David Baxter PhD
Late Founder
Abortion drug may rapidly treat depression, prevent neuron loss
Tuesday, 11 July 2006
Research into a new hormone-based treatment for psychotic depression is showing promise and appears to work more quickly than existing anti-depressants. Dutch scientists, speaking at the Forum of European Neuroscience in Vienna today (Sunday 9 July) have found clues into how this works.
Dr Paul Lucassen from the University of Amsterdam has been studying the drug Mifepristone, better known by it code name RU486 which appears to reverse some of the adverse neuron and functional changes that occur in the brain during stress and depression.
Stress can lead to depression in people who have a genetic tendency to develop depression. In previous research, one of the brain regions, the hippocampus, central to memory and learning, was found to be particularly sensitive to stress. At times of chronic stress, cells in the hippocampus shrink and may even die causing memory loss. At the same time, the hippocampus continues to generate new neurons (brain cells) in adult animals as well as humans in a process known as adult neurogenesis. There are, therefore, two processes occurring in parallel: brain cell death and new cell birth in the hippocampus.
Research in rats by Dr Lucassen and others has shown that stress reduces neurogenesis. Whereas 24 hours after sudden - or acute -stress, new brain cell growth rapidly returns to normal, recovery from the effects of long-term - or chronic - but unpredictable stress may take weeks. It is not known why these processes change during stress and depression. It could be that the brain needs to adapt to the new environment and that brain cells literally have to die to make space for new brain cells in order to overcome stressful situations.
"Initially, we expected a lot of damage to the 'hard-wiring' of the brain after chronic stress, but that was not so," said Dr Lucassen. It rather appears that the turnover rate of new and old cells in the hippocampus is altered. The fact that there is no permanent damage and that stress-induced changes to the brain structure can become normal again holds considerable promise to finding a new approach to treating stress and depression.
Dr Lucassen's team has been studying how stress affects cell birth and growth, cell death, the number and volume of brain cells that produce changes in the rat hippocampus. The newly identified hormone-based treatment, RU486 blocks the effects of stress on the brain. Various clinical studies by others in large numbers of patients suffering from psychotic major depression have shown that RU486 ameliorates psychosis and depressive symptoms within a few days. "It seems to work well and quickly. We are encouraged that the patients have less depressive symptoms," said Dr Lucassen.
In order to understand the effects of stress on neurogenesis and knowing that many other anti-depressant drugs modulate neurogenesis in animal models, the team needed to find out whether a short treatment with RU486, similar to that given in the clinical studies, would also affect neurogenesis in stressed or corticosterone treated rats. They found that treatment with RU486 for four days normalised cell survival as well as neurogenesis but only in conditions of high stress. "The rapid action of RU486 is in contrast to most other anti-depressants that usually have a time lag of several weeks to months before they become effective," he said.
The new findings are consistent with the current idea that brain cell growth is required for the beneficial effects of anti- depressants to occur. The next stage of the research will first examine the underlying molecular mechanisms in more detail.
Lucassen PJ, Heine VM, De Kloet ER, Czeh B, Fuchs E, Joels M. Structural hippocampal plasticity in relation to stress and antidepressant action. FENS Forum Abstracts, vol. 3, 2006; A032.2 ? [Abstract]
Tuesday, 11 July 2006
Research into a new hormone-based treatment for psychotic depression is showing promise and appears to work more quickly than existing anti-depressants. Dutch scientists, speaking at the Forum of European Neuroscience in Vienna today (Sunday 9 July) have found clues into how this works.
Dr Paul Lucassen from the University of Amsterdam has been studying the drug Mifepristone, better known by it code name RU486 which appears to reverse some of the adverse neuron and functional changes that occur in the brain during stress and depression.
Stress can lead to depression in people who have a genetic tendency to develop depression. In previous research, one of the brain regions, the hippocampus, central to memory and learning, was found to be particularly sensitive to stress. At times of chronic stress, cells in the hippocampus shrink and may even die causing memory loss. At the same time, the hippocampus continues to generate new neurons (brain cells) in adult animals as well as humans in a process known as adult neurogenesis. There are, therefore, two processes occurring in parallel: brain cell death and new cell birth in the hippocampus.
Research in rats by Dr Lucassen and others has shown that stress reduces neurogenesis. Whereas 24 hours after sudden - or acute -stress, new brain cell growth rapidly returns to normal, recovery from the effects of long-term - or chronic - but unpredictable stress may take weeks. It is not known why these processes change during stress and depression. It could be that the brain needs to adapt to the new environment and that brain cells literally have to die to make space for new brain cells in order to overcome stressful situations.
"Initially, we expected a lot of damage to the 'hard-wiring' of the brain after chronic stress, but that was not so," said Dr Lucassen. It rather appears that the turnover rate of new and old cells in the hippocampus is altered. The fact that there is no permanent damage and that stress-induced changes to the brain structure can become normal again holds considerable promise to finding a new approach to treating stress and depression.
Dr Lucassen's team has been studying how stress affects cell birth and growth, cell death, the number and volume of brain cells that produce changes in the rat hippocampus. The newly identified hormone-based treatment, RU486 blocks the effects of stress on the brain. Various clinical studies by others in large numbers of patients suffering from psychotic major depression have shown that RU486 ameliorates psychosis and depressive symptoms within a few days. "It seems to work well and quickly. We are encouraged that the patients have less depressive symptoms," said Dr Lucassen.
In order to understand the effects of stress on neurogenesis and knowing that many other anti-depressant drugs modulate neurogenesis in animal models, the team needed to find out whether a short treatment with RU486, similar to that given in the clinical studies, would also affect neurogenesis in stressed or corticosterone treated rats. They found that treatment with RU486 for four days normalised cell survival as well as neurogenesis but only in conditions of high stress. "The rapid action of RU486 is in contrast to most other anti-depressants that usually have a time lag of several weeks to months before they become effective," he said.
The new findings are consistent with the current idea that brain cell growth is required for the beneficial effects of anti- depressants to occur. The next stage of the research will first examine the underlying molecular mechanisms in more detail.
Lucassen PJ, Heine VM, De Kloet ER, Czeh B, Fuchs E, Joels M. Structural hippocampal plasticity in relation to stress and antidepressant action. FENS Forum Abstracts, vol. 3, 2006; A032.2 ? [Abstract]
