Biomarkers in Mental Diseases
"It is also suggested that kynurenines participate in the pathophysiology of psychiatric disorders. Thus, elevated levels of KYNA have been found in the CSF as well as in the post-mortem brain of patients with schizophrenia." Erhardt et al (Ref. 4)
The above Swedish group reviewed studies on tryptophan metabolites in schizophrenia. These metabolites were high. This suggests a hypercatabolism of tryptophan in schizophrenia, at least in the kynurenine pathway. Similar results were reported in Ref. 1.
Swedish Work
This work is from the famous Karolinska Institute in Stockholm which awards the Nobel prizes in medicine.
"Kynurenic acid (KYNA) is an endogenous compound implicated in the pathophysiology of schizophrenia." Olsson et al (6)
I found these references using the Pubmed database provided by the US National Library of Medicine. This group found KYNA to be pharmacologicaly active.
Similar work was reported from Ireland (5).
"These results provide evidence for kynurenine pathway upregulation, specifically involving the first enzymatic step, in patients with major psychotic disorder." Barry et al (2008) (Ref. 5)
An American group, Miller et al, also published similar findings (1).
"Increased concentrations of kynurenine pathway metabolites have been reported by several groups for disorders involving psychosis, including schizophrenia and bipolar disorder." Miller et al
Dutch Work
"The upregulation of the initiating step of the kynurenine pathway was demonstrated in postmortem anterior cingulated cortex from individuals with schizophrenia and bipolar disorder." Myint et al (Holland) (Ref. 8)
Glutamate Theory
There is also a glutamate theory for schizophrenia (9). However, even Ref. 9 supports the tryptophan theory.
"Accordingly, an increase of TDO activity has been observed in critical CNS regions of schizophrenics. These mechanisms result in an accumulation of KYNA in critical CNS regions."
Muller N, Schwarz M. (9)
The enzyme TDO metabolizes tryptophan into the kynurenine pathway.
Conclusions
Ref. 10 reports that kynurenic acid has pharmacological activity. This reference is available free full text at the journal website. The first 9 references have only free abstracts.
Most of this data confirms my own theory of amino acids, particularly tryptophan, flooding the brain cells (16-20). To me this suggests a diet very low in amino acids, particularly tryptophan. This would be a low protein diet. Many of the references from Pubmed suggest a new drug. Maybe if there was a drug that would make people eat less protein, then such a drug might help. However, it would be simpler and cheaper just for the patient to eat less protein.
References
1. Miller CL, Llenos IC, Cwik M, Walkup J, Weis S. Alterations in kynurenine precursor and product levels in schizophrenia and bipolar disorder. Neurochem Int. 2008;52:1297-303.
2. Lutkenhoff ES, van Erp TG, Thomas MA, Therman S, Manninen M, Huttunen MO, Kaprio J, Lönnqvist J, O'Neill J, Cannon TD. Proton MRS in twin pairs discordant for schizophrenia. Mol Psychiatry.
3. Huang JT, Leweke FM, Tsang TM, Koethe D, Kranaster L, Gerth CW, Gross S, Schreiber D, Ruhrmann S, Schultze-Lutter F, Klosterkötter J, Holmes E, Bahn S. CSF metabolic and proteomic profiles in patients prodromal for psychosis. PLoS ONE. 2007;2:e756.
4.
Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders.
Erhardt S, Olsson SK, Engberg G.
CNS Drugs. 2009;23(2):91-101. doi: 10.2165/00023210-200923020-00001. Review.
PMID: 19173370 [PubMed - indexed for MEDLINE]
5.
Kynurenine pathway in psychosis: evidence of increased tryptophan degradation.
Barry S, Clarke G, Scully P, Dinan T.
J Psychopharmacol. 2009 May;23(3):287-94. Epub 2008 Jun 18.
PMID: 18562404 [PubMed - in process]
6. Elevated levels of kynurenic acid change the dopaminergic response to amphetamine: implications for schizophrenia.
Olsson SK, Andersson AS, Linderholm KR, Holtze M, Nilsson-Todd LK, Schwieler L, Olsson E, Larsson K, Engberg G, Erhardt S.
Int J Neuropsychopharmacol. 2009 May;12(4):501-12. Epub 2008 Sep 17.
PMID: 18796185 [PubMed - in process]
7. Brain Res. 2006 Feb 16;1073-1074:25-37. Epub 2006 Jan 30. Links
Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder.Miller CL, Llenos IC, Dulay JR, Weis S.
8. Tryptophan breakdown pathway in bipolar mania.
Myint AM, Kim YK, Verkerk R, Park SH, Scharpé S, Steinbusch HW, Leonard BE.
J Affect Disord. 2007 Sep;102(1-3):65-72. Epub 2007 Jan 30.
PMID: 17270276 [PubMed - indexed for MEDLINE]
9. Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission.
Muller N, Schwarz M.
Neurotox Res. 2006 Oct;10(2):131-48. Review.
PMID: 17062375 [PubMed - indexed for MEDLINE]
10. Elevations of endogenous kynurenic acid produce spatial working memory deficits.
Chess AC, Simoni MK, Alling TE, Bucci DJ.
Schizophr Bull. 2007 May;33(3):797-804. Epub 2006 Aug 18.
PMID: 16920787 [PubMed - indexed for MEDLINE]
11. Schwarcz R, Pellicciari R. Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. J Pharmacol Exp Ther. 2002;303:1-10.
12. Stone TW. Neuropharmacology of quinolinic and kynurenic acids. Pharmacol Rev. 1993;45:309-379.
13. Sawa A, Snyder SH. Schizophrenia: neural mechanisms for novel therapies. Mol Med. 2003;9:3-9.
14. Schwarcz R, Rassoulpour A, Wu H-Q, Medoff D, Tamminga CA, Roberts RC. Increased cortical kynurenate content in schizophrenia. Biol Psychiatry. 2001;50:521-530.
15. Erhardt S, Blennow K, Nordin C, Skogh E, Lindstrom LH, Engberg G. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett. 2001;313:96-98.
16. www.associatedcontent.com/article/1698919/advances_in_biological_psychiatric.html
17. www.associatedcontent.com/article/1680090/cuban_research_on_schizophrenia.html
18. www.associatedcontent.com/article/1680380/the_virus_theory_for_schizophrenia.html
19. www.associatedcontent.com/article/1676885/new_ideas_in_psychiatry.html
20. www.associatedcontent.com/article/1649109/mitochondrial_dysfunction_in_mental.html
Published by Craig Olson
I have worked at many different jobs including as a scientist, a mental health worker, a physical health worker, etc. I am an advocate for better health care and an advocate for the disabled. View profile
Schizophrenia Versus Bipolar Disorder - What's the Difference?What are the differences between bipolar disorder and schizophrenia? How can people get help for mental health, hallucinations, manic behavior, depression and psychotic disorders?- The Scientific Study of Schizophrenia and a SolutionSchizophrenia is caused by a toxin which makes amino acids flood the cells. A strict diet is recommended.
- Review of Charles G. Martignette et al: The Great American Pin UpIf you are a pin-up art fan, this is a must have book. Well worth the $5 (hardback).
- Major Depression and Other Mental DisordersMajor depression appears to be caused by excessive metabolism of tryptophan. A low tryptophan diet is suggested.
- Excessive Catabolism of Tryptophan in Mental DiseasesThere is massive evidence that tryptophan metabolism is abnormal in the various forms of mental disease. This is also true in Huntington's chorea, which has psychiatric symptoms.
- Advances in Biochemical Psychiatry
- Mitochondrial Dysfunction in Mental Diseases
- Biochemical Aberrations in Mental Diseases
- More Mental Health Research is Needed
- Amino Acids in Psychiatry
- Child Temper Tantrum or Pediatric Bipolar Disorder?
- Bipolar Disorder and Structured Religion