Seven to eight percent of the population will suffer from the nightmares and flashbacks of PTSD at some point in their lives. Post-traumatic stress disorder often affects soldiers who have been through combat, but can be caused by countless other stressful or frightening events, like muggings or natural disasters. However, a new study from MIT has made serious in-roads into what leads to its development—and maybe even how to keep it from happening at all.
One of the biggest known risk factors for PTSD is chronic stress, or feeling overwhelmed, worried, or run-down for an extended period of time. The researchers confirmed previous studies with their own: The mice who underwent chronic stress prior to a traumatic experience used the pathway that ingrains traumatic memories more strongly than the stress-free animals.
Thus, the idea behind the study was to inhibit this kind of memory formation in the first place to prevent PTSD. “The idea is not to make people amnesic but to reduce the impact of the trauma in the brain by making the traumatic memory more like a ‘normal,’ unintrusive memory,” clarified Ki Goosens, an assistant professor of neuroscience and investigator in MIT’s McGovern Institute for Brain Research, in an MIT press release.
Blame it on the serotonin
The specific pathway of this disease involves a part of the brain known as the amygdala, an almond-sized structure involved in responding to and remembering stress and fear. In mice with chronic stress who experience a trauma, a neurotransmitter known as serotonin acted on the amygdala to promote the process of memory consolidation. (Memory consolidation is the process by which short-term memories are turned into long-term memories.)
When this interaction was inhibited following a trauma, the stressed animals did not exhibit signs of PTSD. Moreover, in the unstressed mice, inhibiting this process after trauma had no effect; PTSD still did not develop.
“That was really surprising to us,” said lead author and MIT postdoc Michael Baratta. “It seems like stress is enabling a serotonergic memory consolidation process that is not present in an unstressed animal.”
Besides stress activating a pathway that can lead to PTSD, it also packs a sort of double-whammy by increasing the number of 5-HT2C receptors in the amygdala. Serotonin (also known by a shortened version of its chemical name, 5-HT) binds to these receptors, activating the memory consolidation process. More receptors leads to more binding, causing stronger memory formation. The researchers believe this may account for the flashbacks in PTSD.
“It’s strengthening the consolidation process so the memory that’s generated from a traumatic or fearful event is stronger than it would be if you don’t have this serotonergic consolidation engaged,” Baratta says.
The good (and bad) news
Memories can take hours or days to become ingrained as long-term memories—but are difficult to erase once they are. However, preventative measures taken immediately following a traumatic event might prevent them from forming as strongly.
“The consolidation process gives us a window in which we can possibly intervene and prevent the development of PTSD. If you give a drug or intervention that can block fear memory consolidation, that’s a great way to think about treating PTSD,” said Goosens. “Such an intervention won’t cause people to forget the experience of the trauma, but they might not have the intrusive memory that is ultimately going to cause them to have nightmares or be afraid of things that are similar to the traumatic experience.”
The consolidation process might not be the only window of opportunity, though. When memories are recalled, there is a certain amount of time in which they could be altered and reconsolidated; so serotonin-blocking drugs could help to weaken already encoded memories.
Even better, there is a candidate drug for just this purpose called agomelatine, which is already FDA-approved for depression.
But there is one major caveat out of this study
Selective serotonin reuptake inhibitors (SSRIs), a current common treatment for PTSD, are probably a very bad idea. SSRIs keep serotonin around brain cells longer by keeping serotonin-producing cells from drawing them back in. So for PTSD patients, these could make memories and flashbacks more ingrained.
“The consolidation of traumatic memories requires this serotonergic cascade and we want to block it, not enhance it,” she adds. “This study suggests we should rethink the use of SSRIs in PTSD and also be very careful about how they are used, particularly when somebody is recently traumatized and their memories are still being consolidated, or when a patient is undergoing cognitive behavior therapy where they’re recalling the memory of the trauma and the memory is going through the process of reconsolidation.”
The paper can be found in the journal Biological Psychiatry.
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Feature image: Thinkstock
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