Altering brain chemistry may help overcome fear more easilyPublished On: Wed, Jun 13th, 2012 | Neurobiology | By BioNews
US researchers have found a way to calm the fears of anxious mice with the help of a drug that alters their brain chemistry.
They have also found that human genetic differences related to the same brain chemistry influence the capacity of people to deal with fear and stress.
The research team claims that it’s an advance in understanding the brain’s fear circuitry and may hold particular promise for people at risk for anxiety disorders, including those who are suffering post-traumatic stress disorder (PTSD).
“What is most compelling is our ability to translate first from mice to human neurobiology and then all the way out to human behavior,” Ahmad Hariri, a neurobiologist at the Duke Institute for Genome Sciences and Policy, said.
“That kind of translation is going to define the future of psychiatry and neuroscience.”
The common thread in their studies is a gene, which encodes the enzyme called fatty acid amide hydrolase, or FAAH.
This enzyme breaks down a natural ‘endocannabinoid’ chemical in the brain that acts in basically the same way that Cannabis, aka marijuana, does.
Earlier studies had suggested that blocking the FAAH enzyme could decrease fear and anxiety by increasing ‘endocannabinoid’s.
In 2009, Hariri’s lab found that a common variant in the human FAAH gene leads to decreased enzyme function with influence 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 were trained to be fearful through experiences in which they were delivered foot shocks.
Tests for the ability of those mice to overcome their bad experiences found that the drug allowed a faster recovery from fear thanks to higher brain ‘endocannabinoid’ levels.
More particularly, the researchers showed that the 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 before in a group of middle-aged adults.
They showed the study participants a series of photographes , 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 had affected this activity.
While the activity of the amygdala in all participants went down over repeated exposures to the pictures, people who carried the version of the FAAH gene associated with lower enzyme function and higher ‘endocannabinoid’ levels showed a greater decrease in activity.
Hariri revealed that those people might be better able to control and regulate their fear response.
Further confirmation came from an analysis that is 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 1970s in New Zealand.
Consistent with the mouse and brain imaging studies, the New Zealanders who carried the lower-expressing version of the FAAH gene were found 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 endocannaboids enables fear extinction, a process that forms the basis of exposure therapy for PTSD,” Holmes said.
“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,” he added.