Medical Mimics of Schizophrenia

Introduction

  Many medical conditions can mimic schizophrenia including amphetamine psychosis, methamphetamine intoxication, mescaline intoxication, hypoglycemia, acute intermittent porphyria, etc. In acute intermittent porphria there is a lack of heme leading to the lack of a key enzyme which metabolizes tryptophan. As a result of this tryptophan accumulates and poisons the brain causing mental symptoms. This is a treatable disease. The patient is given heme.

Cancer

  Certain types of cancer result in psychiatric symptoms. Included are tumors of the adrenal glands and brain tumors.  A tumor of the adrenal medulla causes excessive catecholamines resulting in psychiatric symptoms. This provides an important clue to mental diseases. The possibility of a toxic catecholamine causing schizophrenia is very real. Catecholamines can also be made in the brain. However, the brain has little adrenaline. The brain has dopamine.

PKU

  In 1934 Dr. Asbjorn Folling of Norway discovered a genetic disease which is now called PKU (short for phenylketonuria). Folling rightfully became famous for this. In this terrible disease the amino acid phenylalanine accumulates and poisons the brain causing both mental illness and mental retardation. In one variation, caused by a deficiency of biopterin, both phenylalanine and tryptophan accumulate.

  The treatment for PKU is a special diet very low in protein. Babies are given a special formula very low in phenylalanine. The diet must be followed for life. Linus Pauling was influenced by this work and used it as evidence for "orthomolecular" psychiatry.

Nutrition

  "Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms."

Shaheen E Lakhan  and Karen F Vieira

Global Neuroscience Initiative Foundation, Los Angeles, CA, USA

  This quote is from #3 in the bibliography. Unfortunately vitamin A toxicity has been reported in people taking fish oil supplements (see #8).

Drugs

  "Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. One way for psychiatrists to overcome this noncompliance is to educate themselves about alternative or complementary nutritional treatments. Although in the cases of certain nutrients, further research needs to be done to determine the best recommended doses of most nutritional supplements, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained."

Shaheen E Lakhan  and Karen F Vieira

  The above quote is also from #3 of the bibliography. The entire text is available for free on the Internet.

  "Psychiatrists treating patients with mental disorders should be aware of available nutritional therapies, appropriate doses, and possible side effects in order to provide alternative and complementary treatments for their patients. This may reduce the number of noncompliant patients suffering from mental disorders that choose not to take their prescribed medications. As with any form of treatment, nutritional therapy should be supervised and doses should be adjusted as necessary to achieve optimal results."

  This is another quote from #3. Even though this is a very good article, I am not in 100% agreement with these scientists. One of the reasons is because of a medical mimic called hyperargininemia.

Hyperargininemia

  This terrible disease is an inborn error of metabolism much like PKU. Like PKU, it is treated by diet. Weber studied PKU and found that the excessive phenylalanine was interfering with glucose metabolism, slowing it down. Glucose metabolism is vital to the brain, which uses it to make ATP. A study has shown that something similar is happening in hyperargininemia.

  Brazilian scientists (see #12) gave arginine to rats and found, "Results showed that arginine administration significantly increased lactate release and diminished CO(2) production, glucose uptake...." Diminished glucose uptake has been repeatedly reported in schizophrenia, as has increased lactate. Probably any glucogenic amino acid would do this.

  My theory is that schizophrenia is a disorder of amino acid metabolism.

Conclusions

  Medical mimics of schizophrenia provide important clues to the etiology of the disease. I have put the pieces of the puzzle together. My theory is that certain amino acids are flooding the brain in schizophrenia. This explains the increased lactate findings, the diminished glucose uptake findings, and the neuropathology findings.

  The treatment would be a diet very low in amino acids. This would be similar to the PKU diet except that different amino acids might be involved. More research is needed. The possibility of a nutritional treatment is very real.

Bibliography

1. Pauling, L.: Orthomolecular psychiatry. Science 160: 265-271, 1968.

2. Hawkins, D., Pauling, L (eds): Orthomolecular Psychiatry; Treatment of Schizophrenia. San Francisco, W.H. Freeman and Co., 1973.

3. http://www.nutritionj.com/content/7/1/2.

4. Waring WS: Management of lithium toxicity.

Toxicol Rev 2006, 25(4):221-230.

5. Wurtman R, O'Rourke D, Wurtman JJ: Nutrient imbalances in depressive disorders. Possible brain mechanisms.

Ann N Y Acad Sci 1989, 575:75-82.

6. Eby GA, Eby KL: Rapid recovery from major depression using magnesium treatment.

Med Hypotheses 2006, 67(2):362-370.

7. Adams PB, Lawson S, Sanigorski A, Sinclair AJ: Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.

Lipids 1996, 31(Suppl):S157-S161.

8. Grubb BP: Hypervitaminosis A following long-term use of high-dose fish oil supplements.

Chest 1990, 97(5):1260.

9. Richardson AJ, Easton T, Puri BK: Red cell and plasma fatty acid changes accompanying symptom remission in a patient with schizophrenia treated with eicosapentaenoic acid.

Eur Neuropsychopharmacol 2000, 10(3):189-193.

10. Lieb J: Linoleic acid in the treatment of lithium toxicity and familial tremor.

Prostaglandins Med 1980, 4:275-279.

11. Fekkes D, Pepplinkhuizen L, Verheij R, Bruinvels J: Abnormal plasma levels of serine, methionine and taurine in transient, acute, polymorphic psychosis.

Psychiatry Res 1994, 51:11-18.

12. Brain Res. 2003 Sep 5;983(1-2):58-63. Reduction of energy metabolism in rat hippocampus by arginine administration. Delwing D, Tagliari B, Streck EL, Wannamacher CM, Wajner M, Wyse AT.

Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, RS, Porto Alegre, Brazil.