Anxiety: Causes and Treatment

I was nervous about writing on this topic because I didn't know what my database searches would come up with. I was afraid that I would get too many hits to study them all. However, this has happened to me before. Sure enough, I got thousands of hits, even on Pubmed Central, which restricts the hits to free full text.

When I run into this problem, I try to narrow it down by adding another word such as "tryptophan" or "lactate" or "glucose". This can narrow it down too much, but this is what I do. When I tried "tryptophan", that narrowed it down to only 26 in Pubmed Central. This is how I discovered Ref. 1.

Tryptophan and Anxiety

Ref. 1 discusses this topic. Although this represents work on mice, the article is Open Access, meaning that it can be quoted at will provided the citation is given. I have long suspected tryptophan of being involved in anxiety because excessive tryptophan in the brain is seen in acute intermittent porphyria, a metabolic disease with anxiety and other psychiatric symptoms.

"Although nutrients, including amino acids and their metabolites such as serotonin (5-HT), are strong modulators of anxiety-related behavior, the metabolic pathway(s) responsible for this physiological modulation is not fully understood."

Masaaki Kanai,1 Hiroshi Funakoshi,1 Hisaaki Takahashi,1,2 Tomoko Hayakawa,1,3 Shinya Mizuno,1 Kunio Matsumoto,1,4 and Toshikazu Nakamura1,5

1. Division of Molecular Regenerative Medicine, Department of Biochemistry and Molecular Biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan

2. Department of Molecular and Cellular Biology, School of Medicine, Ehime University, Ehime, Japan

3. Department of Vascular Regeneration, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

4. Division of Tumor Dynamics and Regulation, Kanazawa University Cancer Research Institute, Kanazawa, Japan

5. Kringle Pharma Joint Research Division for Regenerative Drug Discovery, Osaka University, Osaka 565-0871, Japan

The quote is from Ref. 1.

"These findings demonstrate a direct molecular link between Trp metabolism and neurogenesis and anxiety-related behavior under physiological conditions." (1)

Refs. 2 and 3 provide more information on this subject. However, Ref. 1 is best because it is free full text at Pubmed Central.

Obesity

Ref. 4 links obesity to mental disorders. However, weight gain is a known side effect of atypical "antipsychotics.

Psychopathology

Ref. 5 links tryptophan to psychopathology. There are known physical diseases which have symptoms of psychopathology. One example is AIP (acute intermittent porphyria, an error of tryptophan metabolism in which tryptophan floods the brain due to the lack of an enzyme). Ref. 6 is a study of acute tryptophan depletion in humans. Ref. 7 explains one pathway of tryptophan degredation. Another pathway leads to the manufacture of serotonin, an important neurotransmitter.

"Antidepressants"

Ref. 8 is a bit paradoxical. If depression is anything like AIP, then there would be too much tryptophan in the brain in depression. However, Ref. 8 reports that when rats were given "antidepressants", this caused an increase in brain tryptophan. If my theory for depression is correct, then these antidepressants would make depression worse!

Alcoholism

Ref. 9 reports abnormal tryptophan metabolism in alcoholism. Also some experiments were done giving alcohol to rats.

Other Amino Acids

There are strong reasons to believe that other amino acids may also be involved in anxiety. In celiac disease, also called sprue, excess glutamine causes anxiety. In PKU excess phenylalanine causes anxiety as well as other problems. The drug L-DOPA, which is similar to the amino acid tyrosine, causes anxiety as a side effect. It may be that any amino acid which can be burned by the brain as fuel can cause anxiety if in excess. There are theories that lactate causes anxiety. Thus the whole situation in quite complex.

Conclusions

More research needs to be done. I may study autism and ADHD and Alzheimer's disease for more clues. Almost any psychiatric disease presents with anxiety as one of the symptoms. One of these is drug abuse (10). I am proposing the vegan diet to treat anxiety because it is relatively low in amino acids (11, 12). Ref. 13 gives more information on brain disorders.

References

1. Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice.Masaaki Kanai, Hiroshi Funakoshi, Hisaaki Takahashi, Tomoko Hayakawa, Shinya Mizuno, Kunio Matsumoto, and Toshikazu Nakamura. Mol Brain. 2009; 2: 8. Published online 2009 March 27. doi: 10.1186/1756-6606-2-8.

2. Mollica RF, Cardozo BL, Osofsky HJ, Raphael B, Ager A, Salama P. Mental health in complex emergencies. Lancet. 2004;364:2058-2067. doi: 10.1016/S0140-6736(04)17519-3.

3. Peters JC. Tryptophan nutrition and metabolism: an overview. Adv Exp Med Biol. 1991;294:345-358.

4. Scott KM, McGee MA, Wells JE, Oakley Browne MA. Obesity and mental disorders in the adult general population. J Psychosom Res. 2008;64:97-105. doi: 10.1016/j.jpsychores.2007.09.006.

5. Russo S, Kema IP, Fokkema MR, Boon JC, Willemse PH, de Vries EG, den Boer JA, Korf J. Tryptophan as a link between psychopathology and somatic states. Psychosom Med. 2003;65:665-671. doi: 10.1097/01.PSY.0000078188.74020.CC.

6. Riedel WJ, Klaassen T, Schmitt JA. Tryptophan, mood, and cognitive function. Brain Behav Immun. 2002;16:581-589. doi: 10.1016/S0889-1591(02)00013-2.

7. Hayaishi O, Rothberg S, Mehler AH, Saito Y. Studies on oxygenases; enzymatic formation of kynurenine from tryptophan. J Biol Chem. 1957;229:889-896.

8. Badawy AA, Evans M. Inhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by administration of antidepressants. Biochem Pharmacol. 1981;30:1211-1216. doi: 10.1016/0006-2952(81)90299-9.

9. Adv Exp Med Biol. 1977;85A:559-69. The acute effects of ethanol on liver and brain tryptophan metabolism. Badawy AA, Evans M.

10. http://www.associatedcontent.com/article/261514/drug_abuse.html

11. www.associatedcontent.com/article/2359246/animal_rights_activism.html

12. www.associatedcontent.com/article/2339808/the_vegetarian_and_vegan_diets_to_fight.html

13. www.associatedcontent.com/article/2313589/neuroimaging_in_basic_brain_disorder.html