2001;36:502-506.

14. Pynnönen P, Isometsä E, Aronen E, Verkasalo M, Savilahti E, Aalberg V. Mental disorders in adolescents with celiac disease. Psychosomatics. 2004;45:325-335. doi: 10.1176/appi.psy.45.4.325.

15. Corvaglia L, Catamo R, Pepe G, Lazzarri R, Corvaglia E. Depression in Adult Untreated Celiac Subjects: Diagnosis by the Pediatrician. Am J Gastroenterol. 1999;94:839-843.

16. Hallert C, Åström J, Walan A. Reversal of Psychopathology in Adult Coeliac Disease with the Aid of Pyridoxine (Vitamin B6). Scand J Gastroenterol. 1983;18:299-304.

17. http://www.associatedcontent.com/article/2233855/schizophrenia_as_a_toxic_encephalopathy.html

18. www.associatedcontent.com/article/2215925/the_glutamateglutamine_theory_for_schizophrenia.html

19. www.associatedcontent.com/article/2205997/excessive_amino_acids_in_the_brain.html