Tuesday May 27 2014
Traumatic events can trigger post-traumatic stress disorder
"A drug could be re-purposed to erase painful memories from people who have suffered trauma and pain," The Independent reports. The news comes from a study involving mice which measured their response to a series of electric shocks.
The mice were either fed the drug fingolimod, which is used to treat multiple sclerosis, or a saline placebo daily. The researchers then performed their experiment over the course of three days.
On the first day, the mice were given a mild electric shock when they were put in an experimental chamber. The next day they were put in the chamber and no shock was given, but the mice expected to have a shock and still froze in fear.
The researchers found that the fingolimod mice were no longer scared of being in the chamber and did not freeze. However, the placebo mice were still scared and froze. This suggests that fingolimod may help "erase" memories associated with fear, pain and trauma when they are no longer needed.
Most of us have memories that we would rather forget, such as an embarrassing incident at an office party. But some incidents can be so traumatic that they become lodged in the mind and trigger conditions such as post-traumatic stress disorder. A drug that could help erase such memories could prove very useful.
This is interesting early-stage research, but much more research is required before fingolimod can be considered for use as a treatment for post-traumatic stress disorder or other anxiety disorders.
Where did the story come from?
The study was carried out by researchers from Virginia Commonwealth University School of Medicine in the US and the Chinese Academy of Sciences. It was funded by the US National Institutes of Health and the National Natural Science Foundation of China.
The study was published in the peer-reviewed journal, Nature Neuroscience.
While The Independent and the Mail Online's reporting of the study was accurate, both organisations chose to only focus on the experiment involving electric shocks. Other aspects of the study were ignored.
What kind of research was this?
This was laboratory and animal-based research into a drug called fingolimod, which is used in the treatment of multiple sclerosis.
NICE recommends its use in the treatment of some people with relapsing-remitting multiple sclerosis. This form of multiple sclerosis is where patients have an unchanged or increased relapse rate, or ongoing severe relapses in comparison with the previous year, despite taking drugs called beta interferons.
The researchers say that fingolimod has potential central nervous system benefits that are not yet fully understood.
What did the research involve?
The researchers performed a series of experiments on cells they cultured (grew) in the laboratory, as well as on mice.
The news coverage concentrated on one experiment the researchers performed, which aimed to see whether fingolimod affected contextual fear conditioning and fear extinction.
Contextual fear conditioning is a process by which an organism learns to associate a neutral context – in this case an experimental chamber – with an adverse event, such as an electric shock.
Essentially, the experiment made use of the classic Pavlovian response, where behaviour is conditioned in response to an external stimulus. In this case, the response to the electric shock caused the mice to "freeze", where they don't move other than to breathe.
The researchers fed the mice fingolimod or saline (placebo) and monitored their freezing behaviour before and after placing them in an experimental chamber and giving them an electrical shock. They then returned the mice to their normal cages.
Two days later, the mice were returned to the experimental chamber and the freezing behaviour was monitored again to see if mice receiving fingolimod or saline froze for different amounts of time.
The researchers performed all of these experiments on mice that had been genetically modified so that they lacked part of their immune system. This is because fingolimod is known to affect the immune system, and the immune system has an effect on memory and learning.
What were the basic results?
The researchers performed a series of laboratory experiments and found that fingolimod becomes modified when it enters the cell. This modified form inhibits the activity of a class of enzymes, which in turn has multiple effects on gene expression (gene activity).
The researchers also discovered that fingolimod accumulates in the brains of mice, including part of the brain called the hippocampus, which is involved in memory formation.
They found that there was no significant difference in fear contextual conditioning between mice receiving fingolimod or saline – in other words, both sets of mice did not forget the association between the experimental chamber and the electric shock.
Mice receiving fingolimod or saline did have a significant difference in contextual fear extinction. The mice had similar freezing behaviour when they received the electric shock on the first day. They also had similar freezing behaviour on the second day, when they were put into the experimental chamber without receiving a shock, with both groups of mice gradually freezing less.
However, when they were put into the chamber on the third day, the mice fed fingolimod maintained low levels of freezing, showing that they were no longer afraid of being in the chamber, while mice fed the placebo froze.
How did the researchers interpret the results?
The researchers concluded that fingolimod "may be a useful adjuvant therapy to facilitate extinction of aversive memories".
Despite what the media has reported, the evidence from this study does not prove that it is possible to "erase" painful memories in humans. All we can safely say is that this study has found that the drug fingolimod can reduce fear-related behaviour in genetically modified mice with defects in their immune system.
These mice are known to have impaired acquisition and ability to perform cognitive tasks. Whether fingolimod would have a similar effect on humans who did not have an impaired immune system or cognitive function is unknown.
Changes in memory and anxiety levels were not reported in any of the human clinical trials of fingolimod used in the treatment of multiple sclerosis. There were many listed side effects, including headaches affecting 1 in 10 people, and depression affecting between 1 in 10 and 1 in 100 people. This means that the risks of taking fingolimod solely as an anti-anxiety drug may well outweigh any benefits.
If you are troubled by traumatic events in your past, ask your GP for advice. Many people with post-traumatic stress disorder respond well to a combination of medication and talking therapies such as cognitive behavioural therapy.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.