With altered brain chemistry, fear is more easily overcome

June 12, 2012

Researchers at Duke University and the National Institutes of Health have found a way to calm the fears of anxious mice with a drug that alters their brain chemistry. They've also found that human genetic differences related to the same brain chemistry influence how well people cope with fear and stress.

It's an advance in understanding the brain's circuitry that the research team says may hold particular promise for people at risk for , including those suffering ().

"What is most compelling is our ability to translate first from mice to human neurobiology and then all the way out to ," said Ahmad Hariri, a at the Duke Institute for & Policy. "That kind of translation is going to define the future of psychiatry and neuroscience."

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 endocannabinoid chemical in the brain that acts in essentially the same way that Cannabis, aka marijuana, does (hence the name endocannabinoid).

Earlier studies had suggested that blocking the FAAH enzyme could decrease fear and anxiety by increasing endocannabinoids. (That's 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 endocannabinoid 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, 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 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 (http://dunedinstudy.otago.ac.nz/), 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 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."

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.

Explore further: Researchers pinpoint genetic connection to traumatic experience

More information: "Convergent Translational Evidence of a Role for Anandamide in Amygdala-Mediated Fear Extinction, Threat Processing and Stress-Reactivity," O Gunduz-Cinar, KP MacPherson et al. Molecular Psychiatry, June 12th. doi:10.1038/mp.2012.72

Related Stories

Researchers pinpoint genetic connection to traumatic experience

February 1, 2012
Rutgers scientists have uncovered genetic clues as to why some mice no longer in danger are still fearful while others are resilient to traumatic experiences – knowledge that could help those suffering with crippling ...

Study offers new insight for preventing fear relapse after trauma

November 29, 2011
(Medical Xpress) -- In a new study, University of Michigan researchers identified brain circuits in rats that are responsible for the return of fear after it has been suppressed behaviorally.

Recommended for you

Probing how Americans think about mental life

October 20, 2017
When Stanford researchers asked people to think about the sensations and emotions of inanimate or non-human entities, they got a glimpse into how those people think about mental life.

Itsy bitsy spider: Fear of spiders and snakes is deeply embedded in us

October 19, 2017
Snakes and spiders evoke fear and disgust in many people, even in developed countries where hardly anybody comes into contact with them. Until now, there has been debate about whether this aversion is innate or learnt. Scientists ...

Inflamed support cells appear to contribute to some kinds of autism

October 18, 2017
Modeling the interplay between neurons and astrocytes derived from children with Autism Spectrum Disorder (ASD), researchers at University of California San Diego School of Medicine, with colleagues in Brazil, say innate ...

Study suggests psychedelic drugs could reduce criminal behavior

October 18, 2017
Classic psychedelics such as psilocybin (often called magic mushrooms), LSD and mescaline (found in peyote) are associated with a decreased likelihood of antisocial criminal behavior, according to new research from investigators ...

Taking probiotics may reduce postnatal depression

October 18, 2017
Researchers from the University of Auckland and Otago have found evidence that a probiotic given in pregnancy can help prevent or treat symptoms of postnatal depression and anxiety.

Schizophrenia disrupts the brain's entire communication system, researchers say

October 17, 2017
Some 40 years since CT scans first revealed abnormalities in the brains of schizophrenia patients, international scientists say the disorder is a systemic disruption to the brain's entire communication system.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.