November 09, 2007

Blood Pressure Drug May be a "Vaccine" for Mental Illness and Minimize Brain Damage

A new study suggests that an existing drug used to treat high blood pressure and enlargement of the prostate may protect the brain from damage that is related to schizophrenia and other psychiatric disorders linked to high levels of stress hormones in the brain.

This is a potentially important study that could have significant applications in early treatment programs for psychosis and schizophrenia. If, as some researchers are suggesting, mental illness is in part a result of damage to the brain from high levels of stress hormones, a drug that blocks these stress hormones might act as a "vaccine-like" medication, or as a brain damage prevention agent, against the stress-triggers for mental illness.

Additionally, CBT therapy and psycho-education could be provided at the same time as the medication so as to help the person learn how to lower their own stresses and therefore eliminate the need for the medications in the longer term. These approaches might also be valuable in minimizing risk of relapse-associated brain damage for people who already have schizophrenia. Additional studies need to be done to find out if this might be the case. This is still only very preliminary research - we'll report on this in greater details when follow-on studies come out.

The blood pressure medication called Prazosin, also prescribed as an antipsychotic medication, appears to block the increase of steroid hormones known as glucocorticoids researchers have found. Elevated levels of glucocorticoids are associated with atrophy in nerve branches where impulses are transmitted, and even nerve cell death, in the hippocampus. (For more information see our recent story on how stress-related Glucocorticoids damage the brain and raise risk of mental illness).

The hippocampus is the elongated ridge located just under the cerebral cortex of the brain where emotions and memory are processed.

"It's known, from human studies, that corticosteroids are not good for you cognitively," said study co-author S. Paul Berger, M.D., assistant professor of psychiatry and behavioral neuroscience, OHSU School of Medicine and the PVAMC. "We think prazosin protects the brain from being damaged by excessive levels of corticosteroid stress hormones."

The study, titled "Prazosin attenuates dexamethasone-induced HSP70 expression in the cortex," is being presented during a poster session today at Neuroscience 2007, the annual Society for Neuroscience conference in San Diego.

Scientists believe stress activates a neurochemical response in the brain that triggers the release of glucocorticoids in the brain, and that high levels of glucocorticoids in blood serum are associated with such psychiatric conditions as schizophrenia, depression, PTSD and Alzheimer's disease. This mechanism has been linked to decreases in cognitive performance in older people who are not suffering from clinical dementia.

"Our hypothesis is that just being afraid of being blown up all the time means you have high levels of steroids all the time," Berger said, referring to PTSD among military personnel.

Low levels of glucocorticoids have anti-inflammatory effects in the brain, but high levels can trigger inflammatory mechanisms that damage nerve cells by activating an enzyme that causes oxidative stress. Even a single exposure to a high dose of glucocorticoids can be sufficient to damage nerve cells: A previous study showed synthetic glucocorticoid therapy to treat autoimmune disorders such as rheumatoid arthritis can induce mood disorders, including psychosis, and cognitive impairment known as "steroid dementia" in severe forms.

To determine the effects of prazosin, OHSU and PVAMC researchers, led by Altaf Darvesh, Ph.D., formerly of the OHSU Department of Psychiatry, administered a glucocorticoid called dexamethasone to rats, then measured the expression of a protein known as heat shock protein 70, or HSP70, that serves as a marker for neurotoxicity. Pretreatment with prazosin, an alpha-1 receptor antagonist, resulted in "significant" slowing of dexamethasone-induced expression in the cerebral cortex.

"The one thing we don't know for sure is, would you have to get it before you're traumatized," Berger said. "Lots of people have high levels of corticosteroids when they're under stress, so could we give them prazosin ahead of time to protect them from brain damage?"

Berger said future research will continue to look at where and how steroids cause brain damage, and just when prazosin would have to be administered to most effectively protect the brain against damage.

"We just looked at brain damage," he said. "Steroids are known to cause cognitive impairment in both rats and people, so the next step is to see if we can correlate brain damage with cognitive effects and determine if we can protect against brain damage to protect cognition."

The study was funded by the U.S. Department of Veterans Affairs.

Source: Press release from Oregon Health & Science University.

Related Reading: Lower Level of Stress for Child while growing up May Significantly Lower Schizophrenia Risk


Wow, scary, scary. More drugs, a vaccine? Maybe we can find the base plant or mineral and just eat the stuff straight out of nature.

Posted by: warmfirelight at November 9, 2007 05:31 PM

Wow, I was diagnosed almost 3 years ago and my blood pressure has always been a bit on the low side. Does anyone know what would happen if I took a high blood pressure medication? Would my pressure drop to dangerously even deadly levels?

Posted by: warmfirelight at November 9, 2007 05:46 PM

Prolactin can be involved in prostate enlargement, if this medicine is blocking prolactin there could be a problem as dopamine and prolactin operate in antagonism, excess dopamine causes psychosis.
Also if you had mental problems but no stress you would have no motivation to change and might accept faulty thinking patterns.

Posted by: Josh at November 11, 2007 01:31 PM

About as much a vaccine as paracetamole is for the flu.

This idea has lightly been buzzing round since the first alpha blockers were invented.

these companies use there old drug stock way to much to squeeze as many matabolites out as they can and don't really know what they are doing.
In order to get a true picture as to how usful small and large chemicals can be for areas of medical science relating to schizophrenia we need more chemicals to be simulated, analised and produced to choose from.

Also taking this will still have side effects like sadation and lack of sex drive and therefore is in no way a direct sutible vaccine no doubt they'll try and push it as one though.

P's don't delete this(again) i'm not paranoid about some bleaching group but they obviously are about me.

Posted by: Luke Andrew at November 14, 2007 05:10 PM


This study was done by academic researchers that work for Oregon University and the Government (the Veterans Administration) - NOT a drug company.

Unless you have information that shows the researchers were getting money from the Pharma company that owns the drug - you're drawing conclusions that are not supported by the evidence.

Given that the study was not funded by any pharma company - and in fact was funded by university and government working to help people - I think that a more accurate statement is that the research is likely focused on helping prevent mental illness - and it seems that the research suggests it may succeed in this. Opinions without evidence aren't worth much - we encourage you to look try to balance the evidence before you make conclusions.

Posted by: SzAdministrator at November 15, 2007 12:59 PM

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