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Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » SLS

Posted by steve on March 20, 2001, at 1:02:04

In reply to Re: ADVICE PLEASE-Want to try Geodon, but TD risk? » steve, posted by SLS on March 19, 2001, at 18:12:44

Thank you, thank you.

Isn't it sad that doctors don't tell you this, and that pharma companies aren't forced to label their "APDs" as neurotoxic?

If you want something to really chew on, you might like searching medline for free radicals, schizophrenia and melatonin. All studies of Melatonin in paranoid schizophrenics report that melatonin levels, are greatly below normal. Melatonin, as you may know, is one of the best chemicals to mop up free radicals. And at one time I believed that psychiatry is about solving "chemical imbalances." Now I believe it is about causing them and toxicities, as long as money can be made. And damn the patients.

S.

> 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, tutorial
>
> PMID: 8888121
>
> -----------------------------------------------------------------------
>
>
> : 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


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