In an experimental study published in Translational psychiatry, taking a single dose of hydrocortisone immediately after watching a stressful movie reduced intrusive memories related to the movie compared to the placebo group in the following days. Voluntary memory was not affected. The effect was seen in both men and women.
Persistent and distressing involuntary memories are a feature of many psychological disorders. In post-traumatic stress disorder or PTSD, they are one of the most prominent features. PTSD develops as a result of experiences of psychological trauma and is found in trauma survivors worldwide. Contrary to its wide distribution, processing capabilities are lacking.
Researchers are investigating ways to prevent the development of PTSD and one of the promising approaches focuses on preventing the consolidation of traumatic memory. Conceptually, if a disorder is primarily characterized by intrusive memories, preventing the formation of such memories could potentially prevent the disorder as a whole. But can we prevent the formation of these memories by using ingestible drugs?
“Only among psychiatric disorders is there a known cause of PTSD,” explained study author Sunjeev Kamboj, professor of translational clinical psychology at University College London. “The cause is usually a traumatic (often life-threatening) event, which triggers a cascade of biological events in the brain that ultimately lead to symptoms of PTSD, including the so-called ‘re-experience’ symptom cluster ‘ which includes involuntary memories, and in extreme cases, actual flashbacks.
“These arise because the biochemical processes involved in ordinary memory formation are ‘hijacked’ by the traumatic event, resulting in abnormally strong memories. This abnormal reinforcement occurs within hours or days of the traumatic event. event, and therefore we have a window of opportunity after a traumatic event to interfere with the formation of traumatic memories.
“For example, it might be possible to use drugs to interrupt the biochemical processes involved in the formation of hyper-strong trauma memories,” Kamboj explained. “Various lines of experimental and clinical evidence suggest that elevated levels of cortisol, the ‘stress hormone’, may be associated with a reduction in the onset of PTSD. My lab is particularly interested in the development of treatments that affect the memory formation, so we wanted to know if giving participants cortisol (in the form of an oral drug, “hydrocortisone”) immediately after a simulated mild traumatic event in the laboratory, would affect the occurrence of traumatic memories later.
“We were also very interested in the role of sex and sex hormones in PTSD, so we also looked at whether the effects of hydrocortisone would be affected by background levels of estrogen and progesterone. Incidentally, it is important to remember that both women and men have these “female” sex hormones in their systems! »
To test this, Kamboj and his colleagues conducted an experimental study on 120 healthy young adult volunteers, ages 18 to 35, recruited through online advertisements. The participants were randomly divided into two groups – an experimental group and a placebo group.
All participants had their blood pressure and heart rate measured and saliva samples taken before and after the experiment. They performed a set of psychological assessments of mental health and general psychological characteristics that included depression (Beck Depression Inventory), anxiety (Spielberger Trait Anxiety Inventory), dissociation (Dissociative Experiences Scale-II), quality sleep and more.
Before and after the experimental treatment, the researchers assessed subjective affect (Positive and Negative Affect Schedule, PABAS) and a range of subjective cognitive and physical sensations (The Bodily Symptoms Scale).
The experiment took place over 8 days. On the first day, after completing the psychological and medical assessments described, all participants viewed a stressful film, intended to portray a traumatic experience. After the movie was finished, the experimenters administered capsules containing 30 mg of hydrocortisone to the experimental group and identical-looking capsules without active agents (placebo) to the control group.
The experiment followed a double-blind procedure, which means that neither the experimenters, the people who gave capsules and conducted the experiment, nor the study participants knew whether they were part of the experimental group or the control group, i.e. whether they took a hydrocortisone or a placebo capsule.
A 2-hour period followed to allow the drug to be absorbed, and participants were instructed to press a button on a wrist-worn device given to them whenever they had an intrusive memory related to the movie. For the next 6 days, participants were required to complete a memory journal in which they would record intrusive memories related to the film.
As expected, over time, intrusive movie-related memories became less frequent, but this reduction in frequency was more rapid in the group that ingested hydrocortisone capsules. While occurrences of intrusive memories were the same on average on day 1 in both groups, day 2 already, and every day after, intrusive memories about the movie were rarer in the group given hydrocortisone than in the placebo group.
However, the difference became large enough to be confirmed by statistical tests, only from the fourth day. Further analyzes confirmed the expectation that the frequency of intrusive memories decreased more rapidly over time in the hydrocortisone group.
“Although the results need to be properly tested in larger clinical trials with recently traumatized individuals, it appears that hydrocortisone may help people ‘forget’ traumatic events more quickly if given for a very short time. after a traumatic event,” Kamboj told PsyPost. “This is going to be difficult to test in a clinical setting because traumatized people are usually treated in chaotic and busy emergency departments, and often their physical needs naturally take precedence over mental health. ”
“Nevertheless, a team in New York is doing this difficult work in a large-scale clinical trial using a very high dose of hydrocortisone (6 times higher than the dose we used in our study). The researchers expect to have preliminary results in the spring or summer of 2023.”
The effects of hydrocortisone were the same for people of both sexes, but seemed to depend on levels of female sex hormones – estradiol and progesterone. “Men treated with hydrocortisone showed less intrusion as estradiol levels increased, whereas women showed the opposite pattern,” the authors conclude, noting that a similar effect of progesterone was also present, but less pronounced.
“Although hydrocortisone, on average, accelerated the rate at which people forgot the traumatic event, the total number of involuntary memories they had after hydrocortisone treatment seemed to depend on their estrogen levels. and circulating progesterone,” Kamboj said.
“And how these two hormones interacted with hydrocortisone seemed to differ in men and women. Overall, our results suggest that the usefulness (or even potential harm) of hydrocortisone depends on biological sex and gender. estrogen and progesterone levels in saliva For example, men with high estrogen levels had the fewest memories of unintended trauma after hydrocortisone.
“Interestingly, the women seemed to show the opposite pattern – higher estrogen levels in women were associated with more intrusive memories after hydrocortisone treatment,” the researcher continued. “Of course, these preliminary results need to be replicated, but they suggest that hydrocortisone may not be a universally beneficial treatment for the prevention of PTSD and we need to do more work to determine what factors are responsible for making hydrocortisone effective preventative treatment and whether there are any conditions that potentially make it a harmful treatment in some people.
The study makes an important contribution to the search for new ways to prevent the harmful psychological consequences of trauma. However, the authors note that the study design in which film is used to elicit intrusions may not “adequately reflect the phenomenon observed following actual trauma.”
“As noted above, the key question is whether hydrocortisone is effective in trauma victims,” Kamboj explained. “There is unlikely to be a simple answer to this question. For example, the clinical trial I mentioned tests a (very high) dose of hydrocortisone, but we know from a lot of previous experimental work that the effects of hydrocortisone are highly dose-dependent and that the relationship between the dose and the response is not linear. ”
“I hope these researchers selected ‘the right’ dose to test, but if they don’t find an effect of hydrocortisone on preventing PTSD, we won’t know if it’s because the dose n was not quite correct.”
The study, “Acceleration of Forgetting a Traumatic Event in Healthy Men and Women After a Single Dose of Hydrocortisone,” was authored by Vanessa E. Hennessy, Luzia Troebinger, Georges Iskandar, Ravi K Das and Sunjeev K. Kamboj.
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