Around twelve years ago, scientists discovered a hormone called ghrelin that influences appetite and earned the nickname “hunger hormone.” Since then, drug companies have sought to target ghrelin for treating obesity, but successful drugs have not been developed yet. However, recent research from MIT neuroscientists reveals that ghrelin’s role extends far beyond hunger regulation. It appears that ghrelin released during chronic stress can make the brain more susceptible to traumatic events, potentially increasing the risk of developing posttraumatic stress disorder (PTSD).
The team found that reducing ghrelin levels through drugs, originally intended for combating obesity, could be beneficial in protecting individuals at high risk for PTSD, such as soldiers in war zones. This approach could involve administering a ghrelin vaccine to individuals before deployment, reducing the incidence of PTSD. Currently, no preventive measures are in place for PTSD, making this discovery promising.
The researchers observed that chronic stress affects a critical brain structure for fear generation, the amygdala. During stress, the amygdala produces higher levels of growth hormone, a response unique to this brain region. The researchers found that ghrelin, primarily produced in the stomach and present throughout the body, controls the release of growth hormone in the amygdala.
In experiments with rats, they discovered that stimulating the ghrelin receptor or overexpressing growth hormone over extended periods heightened the rats’ fear response. These rats showed increased fear compared to normal rats, as measured by their freezing behavior when exposed to a fearful tone. Blocking the cell receptors that interact with ghrelin or growth hormone reduced fear levels in chronically stressed rats.
The Link with PTSD
Notably, ghrelin and amygdalar growth hormone levels increased in rats exposed to chronic stress, leading to stronger encoding of fearful memories. The researchers believe similar processes might occur in people who suffer from PTSD. The history of stress alters an individual’s biology, leading to excessively strong memories of traumatic events and driving PTSD symptoms.
This groundbreaking study highlights how ghrelin and growth hormone affect the amygdala’s output, impacting affective symptoms of stress-related psychiatric disorders. The discovery presents new opportunities for developing therapeutic strategies against stress-induced fear.
The researchers believe that existing drug compounds that interfere with ghrelin could be repurposed for stress therapies. These compounds have been deemed safe for human use, and they could potentially serve as preventive measures or treatments for PTSD. The researchers are applying for a patent for using anti-ghrelin treatments to address stress-exacerbated psychiatric disorders.
PTSD affects millions of Americans, including soldiers and victims of various traumatic events. While some patients recover within five years, a significant percentage never fully recover. The researchers hypothesize that persistent elevation of ghrelin following trauma exposure might be a contributing factor to maintaining PTSD. By targeting ghrelin, it may be possible to dampen its effects and potentially reverse PTSD with the aid of cognitive behavioral therapy over time.
The research team plans to study ghrelin levels in human patients with anxiety and fear disorders and conduct a clinical trial using a drug that blocks ghrelin to prevent depression relapse in collaboration with Massachusetts General Hospital.
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