Severe airway inflammation hampers the ability of mice to discern when dangerous situations are no longer a threat, indicating that lung conditions may influence emotions and behaviors. This connection between lung health and brain function could clarify why a small number of individuals who undergo trauma develop post-traumatic stress disorder (PTSD).

“While many people encounter trauma, only 5-10% ultimately develop PTSD,” explains Renu Sah from the University of Cincinnati in Ohio. Prior research has indicated that lung inflammation might be a contributing factor. For instance, individuals with PTSD are approximately eight times more likely to have asthma.

Sah and her team delved deeper into the correlation by observing eight mice exhibiting severe asthma-like symptoms. Their lungs were exposed to mites, inducing an allergic response and subsequent inflammation. Three days afterward, the mice were placed in cages and subjected to three mild electric shocks.

Over the subsequent six days, researchers returned the mice to the cage for five minutes daily, monitoring the duration they stood frozen in fear. On average, these mice were immobilized for about 40% of the final session, which was twice as long compared to another group of 11 mice without lung inflammation who faced the same electrocution.

The two groups did not exhibit differences in fear response the day after the shocks. However, the first group’s prolonged fear response after several days suggests that significant airway inflammation hampers the brain’s ability to recognize when a threat has subsided. “In PTSD patients, this process is dysfunctional, leading to persistent fear memories,” Sah elucidates.

The experiment was replicated with another set of mice experiencing severe lung inflammation, but this time, a medication inhibiting an inflammatory molecule called interleukin-17a was administered. During their final session in the previously shocked cage, these mice displayed about half the freezing response of those that did not receive the medication.

Further analysis revealed that immune cells in brain regions known as subcutaneous organs have receptors for this inflammatory molecule. Unlike most brain areas, subcutaneous organs lack a blood-brain barrier, a protective layer that limits substance exchange between blood and neurons. Consequently, it serves as a “window to the brain,” allowing it to monitor bodily changes and respond accordingly, according to Sah.

The team discovered that immune cells in this region sense inflammatory signals from the lungs, activating adjacent neurons that relay information to the cerebral cortex, a brain region associated with threat recognition.

Using a specialized compound known as chemogenetics, researchers inhibited this signaling pathway in mice with severe lung inflammation, resulting in a notable decrease in their freezing behavior post-shock.

“In essence, severe lung inflammation can impact higher cognitive functions and the ability to navigate traumatic experiences,” asserts Sah. She posits that similar pathways likely exist in humans, as the brain circuits regulating fear are comparable across species.

Other studies suggest that chronic psychological stress diminishes immune responses. Sah speculates that a heightened immune response, in turn, impairs cognitive functions such as the recognition of a threat’s resolution, possibly due to the body reallocating resources from the brain to combat lung issues.

“This research is crucial for understanding the connection between the body and mind,” states Douglas Vanderbilt from Los Angeles Children’s Hospital. He further discusses how his research indicated that children with severe asthma exhibit more pronounced PTSD symptoms. “What we’re uncovering suggests that these brain-body interactions are intricate, so this is likely not the only pathway,” he notes, pointing out that psychological stress from asthma attacks could also influence PTSD risk.

Sah emphasizes that this pathway might vary in women, as only male mice were utilized in her study, suggesting potential differences across genders that warrant additional investigation.

Ultimately, these discoveries may enhance our ability to identify individuals more susceptible to PTSD. For instance, medical professionals might consider screening children with severe asthma for mental health issues, as proposed by Vanderbilt. He further suggests that this line of research could lead to innovative PTSD treatments, such as immunotherapy aimed at reducing inflammation.