Scientists find why only some people develop PTSD

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Posttraumatic stress disorder (PTSD) is a debilitating condition that affects individuals exposed to traumatic events, with about 25%–35% of them developing the disorder.

Researchers at the École Polytechnique Fédérale de Lausanne (EPFL) have conducted a groundbreaking study that sheds light on why only certain individuals are susceptible to PTSD.

This research focuses on the body’s response to stress hormones and offers potential avenues for more targeted PTSD treatments.

Unpacking the PTSD Puzzle

The development of PTSD has long been a subject of scientific inquiry, as understanding the factors that contribute to its onset is essential for prevention and treatment strategies.

One critical component in this puzzle is the role of glucocorticoids, stress hormones like cortisol, released by the body in response to stress.

Low levels of glucocorticoids have been observed in individuals with PTSD after trauma exposure, initially believed to be a consequence of the trauma itself.

However, it remained unclear whether these low hormone levels constituted a preexisting risk factor for PTSD.

The EPFL researchers aimed to investigate the connection between reduced hormonal stress responses and the development of PTSD.

Their study involved the use of a genetically selected rat model that mirrored individuals with blunted cortisol responses.

To explore this link further, the team employed a combination of methods, including MRI scans, fear conditioning experiments, sleep pattern analysis, and brain activity measurements.

Unraveling the Connections

Through their multifaceted approach, the researchers uncovered significant insights:

Fear Extinction Impairment: In male rats with reduced glucocorticoid responsiveness, fear extinction—the process by which conditioned fear responses diminish over time—was impaired. This impairment is a hallmark of PTSD.

Hippocampal Volume Reduction: Rats with blunted cortisol responses exhibited reduced hippocampal volume. The hippocampus is a critical brain region involved in memory processing and emotional regulation.

REM Sleep Disturbances: Disturbances in rapid-eye movement (REM) sleep patterns, essential for memory consolidation, were identified in these rats. Such disturbances have long been associated with PTSD in humans.

Intervention and Recovery

The study did not stop at identifying these connections. To validate their findings, the researchers treated the rats with cognitive and behavioral therapy to reduce learned fears and then administered corticosterone, a stress-related hormone. The results were promising:

Fear Reduction: Excessive fear and disturbances in REM sleep patterns receded in the treated rats.

Norepinephrine Normalization: Levels of the stress-related neurotransmitter norepinephrine in the brain returned to normal.

Causal Evidence

Principal Investigator Carmen Sandi emphasized the significance of their findings: “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.”

Furthermore, this research demonstrates that low glucocorticoids contribute causally to other PTSD risk factors and symptoms, previously studied independently.

Lead author Silvia Monari summarized, “In a nutshell, we present mechanistic evidence—previously missing—that having low glucocorticoids such as cortisol in humans is a condition for causally predisposed individuals to present all to-date vulnerability factors for developing PTSD, and causally involved in deficits to extinguish traumatic memories.”

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The research findings can be found in Biological Psychiatry.

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