Medical Breakthroughs in Brain Research

There have been new reports of tests for schizophrenia. These tests are biological (1). Ref. 2 gives a test for depression. It seems that tryptophan metabolism is abnormal in depression.

Tryptophan Metabolism

"Cytokine induction of the enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in the development of major depressive disorder (MDD)." Gabbay et al (2)

Ref. 3 also reported abnormal tryptophan metabolism in depression. A decreased plasma concentration of tryptophan could reflect a flooding of the cells with tryptophan due to a transport error. Ref. 4 reports depressive symptoms as a side effect of interferon. This drug, used as a cancer treatment, increases tryptophan metabolism.

Drugs
"The weller you are the more drugs you can take without getting sick. That's why doctors don't get into more trouble than they do with therapy."Eugene Stead Jr., 1968
Believe it or not, this came from the American College of physicians website!
Mitochondria
Ref. 5 implicates "mitochondrial dysfunction" in psychiatric disorders. Ref. 6 is consistent with Ref. 5. "Postmortem, genetic, brain imaging, and peripheral cell studies all support decreased mitochondrial activity as a factor in the manifestation of Bipolar Disorder (BD)." Cataldo et al (6)
Ref. 6 was written by a Harvard group.
Metabolic Changes
Ref. 7 is from Seattle. This group reported "gray matter lactate and Glx elevations in medication-free BD patients". Here Glx means the sum of the amino acids glutamate, glutamine, and gamma-aminobutyric acid. It could be that the lactate elevations are caused by the amino acid elevations. According to Ref. 8, elevated lactate is a sign of mitochondrial compromise. This adds further support to the mitochondrial theory for bipolar disorder. But what causes the mitochondrial compromise? The answer to that question could be worthy of the Nobel prize. It would appear that amino acids flooding the cells could be causing the mitochondrial compromise. Ref. 9 further implicates the mitochondria.
Panic Disorder
Panic disorder has also been investigated by Dager and his group (10). It seems that lactate can induce panic in these individuals (10, 11). Brain lactate was found to be high.
Japanese Work
Japanese scientists have studied bipolar disorder (12, 13). Decreased brain pH could be caused by lactic acid excess. Ref. 13 reports further evidence for mitochondrail dysfunction in bipolar disorder.
Conclusions
It appears that abnormal amino acid metabolism may be causing mitochondrial dysfunction in various mental disorders including depression, bipolar disorder, panic disorder, etc. But what is the treatment? Since amino acids are found in the diet, dietary treatment is suggested. A diet low in amino acids might be helpful. Such a diet would be low in protein. This appears to support some of the food allergy theories in orthomolecular psychiatry.
References

1. Chromatin alterations in leukocytes of first-episode schizophrenic patients. Kloukina-Pantazidou I, Havaki S, Chrysanthou-Piterou M, Kontaxakis VP, Papadimitriou GN, Issidorides MR. Ultrastruct Pathol. 2010 May;34(3):106-16.

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. 2010 Feb 1;34(1):37-44. Epub 2009 Sep 21.

3. 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.

4. 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.

5. Mitochondrial dysfunction and psychiatric disorders. Jou SH, Chiu NY, Liu CS. Chang Gung Med J. 2009 Jul-Aug;32(4):370-9.

6. Abnormalities in Mitochondrial Structure in Cells from Patients with Bipolar Disorder. Cataldo AM, McPhie DL, Lange NT, Punzell S, Elmiligy S, Ye NZ, Froimowitz MP, Hassinger LC, Menesale EB, Sargent LW, Logan DJ, Carpenter AE, Cohen BM. Am J Pathol. 2010 Jun 21.

7. Arch Gen Psychiatry. 2004 May;61(5):450-8. Brain metabolic alterations in medication-free patients with bipolar disorder. Dager SR, Friedman SD, Parow A, Demopulos C, Stoll AL, Lyoo IK, Dunner DL, Renshaw PF.

8. Lin DD, Crawford TO, Barker PB. Proton MR spectroscopy in the diagnostic evaluation of suspected mitochondrial disease. AJNR Am J Neuroradiol. 2003;24:33-41.

9. Kato T, Kunugi H, Nanko S, Kato N. Mitochondrial DNA polymorphisms in bipolar disorder. J Affect Disord. 2001;62:151-164. FULL TEXT | WEB OF SCIENCE | PUBMED

10. Dager SR, Marro KI, Metzger GD, Richards TL. Preliminary applications of magnetic resonance spectroscopy to investigate lactate-induced panic. Am J Psychiatry. 1994;151:57-63. FREE FULL TEXT

11. Dager SR, Richards T, Strauss WL, Artru A. Single-voxel ¹H MRS investigation of brain metabolic changes during lactate-induced panic. Psychiatry Res. 1997;76:89-99. WEB OF SCIENCE | PUBMED

12. Kato T, Murashita J, Kamiya A, Shioiri T, Kato N, Inubushi T. Decreased brain intracellular pH measured by ³¹P-MRS in bipolar disorder: a confirmation in drug-free patients and correlation with white matter hyperintensity. Eur Arch Psychiatry Clin Neurosci. 1998;248:301-306. FULL TEXT | WEB OF SCIENCE | PUBMED

13. Kato T, Kato N. Mitochondrial dysfunction in bipolar disorder. Bipolar Disord. 2000;2:180-190. FULL TEXT | WEB OF SCIENCE | PUBMED