The older theory of depression was that it resulted from a deficiency of neurotransmitters like serotonin, dopamine or epinephrine. The monkey wrench in the spokes of this theory was that taking an anti-depressant immediately increased the supply of the deficient neurotransmitter in brain synapses but it took several weeks to notice an improvement in mood. If depression was caused solely by an under supply of a neurotransmitter like serotonin, and Prozac increases the brain’s stock of serotonin right away, then why wouldn’t a depressed patient taking Prozac feel better right away?
About a decade ago neuroscientists established that new brain cells are born in adults in an area of the brain called the hippocampus. This birthing process was called neurogenesis (neuro for neurons and genesis for birth of). They also discovered that depressed patients have much lower rates of neurogenesis than normals in their hippocampus and that their hippocampi are smaller, on average about 20% smaller than that of normals. Is reduced neurogenesis the cause of depression, a result of depression, or both?
Depression is initially a response to chronic stress, but depression stresses the brain because being in a state of chronic fight-flight keeps cortisol levels high and cortisol kills brain cells in the hippocampus. Neurophysiologists like Robert Sapolsky, Ph.D. showed that one reason for the difference in hippocampal size between depressed and non-depressed individuals is that high cortisol levels shrinks their hippocampi.
Over the past decade a number of neuroscientists have shown that antidepressants stimulate neurogenesis in the adult human hippocampus, which means they increase the rate of production of new neurons there. Based on this observation, some neuroscientists have hypothesized that antidepressants improve depression by stimulating neurogenesis there. The theory goes that antidepressants take a few weeks to work because time is needed to birth enough new brain cells to alter mood. Some have questioned the theory on the grounds that the hippocampus facilitates memory and learning, but has little to do with mood regulation.
The theory is being tested on mice to see if anti-depressants had an immediate or a delayed effect in reversing depressed behavior. A mouse is considered to be depressed if he falls quickly off of a stick instead of holding on with his tail or quickly resorts to floating in a beaker of water instead of trying to vigorously swim his way out. If antidepressants work on such a mouse, he will hold onto the stick upside down with his tail for a much longer time and will swim in the beaker of water for a much longer time.
Mice, like humans, have a protein called CREB (cAMP response element-binding protein) which binds to DNA sequences, affects gene expression and affects the rate of neurogenesis. Scientists created a strain of CREB deficient mice which tend to be anxious. They observed that the CREB deficient mice had a higher rate of neurogenesis in their hippocampi than normal mice but had the same amount of serotonin as normal mice. When CREB deficient mice were given the tail suspension test and forced swim test they did well showing they were not depressed. Then the researchers depleted the amount of serotonin in their brains. This not only caused the CREB deficient mice to flunk the tail suspension and forced swim tests (showing them to be depressed), but they showed reduced neurogenesis in their hippocampi. Giving the CREB deficient mice an antidepressant enabled them to perform normally on the two tests right away without delay.
In second test the scientists gave normal mice and CREB deficient mice Reeses pieces. Both gobbled them up right away in a familiar environment, but when placed in a new environment (which induced stress) they took time to feel comfortable in the new environment before they would eat their beloved Reeses pieces. When the normal mice were given antidepressants they immediately ate the Reeses pieces in the new environment but the CREB deficient mice needed a few weeks.
This research was published in 2007 by Tamar L.Gur and colleagues in the Departments of Pharmacology and Psychiatry at the University of Pennsylvania School of Medicine in the Journal. Their article is titled cAMP Response Element-Binding Protein Deficiency Allows for Increased Neurogenesis and a Rapid Onset of Antidepressant Response.
This publication and others like it leave the field in a state of confusion. We do know that antidepressant medication increases neurogenesis in the hippocampus, but we still can’t explain why extra new brain cells there would improve mood, why there is a delay in beneficial effects or all antidepressant users and why less than half of depressed people respond well to antidepressants. The research will continue, but for now the idea that neurogenesis explains why antidepressants work in humans is just an intriguing possibility. Some researchers have predicted it will one day explain why some people benefit but will not become a universal explanation.
The older theory of depression was that it resulted from a deficiency of neurotransmitters like serotonin, dopamine or epinephrine. The monkey wrench in the spokes of this theory was that taking an anti-depressant immediately increased the supply of the deficient neurotransmitter in brain synapses but it took several weeks to notice an improvement in mood. If depression was caused solely by an under supply of a neurotransmitter like serotonin, and Prozac increases the brain’s stock of serotonin right away, then why wouldn’t a depressed patient taking Prozac feel better right away?
About a decade ago neuroscientists established that new brain cells are born in adults in an area of the brain called the hippocampus. This birthing process was called neurogenesis (neuro for neurons and genesis for birth of). They also discovered that depressed patients have much lower rates of neurogenesis than normals in their hippocampus and that their hippocampi are smaller, on average about 20% smaller than that of normals. Is reduced neurogenesis the cause of depression, a result of depression, or both?
Depression is initially a response to chronic stress, but depression stresses the brain because being in a state of chronic fight-flight keeps cortisol levels high and cortisol kills brain cells in the hippocampus. Neurophysiologists like Robert Sapolsky, Ph.D. showed that one reason for the difference in hippocampal size between depressed and non-depressed individuals is that high cortisol levels shrinks their hippocampi.
Over the past decade a number of neuroscientists have shown that antidepressants stimulate neurogenesis in the adult human hippocampus, which means they increase the rate of production of new neurons there. Based on this observation, some neuroscientists have hypothesized that antidepressants improve depression by stimulating neurogenesis there. The theory goes that antidepressants take a few weeks to work because time is needed to birth enough new brain cells to alter mood. Some have questioned the theory on the grounds that the hippocampus facilitates memory and learning, but has little to do with mood regulation.
The theory is being tested on mice to see if anti-depressants had an immediate or a delayed effect in reversing depressed behavior. A mouse is considered to be depressed if he falls quickly off of a stick instead of holding on with his tail or quickly resorts to floating in a beaker of water instead of trying to vigorously swim his way out. If antidepressants work on such a mouse, he will hold onto the stick upside down with his tail for a much longer time and will swim in the beaker of water for a much longer time.
Mice, like humans, have a protein called CREB (cAMP response element-binding protein) which binds to DNA sequences, affects gene expression and affects the rate of neurogenesis. Scientists created a strain of CREB deficient mice which tend to be anxious. They observed that the CREB deficient mice had a higher rate of neurogenesis in their hippocampi than normal mice but had the same amount of serotonin as normal mice. When CREB deficient mice were given the tail suspension test and forced swim test they did well showing they were not depressed. Then the researchers depleted the amount of serotonin in their brains. This not only caused the CREB deficient mice to flunk the tail suspension and forced swim tests (showing them to be depressed), but they showed reduced neurogenesis in their hippocampi. Giving the CREB deficient mice an antidepressant enabled them to perform normally on the two tests right away without delay.
In second test the scientists gave normal mice and CREB deficient mice Reeses pieces. Both gobbled them up right away in a familiar environment, but when placed in a new environment (which induced stress) they took time to feel comfortable in the new environment before they would eat their beloved Reeses pieces. When the normal mice were given antidepressants they immediately ate the Reeses pieces in the new environment but the CREB deficient mice needed a few weeks.
This research was published in 2007 by Tamar L.Gur and colleagues in the Departments of Pharmacology and Psychiatry at the University of Pennsylvania School of Medicine in the Journal. Their article is titled cAMP Response Element-Binding Protein Deficiency Allows for Increased Neurogenesis and a Rapid Onset of Antidepressant Response.
This publication and others like it leave the field in a state of confusion. We do know that antidepressant medication increases neurogenesis in the hippocampus, but we still can’t explain why extra new brain cells there would improve mood, why there is a delay in beneficial effects or all antidepressant users and why less than half of depressed people respond well to antidepressants. The research will continue, but for now the idea that neurogenesis explains why antidepressants work in humans is just an intriguing possibility. Some researchers have predicted it will one day explain why some people benefit but will not become a universal explanation.
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SAMe stands for S-adenosyl methionine. It is a naturally occurring molecule first discovered in Italy in 1952 by G.L. Cantoni. Most of it is produced and consumed in the human liver. It is involved in over 40 metabolic reactions including biosynthesis of certain nucleic acids and proteins. A company called Pharmavite makes and sells SAMe as a dietary (non-drug) supplement for depression help.
On the level of neurotransmitters, the human motivation to undertake action comes largely from the transmission (signaling) of dopamine. In July 2010 neuroscientist Mitchell F. Roitman, Ph.D., an Assistant Professor of Psychology at the University of Illinois in Chicago, announced the results of his research into the effect of a high fat diet on dopamine signaling in the brains of rats. He plans to publish his research in a prestigious journal within the next month or so.
It has often been said that major depression is a condition of extremes, leaving the depressed person thinking only in terms of worst case scenarios, blaming himself for whatever goes wrong in his life, refusing to allow himself to experience pleasure and refusing to give himself credit for any positive accomplishment. Non-depressed people moderate their vision of themselves and the world around them. They see the world as good and the bad. They can experience pleasure as well as pain. They sometimes blame themselves and sometimes blame others. They alternate between hope and fear. In a figurative sense depressed people are unable to see shades of gray while non-depressed people can.
Epidemiologists know that women experience anxiety disorders three times as much as men and depression twice as much as men. In the past psychologists tried to account for this based on socialization. They noted that women are more open to talking about their feelings than men, and thus more likely to be diagnosed with a mood disorder than men. Before the women’s liberation movement, women were largely denied the right to work and were kept at home as housewives and mothers without the opportunity to engage their talents and leadership abilities. For many women this was an understandable source of frustration, grief, anger and depression. The expression “mother’s little helper” coined by the Rolling Stones in a song in 1966 referred to abuse of prescription drugs to get bored moms through their day.