A deadly coronavirus pandemic, economic instability and civil unrest together will have immense impact on the mental well-being of millions of people, said a new study that highlighted how vulnerable people fear from such frightening events and develop lifelong anxiety.

So far, psychiatrists had little information about what goes on in the brain after a fearful experience, and why some people fail to recover and remain anxious, as long as the rest of their lives. A University of New Mexico research team led by Elaine L. Bearer, the Harvey Family Professor in Pathology, and graduate student Taylor W. Uselman has identified brain-wide neural correlates of the transition from fear to anxiety.

Life-threatening fear frequently leads to post-traumatic stress syndrome (PTSD) and the study focused on brain's response to fear and why, in some cases, it can lead to prolonged anxiety states like PTSD. Based on study of rodents by exposure to a scary smell, such as a product commonly used to protect our barbecues from mouse nesting, it simulated a predator odor and scared mice away.

Coronavirus

The UNM team used this trick to witness how the brain responds to scary events and discover how brain activity evolves from a scary feeling to anxiety and their paper published in the journal NeuroImage, explained a correlation of behavior with brain activity by watching behavior and capturing magnetic resonance images before, during and after exposure to non-scary and scary smells.

Vulnerability to anxiety

For the study, 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 provides a model to learn how frightening experiences morph into anxiety.

Anxiety
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The researchers compared behavior and brain activity in normal versus SERT-KO to identify the neural correlates of anxiety - those regions active in anxious SERT-KOs and not in normal subjects. To highlight active neurons, they used manganese, a non-toxic ion that lights up active neurons in magnetic resonance images. These brain-wide images yielded maps of activity throughout the brain before, immediately and long after brief exposure to the scary smell.

They identified differences in neural activity in 45 sub-regions in the brain, some activated by the scary smell, and some only came on later. Vulnerability to anxiety correlated with much more activity in many more regions, including the amygdala and hypothalamus, and others such as the reward circuitry, previously known to be involved in anxiety.

"We now know that brain activity in anxiety is not the same as in an acute fear response," Bearer said. "With anxiety, neural activity is elevated across many specific regions of the brain, and normal coordination between regions is lost."

What does this mean amid COVID?

The time lag for resilient or anxious outcomes suggests that early containment of fearful responses to surges in cases, protests and economic recession may reduce the likelihood of progression to anxiety. The involvement of serotonin also suggests pharmacologic targets that could help in reducing the likelihood of anxiety.

To reduce anxiety, meditation, music, poetry, exercise and other stress-reducing activities that engage the reward circuitry are likely to help and early interventions will have lasting benefits, said the researchers.