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Anxiety is an emotion that is central to human experience which can also cause immense suffering for millions of children and adults when it goes awry. A new study published in the Journal of Neuroscience looked at the biological roots of anxiety.

“Anxiety disorders are the most common family of mental illnesses, and they impose a staggered burden on global public health and the economy,” study author Alexander J. Shackman told us. “For instance, they are consistently ranked among the top ten causes of disability throughout most of the world, including the United States, and for individuals with moderate to severe disorders they can be as debilitating as many serious physical disorders (e.g. COPD, cancer).”

Existing treatments are inconsistently effective or, in the case of pharmacological treatments, are associated with significant side effects.

“These kinds of epidemiological data underscore the urgency of developing a deeper understanding of the underlying neural circuitry,” Shackman told us. “Among brain imagers and clinicians, it is widely through that anxiety disorders reflect two phenomenologically and neuroanatomically distinct processes.”

The first process is fear, an intense, fleeting reaction to immediate danger.

“For example, the stick you were about to step on is, in fact, a snake; a car suddenly veers toward you as you are navigating the Beltway; you have social anxiety disorder and the instructor singles you out to answer a question or perform a demo in front of your classmates,” Shackman explains.

The second process is anxiety, a less-intense, but sustained state of heightened arousal, anticipatory apprehension, and vigilance elicited by uncertain danger.

“For example, walking through a bad neighborhood in DC at night; hiking in an area where cougars have been spotted recently; contemplating whether you really want to take a spin on the Beltway; an individual with social anxiety contemplating the school day ahead of them over breakfast,” Shackman told us. “In each of these examples, there is the possibility of harm, but the agent is uncertain about its nature (What/Who will attack?), intensity (How bad will it be?), likelihood (Is today a lucky or unlucky day?), or timing (When will it strike?).”

While this conceptual distinction dates back to the time of Freud or earlier, in more recent years it has been suggested that fear and anxiety reflect the operation of non-overlapping brain circuits, with fear orchestrated by the amygdala in the brain, and anxiety triggered by a neighboring subcortical structure, the Bed Nucleus of the Stria Terminalis.

The current study was focused on understanding the neural circuitry responsive to different kinds of threat and to determine the degree to which certain and uncertain threat recruit shared versus distinct brain circuits.

“There were two competing predictions,” Shackman told us. “On the one hand, it is widely believed that certain and uncertain threat are processed by strictly segregated brain circuits that, ultimately, give rise to feelings of fear and anxiety. On the other hand, my colleagues and I have spent the last several years raising questions about the evidence for that claim. We anticipated that the two circuits would show substantial overlap.”

Researchers used a combination of techniques, including neuroimaging measures of brain function (fMRI), psychophysiological measures of visceral arousal, and self-report measures of subjective distress.

“The results suggest that --- at least when viewed through the lens of fMRI --- waiting for a threat, whether certain or uncertain, was associated with a remarkably similar network of brain regions,” Shackman told us. “Taken with other evidence emerging from mechanistic studies of rodents and monkeys, these results suggest that fear and anxiety reflect a largely overlapping set of neural building blocks. This runs counter to the dominant theoretical narrative, and suggests the need to revamp models, like the U.S. NIMH RDoC framework, that imply a strict segregation of fear and anxiety in the brain.”

Shackman’s hope is that work like this will provide a clearer understanding of how emotions are orchestrated by the brain and, ultimately, accelerate the development of more effective treatments for the millions of children and adults around the world who suffer from extreme fear and anxiety.