PTSD: Anti-anxiety Drug Calms Fears by Altering Brain Chemistry

An advance in understanding the brain’s fear circuitry has been revealed by a research team. They say it may hold particular promise for people at risk for anxiety disorders, including those suffering post-traumatic stress disorder (PTSD). Findings are reported in the journal Molecular Psychiatry.

“What is most compelling is our ability to translate first from mice to human neurobiology and then all the way out to human behaviour,” says Ahmad Hariri, a neurobiologist at Duke University. “That kind of translation is going to define the future of psychiatry and neuroscience.”

Read the original study DOI: 10.1038/mp.2012.72

 

The common thread in their studies is a gene encoding an enzyme called fatty acid amide hydrolase, or FAAH.

The enzyme breaks down a natural endo-cannabinoid chemical in the brain that acts in essentially the same way that Cannabis, aka marijuana, does (hence the name endo-cannabinoid).

Earlier studies had suggested that blocking the FAAH enzyme could decrease fear and anxiety by increasing endo-cannabinoids, which is consistent with the decreased anxiety some experience after smoking marijuana.

In 2009, Hariri’s lab found that a common variant in the human FAAH gene leads to decreased enzyme function with affects on the brain’s circuitry for processing fear and anxiety.

In the new study, Andrew Holmes’ group at the National Institute on Alcoholism and Alcohol Abuse tested the effects of a drug that blocks FAAH activity in fear-prone mice that had also been trained to be fearful through experiences in which they were delivered foot shocks.

Tests for the ability of those mice to get over their bad experiences found that the drug allowed a faster recovery from fear thanks to higher brain endo-cannabinoid levels.

More specifically, the researchers showed that those drug effects traced to the amygdala, a small area of the brain that serves as a critical hub for fear processing and learning.

To test for the human relevance of the findings, Hariri’s group went back to the genetic variant they had studied earlier in a group of middle-aged adults.

They showed study participants a series of pictures depicting threatening faces while they monitored the activity of their amygdalas using functional magnetic resonance imaging (fMRI) scans. They then looked for how the genetic variant affected this activity.

While the activity of the amygdala in all participants decreased over repeated exposures to the pictures. But people who carried the version of the FAAH gene associated with lower enzyme function and higher endo-cannabinoid levels showed a greater decrease in activity.

Hariri says that suggests that those individuals may be better able to control and regulate their fear response.

Further confirmation came from an analysis led by Duke’s Avshalom Caspi and Terrie Moffitt of 1,000 individuals in the Dunedin Study, who have been under careful observation since their birth in the 1970s in New Zealand.

Consistent with the mouse and brain imaging studies, those New Zealanders carrying the lower-expressing version of the FAAH gene were found to be more likely to keep their cool under stress.

“This study in mice reveals how a drug that boosts one of the brain’s naturally occurring endo-cannaboids enables fear extinction, a process that forms the basis of exposure therapy for PTSD,” Holmes says.

“It also shows how human gene variation in the same chemical pathways modulates the amygdala’s processing of threats and predicts how well people cope with stress.”

Studies are now needed to further explore both the connections between FAAH variation and PTSD risk as well as the potential of FAAH inhibition as a novel therapy for fear-related disorders, the researchers say.

More news from Duke University: http://today.duke.edu/

Sleep: Accentuating the positive memories

Sleep plays a powerful role in preserving our memories, but while recent research shows that wakefulness may cloud memories of negative or traumatic events, a new study has found that wakefulness also degrades positive memories.

Sleep, it seems, protects positive memories just as it does negative ones, and that has important implications for the treatment of post-traumatic stress disorder (PTSD).

“The study of how sleep helps us remember and process emotional information is still young,” says Alexis Chambers of the University of Notre Dame.

Past work has focused on the role of negative memories for sleep, in particular how insomnia is a healthy biological response for people to reduce negative memories and emotions associated with a traumatic event.

Two new studies presented this week at a meeting of cognitive neuroscientists in Chicago are exploring the flip side: how sleep treats the positive.

“Only if we investigate all the possibilities within this field will we ever fully understand the processes underlying our sleep, memory, and emotions,” Chambers says.

Protecting the positive

To test how sleep affects positive memories, Rebecca Spencer of the University of Massachusetts, Amherst, and her colleagues split 70 young adults into two groups, one that got to sleep overnight and one that had to stay awake.

Both groups viewed images of positive items, such as puppies and flowers, and neutral items, such as furniture or dinner plates.

The researchers then tested the participants’ memories of and emotional reactions to the images 12 hours later, after either the period of sleep or wake.

They found that “sleep enhances our emotionally positive memories while these memories decay over wake,” Spencer says.

“Positive memories may even be prioritized for processing during sleep.” But while people remembered the positive images more than the neutral ones, their emotional response to the positive images did not change over sleep versus wake.

“It doesn’t matter if you went to sleep or stayed awake, what you thought was a ’9′ i.e. really great, you still think is a ’9′,” she says.

The results, she says, could have significant implications for treating post-traumatic stress disorder, as using wakefulness could have the unintended effect of degrading of positive memories in addition to negative memories.

“It suggests that insomnia should be treated at some point after a traumatic event – perhaps a few days/weeks depending on the level of trauma, so that these positive memories can be strengthened and eventually outweigh the negative,” Spencer says.

Read more: Accentuating the positive memories for sleep | ScienceBlog.com