Posts tagged serotonin
Articles and news from the latest research reports.
Neuroscientists use snail research to help explain “chemo brain”
It is estimated that as many as half of patients taking cancer drugs experience a decrease in mental sharpness. While there have been many theories, what causes “chemo brain” has eluded scientists.
In an effort to solve this mystery, neuroscientists at The University of Texas Health Science Center at Houston (UTHealth) conducted an experiment in an animal memory model and their results point to a possible explanation. Findings appeared in The Journal of Neuroscience.
In the study involving a sea snail that shares many of the same memory mechanisms as humans and a drug used to treat a variety of cancers, the scientists identified memory mechanisms blocked by the drug. Then, they were able to counteract or unblock the mechanisms by administering another agent.
“Our research has implications in the care of people given to cognitive deficits following drug treatment for cancer,” said John H. “Jack” Byrne, Ph.D., senior author, holder of the June and Virgil Waggoner Chair and chairman of the Department of Neurobiology and Anatomy at the UTHealth Medical School. “There is no satisfactory treatment at this time.”
While much work remains, Byrne, who runs the university’s Neuroscience Research Center, said understanding how these drugs impact the brain is an important first step in alleviating this condition characterized by forgetfulness, trouble concentrating and difficulty multitasking.
Byrne’s laboratory is known for its use of a large snail called Aplysia californica to further the understanding of the biochemical signaling among nerve cells (neurons). The snails have large neurons that relay information much like those in humans.
When Byrne’s team compared cell cultures taken from normal snails to those administered a dose of a cancer drug called doxorubicin, the investigators pinpointed a neuronal pathway that was no longer passing along information properly.
With the aid of an experimental drug, the scientists were able to reopen the pathway. Unfortunately, this drug would not be appropriate for humans, Byrne said. “We want to identify other drugs that can rescue these memory mechanisms,” he added.
The scientists confirmed their findings in tests on the nerve cells of rats.
“The big picture is to determine if this cancer drug acts in the same way in humans,” Byrne said.
Single dose of antidepressant changes the brain
A single dose of antidepressant is enough to produce dramatic changes in the functional architecture of the human brain. Brain scans taken of people before and after an acute dose of a commonly prescribed SSRI (serotonin reuptake inhibitor) reveal changes in connectivity within three hours, say researchers who report their observations in the Cell Press journal Current Biology on September 18.
"We were not expecting the SSRI to have such a prominent effect on such a short timescale or for the resulting signal to encompass the entire brain," says Julia Sacher of the Max Planck Institute for Human Cognitive and Brain Sciences.
While SSRIs are among the most widely studied and prescribed form of antidepressants worldwide, it’s still not entirely clear how they work. The drugs are believed to change brain connectivity in important ways, but those effects had generally been thought to take place over a period of weeks, not hours.
The new findings show that changes begin to take place right away. Sacher says what they are seeing in medication-free individuals who had never taken antidepressants before may be an early marker of brain reorganization.
Study participants let their minds wander for about 15 minutes in a brain scanner that measures the oxygenation of blood flow in the brain. The researchers characterized three-dimensional images of each individual’s brain by measuring the number of connections between small blocks known as voxels (comparable to the pixels in an image) and the change in those connections with a single dose of escitalopram (trade name Lexapro).
Their whole-brain network analysis shows that one dose of the SSRI reduces the level of intrinsic connectivity in most parts of the brain. However, Sacher and her colleagues observed an increase in connectivity within two brain regions, specifically the cerebellum and thalamus.
The researchers say the new findings represent an essential first step toward clinical studies in patients suffering from depression. They also plan to compare the functional connectivity signature of brains in recovery and those of patients who fail to respond after weeks of SSRI treatment.
Understanding the differences between the brains of individuals who respond to SSRIs and those who don’t “could help to better predict who will benefit from this kind of antidepressant versus some other form of therapy,” Sacher says. “The hope that we have is that ultimately our work will help to guide better treatment decisions and tailor individualized therapy for patients suffering from depression.”
New research offers help for spinal cord patients
In a study on rats, researchers at the University of Copenhagen have discovered the cause of the involuntary muscle contractions which patients with severe spinal cord injuries frequently suffer. The findings have just been published in the Journal of Neuroscience and, in the long run, can pave the way for new treatment methods.
Three thousand Danish patients suffer from severe spinal cord injuries after being involved in traffic accidents or accidents at work. An injury to the spinal cord is a catastrophe for the individual, and often results in complete or partial paralysis of the person’s arms and legs. Despite the paralysis, several patients experience problems with involuntary muscle contractions or spasms which impair the patient’s quality of life.
The movements are due to the neurotransmitter serotonin, which normally plays a crucial role in relation to our voluntary control of movements by reinforcing the level of activity in the motor neurones when they have to activate the muscles to an extraordinary degree. Research shows that a group of cells in the spinal cord start supplying serotonin in an uncontrolled way following an injury, and this knocks the motor system out of control.
“We now have a qualified idea of why the serotonin level goes out of control, and we have documented that a special serotonin-producing enzyme plays a key role. By targeting the specific enzyme, in the long term we will be able to devise new methods of treatment when we are trying to impact functions in the nervous system,” says associate professor and neurophysiologist Jacob Wienecke.
The prospects of the study are interesting for both spinal cord patients and patients suffering from Parkinson’s disease.
Emergency response kicks in
The enzyme aromatic L-amino acid decarboxylase (AADC) plays an important role in the production of the neurotransmitter serotonin:
“In the first few days after an injury to the spinal cord, we can see there is a very rapid regulation of AADC which results in the uncontrolled production of serotonin. It is our guess that this is the spinal cord’s emergency response trying to boost the enzyme’s capacity,” says Jacob Wienecke.
According to the researchers, it may be the same emergency response which causes the involuntary movements – dyskinesia – that are also experienced by patients with Parkinson’s disease. However, for Parkinson’s patients, it is the dopamine system which is affected, but the enzyme which activates the emergency response is the same.
“It is an interesting perspective, which will hopefully focus efforts on targeting drugs specifically at the AADC cells. Perhaps in the future we can regulate the undesired neural activity in this way so that the unnecessary ‘disturbance on the line’ disappears for the affected patients,” says Jacob Wienecke.
Existing treatment puts a damper on learning
Existing forms of treatment for spinal cord patients currently involve, for example, using the drug baclofen, which suppresses neural activity, and thereby the motor neurones which cause the involuntary movements. The problem with baclofen though is that it impacts motor learning – and thus the patients’ rehabilitation. However, there is still a long way to go. Developing new drugs is a protracted process, and the way is paved with obstacles. Injuries to the spinal column are extremely complex, and primarily result in interruptions to the signalling between the brain and the body.
“Finding a solution to the problem is no easy task. However, a lot suggests that regulating serotonin production more precisely could mitigate undesirable spasms while also supporting the rehabilitation of controlled movements. So far, the study has been carried out on rats, but we have reason to believe that the same mechanisms apply in humans,” says Jacob Wienecke in conclusion.
New study throws into question long-held belief about depression
New evidence puts into doubt the long-standing belief that a deficiency in serotonin — a chemical messenger in the brain — plays a central role in depression. In the journal ACS Chemical Neuroscience, scientists report that mice lacking the ability to make serotonin in their brains (and thus should have been “depressed” by conventional wisdom) did not show depression-like symptoms.
Donald Kuhn and colleagues at the John D. Dingell VA Medical Center and Wayne State University School of Medicine note that depression poses a major public health problem. More than 350 million people suffer from it, according to the World Health Organization, and it is the leading cause of disability across the globe. In the late 1980s, the now well-known antidepressant Prozac was introduced. The drug works mainly by increasing the amounts of one substance in the brain — serotonin. So scientists came to believe that boosting levels of the signaling molecule was the key to solving depression. Based on this idea, many other drugs to treat the condition entered the picture. But now researchers know that 60 to 70 percent of these patients continue to feel depressed, even while taking the drugs. Kuhn’s team set out to study what role, if any, serotonin played in the condition.
To do this, they developed “knockout” mice that lacked the ability to produce serotonin in their brains. The scientists ran a battery of behavioral tests. Interestingly, the mice were compulsive and extremely aggressive, but didn’t show signs of depression-like symptoms. Another surprising finding is that when put under stress, the knockout mice behaved in the same way most of the normal mice did. Also, a subset of the knockout mice responded therapeutically to antidepressant medications in a similar manner to the normal mice. These findings further suggest that serotonin is not a major player in the condition, and different factors must be involved. These results could dramatically alter how the search for new antidepressants moves forward in the future, the researchers conclude.
Fed Up with Waiting? Timely Activation of Serotonin Enhances Patience
Lining up in a long queue for a popular restaurant or waiting for the arrival of a date requires a great deal of patience. Our lives are full of decisions involving patience, yet it needs to be exercised at the appropriate times. In order to examine the brain mechanism for controlling patience to obtain a reward, Drs. Kayoko Miyazaki and Katsuhiko Miyazaki and Prof. Kenji Doya of the Neural Computation Unit at the Okinawa Institute of Science and Technology Graduate University, used a new technique called optogenetics, where they use light to simulate specific neurons with precise timing. Their most recent research shows that activating serotonin neurons specifically during waiting promotes patience for delayed rewards. This research was published in the online version of Current Biology on August 21, 2014.
In this study, the researchers used genetically engineered mice that produce light-activated molecules only in neurons that produce serotonin. They implanted an optical fiber in a small part of the brain called the dorsal raphe, from which neural fibers releasing serotonin extend throughout the cerebrum, the largest and most highly developed part of the brain. The researchers trained five of those mice to perform a delayed reward task, meaning that if they waited at a hole, they would receive a food pellet as a reward. To show that they were waiting, each mouse needed to hold its nose inside the hole where the food pellet would appear, a posture that the researchers call a nose poke. The durations of waiting were randomly chosen from 3, 6, or 9 seconds, or infinity, meaning no reward was given no matter how long the mice waited. In half of those trials, researchers stimulated serotonin neurons by shining a light through the optical fiber while the mice were waiting. No prior signal was given to notify how long the waiting would be. The mice consistently waited for 3 and 6 seconds to receive the food. But when the mice needed to wait for 9 seconds, the mice showed difficulty and often removed their nose from the food hole. When the researchers shone a light on serotonin neurons during the nose poke position, the light stimulation significantly decreased the number of failures to wait for 9 seconds to obtain the food.
In the 25% of trials, the food pellet reward was not delivered regardless of how long the mouse waited. In these trials, without their serotonin neurons stimulated, mice waited 12.0 seconds on average. With their serotonin neurons stimulated, the mice waited 17.5 seconds on average. As control experiments, the researchers activated serotonin neurons at different timing when each mouse did not have its nose poked into the food hole, then observed that these mice behaved the same as in unstimulated cases with no evidence of simple motor inhibition. The results showed, for the first time, that the timed activation of serotonin neurons promotes animals’ patience for delayed rewards.
Serotonin is a neuromodulator that is released diffusely in the entire brain. It is involved in behavioral, cognitive, and mental functions. Classically, serotonin was believed to signal punishment and inhibit behaviors. However, serotonin enriching drugs, known as SSRI, are effective for therapies of depression, which is hard to reconcile with the classic view. Another recent study of optogenetic stimulation of serotonin neurons even reported its effect as a reward, to further complicate the story. On the other hand, another line of research, including the previous work by the OIST researchers, showed that the lack of serotonin causes impulsive behaviors. “Our previous studies have shown that serotonin levels increase when waiting for delayed rewards. We have also shown that inhibiting serotonin neurons leads to an inability to wait for a long time,” explained Kayoko and Katsuhiko Miyazaki. “By using light to stimulate neurons at specific times, this study has proven serotonin’s role in patience during delayed reward waiting, underlining serotonin’s much greater role than previously thought.” By further exploring the effect of serotonin, the researchers hope to decipher the neuronal network behind mental disorders and behaviors involving serotonin. Such studies can promote a better understanding of human emotions, including the development of software and robots and that think and act like humans.
Discovery of new pathways controlling the serotonergic system
With the aid of new methods, a research team at Karolinska Institutet have developed a detailed map of the networks of the brain that control the neurotransmitter serotonin. The study, published in the scientific journal Neuron, may lead to new knowledge on a number of psychiatric conditions and the development of new pharmaceuticals.
The neurotransmitter serotonin controls impulsivity, mood and our cognitive functions, among other things, and comes from the serotonergic neurons – the neurons that produce serotonin. So that we have good mental health and normal behaviour, it is important that there is correctly regulated activity among these neurons. The activity is governed by other neurons from different regions of the brain via direct links, known as synapses, on the serotonergic neurons. Imbalance in the serotonergic system can lead to depression, Parkinson’s disease, schizophrenia and autism, among other things.
So far it has been impossible to study in detail how different types of nerve cells are interlinked and how the brain’s networks control behaviour. Consequently, there has also been a lack of knowledge of which nerve cells control the activity of the serotonergic neurons. But with the help of new methods, researchers at Karolinska Institutet can now investigate how the various networks of the brain are organised and how they work. The research team, led by Konstantinos Meletis of the Department of Neuroscience, has established which networks of the brain control the serotonergic neurons.
“We have been able to create a new type of map of the neurons’ contacts and discovered new pathways that control the serotonergic system. These networks were previously unknown and are very interesting in terms of how they help us to understand how the serotonergic system works, which could also help us to understand certain mental illnesses,” Konstantinos Meletis explains.
In order to map out which neurons have direct contact with serotonergic neurons, the researchers established a method in which these cells were marked with a rabies virus which produced a fluorescent marker. Via genetic manipulation, the rabies virus was then spread to all of the neurons directly linked to the serotonergic neurons. The researchers thereby gained a very detailed, three-dimensional image of the networks of the brain that control serotonin. Using optogenetics, a method in which light is used to control the activity of neurons, the researchers were then able to manipulate select networks and thus study their effect on the serotonergic neurons.
Via mapping, the researchers discovered a network in the frontal lobe which is associated with cognition and well-being and which controls the serotonergic neurons. Researchers also found that serotonin can be controlled from new types of neurons in the basal ganglia, an area of the cerebrum which among other things controls movement, well-being and decision-making; a discovery which may have significance for conditions such as Parkinson’s disease.
“We are very optimistic that the revolution we are now seeing in brain research could also lead to entirely new and effective medicine in the field of psychiatry,” Konstantinos Meletis explains.
Small DNA modifications predict brain’s threat response
The tiny addition of a chemical mark atop a gene that is well known for its involvement in clinical depression and posttraumatic stress disorder can affect the way a person’s brain responds to threats, according to a new study by Duke University researchers.
The results, which appear online August 3 in Nature Neuroscience, go beyond genetics to help explain why some individuals may be more vulnerable than others to stress and stress-related psychiatric disorders.
The study focused on the serotonin transporter, a molecule that regulates the amount of serotonin signaling between brain cells and is a major target for treatment of depression and mood disorders. In the 1990s, scientists discovered that differences in the DNA sequence of the serotonin transporter gene seemed to give some individuals exaggerated responses to stress, including the development of depression.
(Image caption: An artist’s conception shows how molecules called methyl groups attach to a specific stretch of DNA, changing expression of the serotonin transporter gene in a way that ultimately shapes individual differences in the brain’s reactivity to threat. The methyl groups in this diagram are overlaid on the amygdala of the brain, where threat perception occurs. Credit: Annchen Knodt, Duke University)
Sitting on top of the serotonin transporter’s DNA (and studding the entire genome), are chemical marks called methyl groups that help regulate where and when a gene is active, or expressed. DNA methylation is one form of epigenetic modification being studied by scientists trying to understand how the same genetic code can produce so many different cells and tissues as well as differences between individuals as closely related as twins.
In looking for methylation differences, “we decided to start with the serotonin transporter because we know a lot about it biologically, pharmacologically, behaviorally, and it’s one of the best characterized genes in neuroscience,” said senior author Ahmad Hariri, a professor of psychology and neuroscience and member of the Duke Institute for Brain Sciences.
"If we’re going to make claims about the importance of epigenetics in the human brain, we wanted to start with a gene that we have a fairly good understanding of," Hariri said.
This work is part of the ongoing Duke Neurogenetics Study (DNS), a comprehensive study linking genes, brain activity and other biological markers to risk for mental illness in young adults.
The group performed non-invasive brain imaging in the first 80 college-aged participants of the DNS, showing them pictures of angry or fearful faces and watching the responses of a deep brain region called the amygdala, which helps shape our behavioral and biological responses to threat and stress.
The team also measured the amount of methylation on serotonin transporter DNA isolated from the participants’ saliva, in collaboration with Karestan Koenen at Columbia University’s Mailman School of Public Health in New York.
The greater the methylation of an individual’s serotonin transporter gene, the greater the reactivity of the amygdala, the study found. Increased amygdala reactivity may in turn contribute to an exaggerated stress response and vulnerability to stress-related disorders.
To the group’s surprise, even small methylation variations between individuals were sufficient to create differences between individuals’ amygdala reactivity, said lead author Yuliya Nikolova, a graduate student in Hariri’s group. The amount of methylation was a better predictor of amygdala activity than DNA sequence variation, which had previously been associated with risk for depression and anxiety.
The team was excited about the discovery but also cautious, Hariri said, because there have been many findings in genetics that were never replicated.
That’s why they jumped at the chance to look for the same pattern in a different set of participants, this time in the Teen Alcohol Outcomes Study (TAOS) at the University of Texas Health Science Center at San Antonio.
Working with TAOS director, Douglas Williamson, the group again measured amygdala reactivity to angry and fearful faces as well as methylation of the serotonin transporter gene isolated from blood in 96 adolescents between 11 and 15 years old. The analyses revealed an even stronger link between methylation and amygdala reactivity.
"Now over 10 percent of the differences in amygdala function mapped onto these small differences in methylation," Hariri said. The DNS study had found just under 7 percent.
Taking the study one step further, the group also analyzed patterns of methylation in the brains of dead people in collaboration with Etienne Sibille at the University of Pittsburgh, now at the Centre for Addiction and Mental Health in Toronto.
Once again, they saw that methylation of a single spot in the serotonin transporter gene was associated with lower levels of serotonin transporter expression in the amygdala.
"That’s when we thought, ‘Alright, this is pretty awesome,’" Hariri said.
Hariri said the work reveals a compelling mechanistic link: Higher methylation is generally associated with less reading of the gene, and that’s what they saw. He said methylation dampens expression of the gene, which then affects amygdala reactivity, presumably by altering serotonin signaling.
The researchers would now like to see how methylation of this specific bit of DNA affects the brain. In particular, this region of the gene might serve as a landing place for cellular machinery that binds to the DNA and reads it, Nikolova said.
The group also plans to look at methylation patterns of other genes in the serotonin system that may contribute to the brain’s response to threatening stimuli.
The fact that serotonin transporter methylation patterns were similar in saliva, blood and brain also suggests that these patterns may be passed down through generations rather than acquired by individuals based on their own experiences.
Hariri said he hopes that other researchers looking for biomarkers of mental illness will begin to consider methylation above and beyond DNA sequence-based variation and across different tissues.
(Source: eurekalert.org)
Anxiety in invertebrates opens research avenues
For the first time, CNRS researchers and the Université de Bordeaux have produced and observed anxiety-like behavior in crayfish, which disappears when a dose of anxiolytic is injected. This work, published in Science on June 13, 2014, shows that the neuronal mechanisms related to anxiety have been preserved throughout evolution. This analysis of ancestral behavior in a simple animal model opens up new avenues for studying the neuronal bases for this emotion.
Anxiety can be defined as a behavioral response to stress, consisting in lasting apprehension of future events. It prepares individuals to detect threats and anticipate them appropriately so as to increase their chances of survival. However, when stress is chronic, anxiety becomes pathological and may lead to depression.
Until now, non-pathological anxiety had only been described in humans and a few vertebrates. For the first time, it has been observed in an invertebrate. To achieve this, researchers at the Institut de Neurosciences Cognitives et Intégratives d’Aquitaine (CNRS/Université de Bordeaux) and the Institut des Maladies Neurodégénératives (CNRS/Université de Bordeaux) repeatedly exposed crayfish to an electric field for thirty minutes. They then placed the crayfish in an aquatic cross-shaped maze. Two arms of the maze were lit up (which repels the crustaceans) and two were dark—which they find reassuring.
The researchers analyzed the exploratory behavior of the crayfish. Those made anxious tended to remain in the dark areas of the maze, by contrast to control crayfish, which explored the entire maze. This behavior is an adaptive response to a felt stress: the animal aims to minimize the risk of meeting an attacker. This emotional state wore itself out after about one hour.
Anxiety in crayfish is correlated to increased serotonin concentration in their brains. Neurotransmitter serotonin is involved in regulating many physiological processes in both invertebrates and humans. It is released when stress is experienced and regulates several responses related to anxiety, such as increasing blood glucose levels. The researchers have also highlighted that injecting an anxiolytic commonly used in humans (benzodiazepine) stops the prevention behavior in crayfish. This shows how early neural mechanisms that trigger or inhibit anxiety-like behavior appeared in the evolutionary process and that they have been well preserved over time.
This work provides researchers specializing in stress and anxiety with a unique animal model. Crayfish have a simple nervous system whose neurons are easy to record, so they may shed light on the neuronal mechanisms at work when stress is experienced, as well as on the role of neurotransmitters such as serotonin or GABA. The team now plans to study anxiety in crayfish subject to social stress and the neuronal changes that occur when the anxiety is prolonged for several days.
Tiny Molecule Could Help Diagnose and Treat Mental Disorders
Scientists “fingerprint” a culprit in depression, anxiety and other mood disorders
According to the World Health Organization, such mood disorders as depression affect some 10% of the world’s population and are associated with a heavy burden of disease. That is why numerous scientists around the world have invested a great deal of effort in understanding these diseases. Yet the molecular and cellular mechanisms that underlie these problems are still only partly understood.
The existing anti-depressants are not good enough: Some 60-70% of patients get no relief from them. For the other 30-40%, that relief is often incomplete, and they must take the drugs for a long period before feeling any effects. In addition, there are many side effects associated with the drugs. New and better drugs are clearly needed, an undertaking that requires, first and foremost, a better understanding of the processes and causes underlying the disorders.
The Weizmann Institute’s Prof. Alon Chen, together with his then PhD student Dr. Orna Issler, investigated the molecular mechanisms of the brain’s serotonin system, which, when misregulated, is involved in depression and anxiety disorders. Chen and his colleagues researched the role of microRNA molecules (small, non-coding RNA molecules that regulate various cellular activities) in the nerve cells that produce serotonin. They succeeded in identifying, for the first time, the unique “fingerprints” of a microRNA molecule that acts on the serotonin-producing nerve cells. Combining bioinformatics methods with experiments, the researchers found a connection between this particular microRNA, (miR135), and two proteins that play a key role in serotonin production and the regulation of its activities. The findings appeared today in Neuron.
The scientists noted that in the area of the brain containing the serotonin-producing nerve cells, miR135 levels increased when antidepressant compounds were introduced. Mice that were genetically engineered to produce higher-than-average amounts of the microRNA were more resistant to constant stress: They did not develop any of the behaviors associated with chronic stress, such as anxiety or depression, which would normally appear. In contrast, mice that expressed low levels of miR135 exhibited more of these behaviors; in addition, their response to antidepressants was weaker. In other words, the brain needs the proper miR135 levels – low enough to enable a healthy stress response and high enough to avoid depression or anxiety disorders and to respond to serotonin-boosting antidepressants. When this idea was tested on human blood samples, the researchers found that subjects who suffered from depression had unusually low miR135 levels in their blood. On closer inspection, the scientists discovered that the three genes involved in producing miR135 are located in areas of the genome that are known to be associated with risk factors for bipolar mood disorders.
These findings suggest that miR135 could be a useful therapeutic molecule – both as a blood test for depression and related disorders, and as a target whose levels might be raised in patients. Yeda Research and Development Co. Ltd., the technology transfer arm of the Weizmann Institute, has applied for a patent connected to these findings and recently licensed the rights to miCure Therapeutics to develop a drug and diagnostic method. After completing preclinical trials, the company hopes to begin clinical trials in humans.
Psilocybin inhibits the processing of negative emotions in the brain
When emotions are processed in a negatively biased manner in the brain, an individual is at risk to develop depression. Psilocybin, the bioactive component of the Mexican magic mushroom, seems to intervene positively in the emotion-processing mechanism. Even a small amount of the natural substance attenuates the processing of negative emotions and brightens mood as shown by UZH researchers using imaging methods.
Emotions like fear, anger, sadness, and joy enable people to adjust to their environment and react flexibly to stress and strain and are vital for cognitive processes, physiological reactions, and social behaviour. The processing of emotions is closely linked to structures in the brain, i.e. to what is known as the limbic system. Within this system the amygdala plays a central role – above all it processes negative emotions like anxiety and fear. If the activity of the amygdala becomes unbalanced, depression and anxiety disorders may develop.
Researchers at the Psychiatric University Hospital of Zurich have now shown that psilocybin, the bioactive component in the Mexican magic mushroom, influences the amygdala, thereby weakening the processing of negative stimuli. These findings could “point the way to novel approaches to treatment” comments the lead author Rainer Krähenmann on the results which have now been published in the renowned medical journal “Biological Psychiatry”.
Psilocybin inhibits the processing of negative emotions in the amygdala
The processing of emotions can be impaired by various causes and elicit mental disorders. Elevated activity of the amygdala in response to stimuli leads to the neurons strengthening negative signals and weakening the processing of positive ones. This mechanism plays an important role in the development of depression and anxiety disorders. Psilocybin intervenes specifically in this mechanism as shown by Dr. Rainer Krähenmann’s research team of the Neuropsychopharmacology and Brain Imaging Unit led by Prof. Dr. Franz Vollenweider.
Psilocybin positively influences mood in healthy individuals. In the brain, this substance stimulates specific docking sites for the messenger serotonin. The scientists therefore assumed that psilocybin exerts its mood-brightening effect via a change in the serotonin system in the limbic brain regions. This could, in fact, be demonstrated using functional magnetic resonance imaging (fMRI). “Even a moderate dose of psilocybin weakens the processing of negative stimuli by modifying amygdala activity in the limbic system as well as in other associated brain regions”, continues Krähenmann. The study clearly shows that the modulation of amygdala activity is directly linked to the experience of heightened mood.
Next study with depressive patients
According to Krähenmann, this observation is of major clinical importance. Depressive patients in particular react more to negative stimuli and their thoughts often revolve around negative contents. Hence, the neuropharmacologists now wish to elucidate in further studies whether psilocybin normalises the exaggerated processing of negative stimuli as seen in neuroimaging studies of depressed patients - and may consequently lead to improved mood in these patients.
Rainer Krähenmann considers research into novel approaches to treatment very important, because current available drugs for the treatment of depression and anxiety disorders are not effective in all patients and are often associated with unwanted side effects.
(Source: mediadesk.uzh.ch)