Mouse Study: How Fear Turns Into Chronic Anxiety
In a new study, researchers wanted to better understand how fear from a frightening event can evolve into chronic anxiety in some individuals.
“Until now, psychiatrists had little information about what goes on in the brain after a fearful experience, and why some people don’t easily recover and remain anxious, for even as long as the rest of their lives,” says team leader Elaine L. Bearer, MD, PhD, from the University of New Mexico (UNM).
The goal of the study was to shed light on the brain’s response to fear and why, in some cases, it can lead to prolonged anxiety states like post-traumatic stress syndrome (PTSD).
While studying a mouse model, the researchers found that brain activity in anxiety is not the same as in an acute fear response. During anxiety, neural activity is heightened across many specific regions of the brain, and normal coordination between regions is lost.
While not applicable in human subjects, fear can be provoked in rodents by exposure to a frightening smell, such as a product commonly used to protect barbecue grills from mouse nesting. This distinct smell mimics a predator odor and scares mice away.
The research team used this trick to study how the brain responds to frightening events and discover how brain activity evolves from a scary feeling into anxiety.
In a paper published in the journal NeuroImage, the researchers report a link between behavior and brain activity by watching behavior and capturing magnetic resonance images before, during and after exposure to non-scary and scary smells.
They created vulnerability to anxiety by manipulating the serotonin transporter (SERT), which is the major target of psychoactive drugs, like cocaine, and antidepressants, like Prozac. Deletion of the SERT gene (SERT-KO) produces vulnerability to anxiety, and thus provides a unique model to learn how frightening experiences morph into anxiety.
The team compared behavior and brain activity in normal versus SERT-KO to see what happens in the brain during anxiety — those regions active in anxious SERT-KOs and not in normal subjects.
The team used manganese, a non-toxic ion that lights up active neurons in magnetic resonance images. Computational analyses of the images revealed maps of activity throughout the brain before, immediately and long after brief exposure to the scary smell.
The researchers found differences in neural activity in 45 sub-regions throughout the brain. Some regions were activated by the scary smell, and some only came on later. Vulnerability to anxiety was associated with much more activity in many more regions.
The function of some of these regions, including the amygdala and hypothalamus, is at least partly understood, but others, such as the reward circuitry, were not previously known to be involved in anxiety.
In addition, the coordination between regions was altered during states of anxiety, which may represent a brain-wide signature of anxiety, or signify a discoordination between brain regions, which is often experienced when we are frightened or anxious.
“We now know that brain activity in anxiety is not the same as in an acute fear response,” Bearer says. “With anxiety, neural activity is elevated across many specific regions of the brain, and normal coordination between regions is lost.”
The time lag for resilient or anxious outcomes suggests that early containment of fearful responses may reduce the likelihood of progression to anxiety.
The involvement of serotonin also suggests drug targets that could help in reducing the likelihood of anxiety. Meditation, music, poetry, exercise and other stress-reducing activities that engage the reward circuitry may also help. Early interventions will have lasting benefits.
Bearer conducted the study with graduate student Taylor W. Uselman.
Pedersen, T. (2020). Mouse Study: How Fear Turns Into Chronic Anxiety. Psych Central. Retrieved on August 15, 2020, from https://psychcentral.com/news/2020/07/17/mouse-study-how-fear-turns-into-chronic-anxiety/158033.html