The Biochemical Approach to Mental Illness

Unfortunately there have been bad problems with psychiatric drugs (1, 2). However, new drugs are being studied (3).

Energy Metabolism

Ref. 4 reports "energy metabolism dysregulation" in schizophrenia. This is not a new theory, but represents new data supporting an old finding.

"Our data supports a dysregulation of energy metabolism in schizophrenia as well as suggests new markers that may contribute to a better understanding of this complex disease." Daniel Martins-de-Souza et al (2009)

The quote is from Ref. 4. This is an open-access article, so it can be quoted as long as the citation is given.

"Most proteins we identified as differentially expressed (52%) are enzymes involved the regulation of energy metabolism. Their altered levels can lead to an overall disturbance, and ultimately contribute to the establishment of pathological states." Martins-de-Souza et al (Ref. 4)

Genetic Theories

Genetic theories abound in schizophrenia (5-7).

Proteomics

This approach looks for abnormal proteins and for alterations in normal proteins. Refs. 4, 10, 11, and 12 use this approach, which appears to be very promising.

Neuropathology

Ballooned cells have been reported by many investigators. Fungfeld (1952) reported lipid degeneration in the thalamus and other areas in schizophrenia (14). Hopf (1952) reported similar findings in the pallidum in 9 of 10 catatonic patients (15). Bruetsch (1952) reported rheumatoid nodules and endothelial proliferation. He also found demyelination (16).

Van der Horst (1952)

Van der Horst reported perivascular hemorrhage, cell infiltration, fibrillary gliosis, and cell degeneration (17).

Hyden (1952)

Hyden reported decreased levels of nucleoproteins in a cortical biopsy (18). This may be an important clue because RNA is used to make proteins from amino acids.

Tatetsu (1974)

This Japanese neuropathologist reported thick hyperargyrophilic apical dendrites and axons in the cortex (19).

Miyakawa et al (1972)

These Japanese scientists used the electron microscope also (20). They found granular deposits in the cytoplasm of oligodendrocytes in the cortex. They also found abnormal synaptic membranes.

Stevens (1982)

Stevens found corpora amylacea, which are starch bodies seen in errors of glucose metabolism (13). They mean that glucose is being metabolized too slowly in the brain. She also found gliosis.

Heath (1954)

Using depth electrodes, Heath localized schizophrenia to the septal area of the brain (21). In this area he found abnormal EEG readings.

Conclusions

It appears that schizophrenia, and perhaps all forms of mental disease, is characterized by a slowing of brain glucose metabolism. Thus it is a kind of diabetes of the brain. But what is the treatment? Since diabetes can be treated by diet, can schizophrenia be treated by diet?

Orthomolecular treatments are discussed in Refs. 22-24. These are nutritional treatments.

References

1. Catatonia as a risk factor for the development of neuroleptic malignant syndrome: report of a case following treatment with clozapine.

Paparrigopoulos T, Tzavellas E, Ferentinos P, Mourikis I, Liappas J.

World J Biol Psychiatry. 2009;10(1):70-3.

2. Aripiprazole treatment of risperidone-induced hyperprolactinemia.

Chen JX, Su YA, Wang SL, Bian QT, Liu YH, Wang N, De Yang F, Haile C, Kosten TR, Zhang XY.

J Clin Psychiatry. 2009 Jul;70(7):1058-9.

3. Apud JA, Weinberger DR. Treatment of cognitive deficits associated with schizophrenia: potential role of catechol-O-methyltransferase inhibitors. CNS Drugs. 2007;21:535-557.

4. Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation

Daniel Martins-de-Souza, Wagner F Gattaz, Andrea Schmitt, José C Novello, Sérgio Marangoni, Christoph W Turck, and Emmanuel Dias-NetoBMC Psychiatry. 2009; 9: 17. Published online 2009 April 30. doi: 10.1186/1471-244X-9-17.

5. Mirnics K, Middleton FA, Marquez A, Lewis DA, Levitt P. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron. 2000;28:53-67.

6. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, Haroutunian V, Fienberg AA. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci USA. 2001;98:4746-51.

7. Middleton FA, Mirnics K, Pierri JN, Lewis DA, Levitt P. Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia. J Neurosci. 2002;22:2718-29.

8. Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB, Starkey M, Webster MJ, Yolken RH, Bahn S. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet. 2003;362:798-805.

9. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, Wayland M, Freeman T, Dudbridge F, Lilley KS, Karp NA, Hester S, Tkachev D, Mimmack ML, Yolken RH, Webster MJ, Torrey EF, Bahn S. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 2004;9:684-97. 643.

10. Clark D, Dedova I, Cordwell S, Matsumoto I. A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia. Mol Psychiatry. 2006;11:459-70. 423.

11. Novikova SI, He F, Cutrufello NJ, Lidow MS. Identification of protein biomarkers for schizophrenia and bipolar disorder in the postmortem prefrontal cortex using SELDI-TOF-MS ProteinChip profiling combined with MALDI-TOF-PSD-MS analysis. Neurobiol Dis. 2006;23:61-76.

12. Sivagnanasundaram S, Crossett B, Dedova I, Cordwell S, Matsumoto I. Abnormal pathways in the genu of the corpus callosum in schizophrenia pathogenesis: a proteome study. Proteomics clin appl. 2007;1:1291-1305.

13. Stevens JR. Neuropathology of schizophrenia. Arch Gen Psychiatry 1982; 39: 1131-9.

14. Fungfeld EW:: Pathologisch-anatomische Untersuchungen im Nucleus anterior thalami bei Schizophrenie, in Proceedings of the International Congress of Neuropathology. Turin, Italy, Rosenberg & Sellier, 1952, vol 3, pp 648-659.

15. Hopf A: Über histopathologische Veränderungen im Pallidum und Striatum bei Schizophrenie, in Proceedings of the International Congress of Neuropathology. Turin, Italy, Rosenberg & Sellier, 1952, vol 3, pp 629-635.

16. Bruetsch WL: Specific structural neuropathology of the central nervous system (rheumatic, demyelinating, vasofunctional, etc) in schizophrenia, in Proceedings of the First International Congress of Neuropathology. Turin, Italy, Rosenberg & Sellier, 1952, vol 1, pp 487-499.

17. Van der Horst L: Histopathology of clinically diagnosed schizophrenic psychoses or schizophrenia-like psychoses of unknown origin, in Proceedings of the International Congress of Neuropathology. Turin, Italy, Rosenberg & Sellier, 1952, vol 3, pp 648-659.

18. Hyden H: Nerve cell chemistry and neuropathological problems studied by means of quantitative methods, in Proceedings of the First International Congress of Neuropathology. Turin, Italy, Rosenberg & Sellier, 1952, vol 3, pp 570-594.

19. Tatetsu S: On histologie findings in schizophrenia and schizophrenic state, in Mitsuda H, Fukuda T (eds): Biological Mechanisms of Schizophrenia and Schizophrenia-like Psychoses. Tokyo, Igaku-Shoin Ltd, 1974, pp 288-289.

20. Miyakawa T, Sumiyoshi S, Deshimaru M, et al: Electron microscopic study on schizophrenia: Mechanisms of pathological changes. Acta Neuropathol 1972;20:67-77.
21. Heath RG. Studies in Schizophrenia. Cambridge, Mass: Harvard University Press; 1954.

22. www.associatedcontent.com/article/2062441/healthcare_reform_how_it_could_save.html

23. www.associatedcontent.com/article/2053991/mental_healthcare_politics_and_research.html
24. www.associatedcontent.com/article/2034097/the_latest_research_in_psychiatry.html