A new study has revealed that the body’s hormone stress response is why some people develop post-traumatic stress disorder following trauma exposure, and others don’t. The finding could lead to more targeted treatments for the condition.
Some people develop post-traumatic stress disorder (PTSD) following exposure to a traumatic event or events, causing notable impairments such as intrusive thoughts, avoiding behaviors, sleep disturbance and hypervigilance.
Crucial to identifying the condition early, and treating it effectively, is understanding why some people, and not others, develop PTSD. Now, a new study by researchers at the Swiss Federal Institute of Technology Lausanne (EPFL) has shown why a subset of people are more vulnerable, and it has to do with the body’s stress hormone response.
“There are considerable differences in the levels of glucocorticoids that individuals release to the bloodstream when stressed,” said Carmen Sandi, one of the study’s corresponding authors. “Low glucocorticoid levels are frequently observed in PTSD patients following trauma exposure and were initially suspected to be a consequence of trauma exposure.”
Glucocorticoids are steroid hormones produced by the adrenal glands, which sit atop each kidney. The essential glucocorticoid the body produces is cortisol, the primary stress hormone that works with certain parts of the brain to control mood, motivation, and fear. Following the fight-or-flight response, if the brain continues to perceive something as dangerous, it triggers a pathway that results in the release of cortisol.
While low glucocorticoid levels and a smaller hippocampus, the area of the brain involved in long-term memory formation and memory retrieval, were originally thought to result from trauma, they’re currently viewed as potential risk factors for PTSD. However, establishing their causal role in the condition has proven difficult.
“The possibility that this could be a trait constituting a preexisting PTSD risk factor has been an outstanding open question for many years, but tackling it has been challenging due to the difficulties of both collecting biological measures before trauma exposure and having access to relevant animal models in which the causal role of these traits can be investigated," said Sandi.
To examine how a reduced hormonal response to stress might be linked to PTSD symptoms, the researchers used rats that had been genetically modified to mimic humans with a blunted response to cortisol. They measured the volume of different brain regions, trained rats to associate a cue with fear, recorded their sleep patterns, and measured their brain activity.
The researchers discovered that decreased responsiveness to glucocorticoids led to several pivotal PTSD vulnerability traits, including impaired fear extinction (in male rats), reduced hippocampal volume, and rapid-eye-movement sleep (REMS) disturbances. Fear extinction is a process by which a conditioned fear response diminishes over time; problems with fear extinction mark PTSD. REMS is crucial for memory consolidation, and people with PTSD often experience REMS disturbances. From this, the researchers concluded these traits are biologically interconnected and not independent risk factors.
Next, the rats were given the equivalent of cognitive behavioral therapy to reduce their learned fears and then administered corticosterone, the murine version of cortisol. The researchers noted that both excessive fear and REM sleep disturbances abated. In addition, increased levels of the fight-or-flight neurotransmitter norepinephrine in the brain returned to normal.
“Our study provides causal evidence of a direct implication of low glucocorticoid responsiveness in the development of PTSD symptomatology following exposure to traumatic experiences, i.e., impaired fear extinction,” Sandi said. “In addition, it shows that low glucocorticoids are causally implicated in the determination of other risk factors and symptoms that were until now only independently related to PTSD.”
The study’s findings open the door to potential treatment for people with PTSD.
“Our research illuminates previously elusive aspects of PTSD, revealing that blunted corticosteroid responsiveness not only predicts but may also contribute causally to core PTSD symptoms,” the researchers said. “This suggests potential benefits of glucocorticoid treatments for patients with diminished glucocorticoid responsiveness.”
The study was published in the journal Biological Psychiatry.
Source: EPFL
