Estrogen - A Potential New Treatment For Women & Men With Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$227,545.00
Summary
Estrogen - the major female hormone, has been shown in animal studies to decrease the two main brain chemicals (dopamine and serotonin) that are implicated in causing schizophrenia. The effect of estrogen in the brain is similar to current antipsychotic drugs. We have carried out a study that showed that when we gave 12 young women with schizophrenia 100 micrograms of estrogen in a skin patch form plus standard antipsychotic drug treament they recovered more quickly than 12 young women who recei ....Estrogen - the major female hormone, has been shown in animal studies to decrease the two main brain chemicals (dopamine and serotonin) that are implicated in causing schizophrenia. The effect of estrogen in the brain is similar to current antipsychotic drugs. We have carried out a study that showed that when we gave 12 young women with schizophrenia 100 micrograms of estrogen in a skin patch form plus standard antipsychotic drug treament they recovered more quickly than 12 young women who received standard antipsychotic drug treatment only. 100mcg is a safe dose of estrogen. In this proposal we want to expand and clarify the pilot study resutls by conducting a 28 day trial in a total of 60 women with schizophrenia. 30 women would receive 100 mcg skin patch estrogen plus antipsychotic medication and 30 women would receive antipsychotic medicationly only. We also tested the value of adding a very small dose of oral estrogen to antipsychotic drug treatment in five men with schizophrenia and found that they made a better recovery compared to five men who received standard antipsychotic drugs only. We trialled the use of estrogen for seven days in men, but this may not have been long enough to examine the real impact of estrogen treatment in men. In this proposal we want to conduct a 14 day trial in a total of 60 men with schizophrenia. 30 men would receive 2mg of oral estrogen plus antipsychotic drug treatment and their results would be compared with 30 men who received standard antipsychotic drug treatment plus a placebo tablet identical in appearance to estrogen. For 14 days, this low dose of estrogen is very safe. Potentially estrogen may be a useful addition to the current standard treatment of schizophrenia. It may decrease the duration of acute illness and in women it may have a role in preventing relapses of schizophrenia as well as improving the general health of women with schizophrenia.Read moreRead less
Brain And Skin Blood Flow: New Animal Model For Understanding Psychiatric Disorders And Evaluating Psychotropic Agents
Funder
National Health and Medical Research Council
Funding Amount
$874,840.00
Summary
We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major brain pathway by which the constrict-the-skin-bloo ....We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major brain pathway by which the constrict-the-skin-blood-vessels message reaches the spinal cord. The pathway involves the amygdala, a forebrain region important in emotional expression and the raphe nuclei in the medulla oblongata. Drugs which affect psychological function also effect skin blood flow. Ecstasy, the street drug used to induce euphoria also constricts the skin vessels, and, sadly, the body temperature may increase so much that death ensues. Ecstasy vigorously constricts the skin blood vessels in rabbits, and temperature increases. Ecstasy is thought to act on serotonin-containing nerve cells in the brain, releasing serotonin (5-HT) onto special 5-HT2A receptors. Activation of these receptors affects both psychological function and skin blood flow. Modern drugs used to treat schizophrenia, so called atypical antipsychotics like clozapine and olanzapine, are thought to act as antagonists at 5-HT2A receptors in the brain. We were thus very excited when we discovered in our rabbit model that clozapine reverses the skin vasoconstriction induced by ecstasy. This means that we have specific hypotheses concerning the actual brain pathways and neurotransmitters whereby ecstasy and clozapine exert their effects on skin blood flow. Elucidating these pathways in rabbits and rats will provide solid knowledge concerning the mechanism of action of the atypical antipsychotics, and it may well prove possible to use our animal model to predict whether proposed new antipsychotic agents will be therapeutically effective.Read moreRead less