SPOILER ALERT! ~ The locus coeruleus (LC) is a small nucleus located at the base of the brain ~ Its function it is to modulate vigilance and alertness in the present of a threat ~ The LC affects our attention and alertness through the release of norepinephrine ~ Higher brain structures (those involved in reasoning and judgment) regulate the activity of the LC by analyzing and estimating the level of danger. ~ Chronic stress increases activity of the LC thereby producing pathological anxiety
Pathological anxiety is defined as a state of persistent fear-like behavior in the absence of threat. It is a core feature of anxiety disorders including generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD) and panic disorder (PD).
At the source of that anxiety is the locus coeruleus (LC), a small nucleus located at the base of the brain, which is activated by threats and stressors. Its function is to modulate behavior and arousal states (e.g., vigilance, alertness) through the release of norepinephrine (NE).
The LC Responds to Threats
Receptors in the LC are constantly active (i.e., called tonic receptors), but their activity is low during sleep, intermediate during waking hours, and high during anxiety and distress.
Typically, a normal response to a threatening situation can be freezing or immobility as a behavioral reflex to a changing environment. Higher cortical structures (i.e., brain structures that are involved in decision, judgment, and reasoning) on the other hand stop or regulate that behavior based on whether or not the threat poses an immediate danger and the degree of that danger.
The activity of the LC is part of the behavioral reflex that occurs immediately after the perception of a threat. It modulates attention and vigilance to draw our focus towards the threat. In fact, the LC responds to anything new in our environment and changes our level of attention and arousal according to whether or not there is danger.
Overactive LC in Anxiety
This is an adaptive response that usually habituates (i.e., it does not stimulate brain cells as much as it did the first time) over time if the stimulus is not threatening, which results in lowered vigilance and our attention is switched elsewhere.
However, chronic stress disrupts this adaptive response by increasing the LC reactivity. Particularly, not only does chronic stress amplifies the LC response to threat, but it also increases LC sensitivity to stress.
There is evidence showing that increased LC activity produces greater anxiety and fear-like behaviors in both animals and humans. For example, a number of studies report that increased stimulation of the LC appears to be sufficient to induce anxiety after being exposed to stress.
Further support comes from findings showing that LC lesions (i.e., wounds), which results in reduced activity seem to reduce anxiety or fear-like behaviors. A few risk factors for the development of pathological anxiety have been identified such as being a female, chronic alcohol administration and inflammation
Morris, L. S., McCall, J. G., Charney, D. S., & Murrough, J. W. (2020). The role of the locus coeruleus in the generation of pathological anxiety. Brain and neuroscience advances, 4, 2398212820930321. https://doi.org/10.1177/2398212820930321