Neuroimaging in Basic Brain Disorder Research

"Schizophrenia is a chronic and disabling brain disease characterized by psychotic episodes with unknown etiology. It is suggested that neuroinflammation plays a role in the pathophysiology of schizophrenia."

Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC.

Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

This quote is from Ref. 1. In neuroinflammation the microglia are activated.

British Work

"Subcortical structures of the brain have been studied extensively to establish their implication in the development of psychotic symptoms in schizophrenia. Any pathology in these structures of the brain identified on neuroimaging techniques can give us helpful information in learning the neuropsychiatric background of psychotic symptoms in schizophrenia." Faisal Farid and Prem MahadunMoorside Unit, Trafford General Hospital, Greater Manchester West Mental Health NHS Trust, Moorside Road, Urmston, Manchester, UK

This quote is from Ref. 2, which found an abnormality in the basal ganglia in a patient thought to be schizophrenic. The beauty of neuroimaging is that it enables scientists to locate these things in the living patient. Previously these discoveries were only made postmortem. It is a bit too late to help the patient if it is discovered postmortem. Ref. 3 reports a similar case. This data suggests that schizophrenia may be a basal ganglia disease. Ref. 4 also supports this theory.

Magnetic Resonance Spectroscopy

This technique is an adavance over the MRI. The MRI can see structural changes in the living brain. MRS can see metabolic changes. Ref. 5, which is available free full text at Pubmed Central, is a good source on MRS. Ref. 6 is also useful, but it is not on Pubmed Central. The same is true of Ref. 7.

This technique has been used to study schizophrenia, autism, and many other disorders including panic disorder.

Autism

Refs. 8, 9, and 10 discuss autism. The findings in Ref. 10 have also been reported in schizophrenia (1).

Schizophrenia

Refs. 11, 12, and 13 report low brain energy metabolism in schizophrenia. The cell membranes are also abnormal. The MRS technique has also been used to study depression and bipolar disorder.

Panic Disorder

Ref. 14 discusses panic disorder, which is thought to be associated with high brain lactate.

Bipolar Disorder

Ref. 15 reports positive findings in bipolar disorder.

"Gray matter lactate and Glx elevations in medication-free BD patients suggest a shift in energy redox state from oxidative phosphorylation toward glycolysis. The possibility of mitochondrial alterations underlying these findings is discussed and may provide a theoretical framework for future targeted treatment interventions."

Dager SR, Friedman SD, Parow A, Demopulos C, Stoll AL, Lyoo IK, Dunner DL, Renshaw PF.

Department of Radiology, University of Washington, Seattle 98105, USA. srd@u.washington.edu

The above quote is from Ref. 15. Note that energy metabolism is haywire in both schizophrenia and bipolar disorder. Thus these two diseases may be points on a continuum. All forms of mental illness could be caused by slow energy metabolism in the brain. This is consistent with PET studies (positron emission tomography). PET studies have shown slow frontal brain glucose metabolism in schizophrenia, bipolar disorder, and depression. My theory is that this may also be true in Alzheimer's disease and other forms of mental disease.

Conclusions

Ref. 16 gives information about stress, which has not been discussed in the current article. It seems that stress causes tryptophan to flood the brain cells.

There is an interesting website that explains the various diagnoses in psychiatry. This website, housed in Texas, is called HealthyPlace. The title is a bit deceptive because this site is about mental health. The URL is http://www.healthyplace.com.

Further information about brain imaging is given in Ref. 17. Information on panic disorder is given in Ref. 18. Information on treatments, including both orthomolecular treatments and drugs, is given at www.orthomolecular.org. They have an electronic newsletter, which is very interesting and very controversial. Much of their work is consistent with my own work. You can subscribe to their e-mail newsletter for free just by going to their website and giving them your e-mail address.

References

1. Neuroinflammation in Schizophrenia-Related Psychosis: A PET Study. Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC. J Nucl Med. 2009 Oct 16. [Epub ahead of print].

2. J Med Case Reports. 2009 Jul 14;3:7337. Schizophrenia-like psychosis following left putamen infarct: a case report. Farid F, Mahadun P.

3. Yurinosuke K, Jin N, Chisato O, Choi H, Kenji F, Kei Y. Schizophrenia-like psychosis following right putamen infarct. Neuropsychiatry Clin Neurosci. 2006;18:561-562.

4. Nagara T, Ohara H, Yano K, et al. Disappearance of hallucinations and delusions following left putaminal hemorrhage in a case of schizophrenia. Seishin Shinkeigaku Zasshi. 1996;98:498. [in Japanese].

5. Research Applications of Magnetic Resonance Spectroscopy (MRS) to Investigate Psychiatric Disorders. SR Dager, NM Oskin, TL Richards, and S Posse. Top Magn Reson Imaging. 2008 April; 19(2): 81-96.

6. Dager SR, Steen RG. Applications of magnetic resonance spectroscopy to the investigation of neuropsychiatric disorders. Neuropsychopharmacology. 1992;6:249-266.

7. Lyoo IK, Renshaw PF. Magnetic resonance spectroscopy: current and future applications in psychiatric research. Biol Psychiatry. 2002;51:195-207.

8. Friedman SD, Shaw DW, Artru AA, Dawson G, Petropoulos H, Dager SR. Gray and white matter brain chemistry in young children with autism. Arch Gen Psychiatry. 2006;63:786-794.

9. DeVito TJ, Drost DJ, Neufeld RW, Rajakumar N, Pavlosky W, Williamson P, Nicolson R. Evidence for cortical dysfunction in autism: a proton magnetic resonance spectroscopic imaging study. Biol Psychiatry. 2007;61(4):465-73.

10. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57:67-81.

11. Volz HR, Riehemann S, Maurer I, Smesny S, Sommer M, Rzanny R, Holstein W, Czekalla J, Sauer H. Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a (31)P chemical shift spectroscopic-imaging study. Biol Psychiatry. 2000;47:954-961.

12. Jensen JE, Miller J, Williamson PC, Neufeld RW, Menon RS, Malla A, Manchanda R, Schaefer B, Densmore M, Drost DJ. Focal changes in brain energy and phospholipid metabolism in first-episode schizophrenia: 31P-MRS chemical shift imaging study at 4 Tesla. Br J Psychiatry. 2004;184:409-415.

13. Jensen JE, Miller J, Williamson PC, Neufeld RW, Menon RS, Malla A, Manchanda, Schaefer B, Densmore M, Drost DJ. Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31PMRS chemical shift imaging at 4 Tesla. Psychiatry Res. 2006;146:127-135.

14. Dager SR, Strauss WL, Marro KI, Richards TL, Metzger GD, Artru AA. Proton magnetic resonance spectroscopy investigation of hyperventilation in subjects with panic disorder and comparison subjects. Am J Psychiatry. 1995;152:666-672.

15. Dager SR, Friedman SD, Parow A, Demopulos C, Stoll AL, Lyoo IK, Dunner DL, Renshaw PF. Brain metabolic alterations in medication-free patients with bipolar disorder. Arch Gen Psychiatry. 2004;61:450-458.

16. www.associatedcontent.com/article/2296427/stress_of_rats_and_men.html

17. www.associatedcontent.com/article/2270615/magnetic_resonance_spectroscopy_studies.html

18. www.associatedcontent.com/article/2266685/panic_disorder_research_findings.html