Posted by SLS on March 19, 2001, at 18:12:44
In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk?, posted by steve on March 16, 2001, at 3:51:38
Hi Steve.
I owe you an apology for my past reactions to your suggestion that neuroleptics produce brain damage by causing a shrinking of the brain. I am still dubious of this conclusions, as the data concerning reduction in brain mass remains equivocal. I don't think it serves well to state with certainty that brain shrinkage occurs. However, after reading the most recent threads regarding tardive dyskinesia, I feel that your characterization of its nature as being "brain damage" is justified. I hadn't realized the extent to which neurotoxic explanations for tardive dyskinesia (and perhaps schizophrenia itself) have developed.
I found the following two abstracts during a quick search on Medline for references to tardive dyskinesia and free radicals. Both studies suggest that the schizophrenia disorder itself may involve aberrant biological events that lead to the formation of abnormally high concentrations of damaging free radicals. I don't know if the experimental observations using these specific indices have been repeated. However, there may be a clinical observation that serves to cooraborate the results of the study. I recall that an abnormally high rate of idiopathic spontaneous dyskinesias occurs in schizophrenics who have not yet been exposed to medication. Investigators are searching for biological markers to determine which individuals are more succeptable to develop schizophrenia and TD. I read several studies that looked to identify alleles for specific enzyme polymorphisms that are believed to allow for increased levels of free radicals.
Sincerely,
Scott-----------------------------------------------------------------------
12: Prostaglandins Leukot Essent Fatty Acids 1996 Aug;55(1-2):33-43 Books,
LinkOut
Free radical pathology in schizophrenia: a review.Reddy RD, Yao JK
University of Pittsburgh Medical Center, Western Psychiatric Institute and
Clinic, PA 15213, USA.There is evidence that free radicals are involved in membrane pathology,
and may play a role in schizophrenia. Free radicals are reactive chemical
species generated during normal metabolic processes, and, in excess, can
damage lipids, proteins, and DNA. Regions of high oxygen consumption,
lipid content, and transition metals are at particular risk. Hence,
neuronal membranes are uniquely vulnerable to radical-mediated damage.
Elaborate antioxidant defense systems exist to protect against oxidative
stress. In schizophrenia there is evidence for dysregulation of free
radical metabolism, as detected by abnormal activities of critical
antioxidant enzymes and other indices of lipid peroxidation in plasma, red
blood cells, and cerebrospinal fluid. Such abnormalities have been
associated with tardive dyskinesia, negative symptoms, neurological signs,
poor premorbid function, and CT scan abnormalities. Studies to date have
generally been exploratory. Further elucidation of the role of free
radicals and antioxidants in schizophrenia and its treatment will require
systematic investigation.Publication Types:
Review
Review, tutorialPMID: 8888121
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: Neuropsychopharmacology 2000 Aug;23(2):170-7 Books, LinkOut
Manganese superoxide dismutase gene polymorphism and schizophrenia:
relation to tardive dyskinesia.Hori H, Ohmori O, Shinkai T, Kojima H, Okano C, Suzuki T, Nakamura J
Department of Psychiatry, School of Medicine, University of Occupational
and Environmental Health, Kitakyushu, Japan.There has been increasing evidence that deranged superoxide dismutase
(SOD) activities might be a risk factor for schizophrenia and/or tardive
dyskinesia (TD). In the present study, we investigated the genetic
association between a functional polymorphism (Ala-9Val) in the human
manganese (Mn) SOD gene and schizophrenia or TD (192 schizophrenics: 39
with TD and 153 without TD; 141 controls). No significant differences in
the allelic or genotypic distribution between schizophrenics and controls
were observed. However, we did find a significant difference in genotypic
distribution between schizophrenics with and those without TD (p =. 03).
Moreover, decreased -9Ala (mutant) allele was found among patients with TD
(p =.02; odds ratio = 0.29; 95% confidence interval = 0.10-0.83). In
conjunction with previous findings of increased free radicals and
decreased SOD activities in TD subjects, these results suggest that the
-9Ala (high activity) MnSOD allele may play a role in protecting against
susceptibility to TD in schizophrenics.PMID: 10882843
poster:SLS
thread:56412
URL: http://www.dr-bob.org/babble/20010319/msgs/56938.html