Posts tagged fear extinction
Articles and news from the latest research reports.
L-dopa medication could be helpful in the treatment of phobias and post-traumatic stress disorder
A drug used to treat Parkinson’s disease could also help people with phobias or post-traumatic stress disorder (PTSD). Scientists of the Translational Neurosciences (FTN) Research Center at Johannes Gutenberg University Mainz (JGU) are currently exploring the effects of psychotherapy to extinguish fears in combination with L-dopa. This drug does not only help movement disorders, but might also be used to override negative memories.
Professor Raffael Kalisch, head of the Neuroimaging Center (NIC) of the JGU Translational Neurosciences Research Center, and his collaborators at the University of Innsbruck are conducting research in mice and in humans into the psychological and neurobiological mechanisms of anxiety and fear. “Fear reactions are essential to health and survival, but the memories of angst-inducing situations may cause long-term anxiety or phobias,” explained Kalisch. In psychotherapy, the ’fear extinction’ method is used in exposing people to a threat but without the adverse consequences. Latest research has proven that extinguishing fear also predicts mental health after trauma, suggesting extinction may be an important resilience mechanism.
Fear extinction involves a person being presented with a neutral stimulus, such as a circle on a screen, together with a painful sensation. Soon the person predicts pain in response to the circle on the screen and fear becomes conditioned. Then the person is shown the circle again, but this time without the painful stimulus, so that the person can disassociate the two factors. A person who is afraid of spiders, for example, will in psychotherapy be confronted with spiders in a way that reassures them that the spider is harmless.
In another research program, Belgian scientists tested the ability to extinguish fear in soldiers later deployed to a war zone and found differences in the soldiers’ resilience to traumatic memories. Some experienced post-traumatic stress symptoms following their deployment, whereas those who were able to extinguish fear in the laboratory maintained a good state of mental health. “If you are mentally flexible enough to change the associations that your mind has created, you might be better able to avoid lasting damage,” explained Kalisch. In cooperation with other scientists, Kalisch has found first evidence that this process of changing negative associations might involve the brain’s systems for reward and pleasure and depend on release of the neurotransmitter dopamine that helps control them.
However, even after successful extinction, old fear associations can return under other stressful circumstances. This might involve the development of PTSD or a relapse after successful psychotherapy. Kalisch has found that L-dopa, a drug to treat Parkinson’s disease, can prevent this effect and could therefore possibly be used to prevent relapse in treated PTSD or phobia patients. L-dopa is taken up by the brain and transformed into dopamine that not only controls the brain’s reward and pleasure centers and helps regulate movement, but also affects memory formation. The person receiving L-dopa after extinction will thus create a stronger secondary positive memory of the extinction experience and will thus be able to more easily replace the negative memory. This raises new questions about the role of primary fear memories and secondary prevention by L-dopa. “We would like to be able to enhance the long-term effects of psychotherapy by combining it with L-dopa,” said Professor Raffael Kalisch. To this end, he is about to start a clinical study of people with a spider phobia to determine the effects of L-dopa on therapy outcome. “Manipulating the dopamine system in the brain is a promising avenue to boost primary and secondary preventive strategies based on the extinction procedure,” he continued.
Publication:
Raczka, K. A. et al. (2011), Empirical support for an involvement of the mesostriatal dopamine system in human fear extinction, Translational Psychiatry 1:e12
Haaker, J. et al. (2013), Single dose of L-dopa makes extinction memories context-independent and prevents the return of fear, PNAS Plus - Biological Sciences - Psychological and Cognitive Sciences 110 (26): E2428-36
(Source: uni-mainz.de)
Controlling fear by modifying DNA
For many people, fear of flying or of spiders skittering across the lounge room floor is more than just a momentary increase in heart rate and a pair of sweaty palms.
It’s a hard-core phobia that can lead to crippling anxiety, but an international team of researchers, including neuroscientists from The University of Queensland’s Queensland Brain Institute (QBI), may have found a way to silence the gene that feeds this fear.
QBI senior research fellow Dr Timothy Bredy said the team had shed new light on the processes involved in loosening the grip of fear-related memories, particularly those implicated in conditions such as phobia and post-traumatic stress disorder.
Dr Bredy said they had discovered a novel mechanism of gene regulation associated with fear extinction, an inhibitory learning process thought to be critical for controlling fear when the response was no longer required.
“Rather than being static, the way genes function is incredibly dynamic and can be altered by our daily life experiences, with emotionally relevant events having a pronounced impact,” Dr Bredy said.
He said that by understanding the fundamental relationship between the way in which DNA functions without a change in the underlying sequence, future targets for therapeutic intervention in fear-related anxiety disorders could be developed.
“This may be achieved through the selective enhancement of memory for fear extinction by targeting genes that are subject to this novel mode of epigenetic regulation,” he said.
Mr Xiang Li, a PhD candidate and the study’s lead author, said fear extinction was a clear example of rapid behavioural adaptation, and that impairments in this process were critically involved in the development of fear-related anxiety disorders.
“What is most exciting is that we have revealed an epigenetic state that appears to be quite specific for fear extinction,” Mr Li said.
Dr Bredy said this was the first comprehensive analysis of how fear extinction was influenced by modifying DNA.
“It highlights the adaptive significance of experience-dependent changes in the chromatin landscape in the adult brain,” he said.
The collaborative research is being done by a team from QBI, the University of California, Irvine, and Harvard University.
The study was published this month in the Proceedings of the National Academy of Sciences of the United States of America.
Study reveals potential target to better treat, cure anxiety disorders
Researchers at Boston University School of Medicine (BUSM) have, for the first time, identified a specific group of cells in the brainstem whose activation during rapid eye movement (REM) sleep is critical for the regulation of emotional memory processing. The findings, published in the Journal of Neuroscience, could help lead to the development of effective behavioral and pharmacological therapies to treat anxiety disorders, such as post-traumatic stress disorder, phobias and panic attacks.
There are two main stages of sleep – REM and non-REM – and both are necessary to maintain health and to regulate multiple memory systems, including emotional memory. During non-REM sleep, the body repairs tissue, regenerates cells and improves the function of the body’s immune system. During REM sleep, the brain becomes more active and the muscles of the body become paralyzed. Additionally, dreaming generally occurs during REM sleep, as well as physiological events including saccadic eye movements and rapid fluctuations of respiration, heart rate and body temperature. One particular physiological event, which is a hallmark sign of REM sleep, is the appearance of phasic pontine waves (P-waves). The P-wave is a unique brain wave generated by the activation of a group of glutamatergic cells in a specific region within the brainstem called the pons.
Memories of fearful experiences can lead to enduring alterations in emotion and behavior and sleep plays a natural emotional regulatory role after stressful and traumatic events. Persistence of sleep disturbances, particularly of REM sleep, is predictive of developing symptoms of anxiety disorders. A core symptom of these disorders frequently reported by patients is the persistence of fear-provoking memories that they are unable to extinguish. Presently, exposure therapy, which involves controlled re-exposure to the original fearful experience, is considered one of the most effective evidence-based treatments for anxiety disorders. Exposure therapy produces a new memory, called an extinction memory, to coexist and compete with the fearful memory when the fearful cue/context is re-encountered.
The strength of the extinction memory determines the efficacy of exposure therapy. A demonstrated prerequisite for the successful development of an extinction memory is adequate sleep, particularly REM sleep, after exposure therapy. However, adequate or increased sleep alone does not universally guarantee its therapeutic efficacy.
"Given the inconsistency and unpredictability of exposure therapy, we are working to identify which process(es) during REM sleep dictate the success or failure of exposure therapy," said Subimal Datta, PhD, director and principle investigator at the Laboratory of Sleep and Cognitive Neuroscience at BUSM who served as the study’s lead author.
The researchers used contextual fear extinction training, which works to turn off the conditioned fear, to study which brain mechanisms play a role in the success of exposure therapy. The study results showed that fear extinction training increased REM sleep. Surprisingly, however, only 57 percent of subjects retained fear extinction memory, meaning that they did not experience the fear, after 24 hours. There was a tremendous increase of phasic P-wave activity among those subjects. In 43 percent of subjects, however, the wave activity was absent and they failed to retain fear extinction memory, meaning that they re-experienced fear.
"The study results provide direct evidence that the activation of phasic P-wave activity within the brainstem, in conjunction with exposure therapy, is critical for the development of long-term retention of fear extinction memory," said Datta, who also is a professor of psychiatry and neurology at BUSM. In addition, the study indicates the important role that the brainstem plays in regulating emotional memory.
Future research will explore how to activate this mechanism in order to help facilitate the development of new potential pharmacological treatments that will complement exposure therapy to better treat anxiety and other psychological disorders.
According to the National Institute of Mental Health, anxiety disorders affect approximately 40 million American adults each year. While anxiety can sometimes be a normal and beneficial reaction to stress, some people experience excessive anxiety that they are unable to control, which can negatively impact their day to day life.
(Source: eurekalert.org)