- Traumatic memories are represented differently than sad memories in the brains of people with PTSD, research shows Medical Xpress
- Brain Study Suggests Traumatic Memories Are Processed as Present Experience The New York Times
- Brain Activity in PTSD: Trauma Memories Differ from Sad Ones Neuroscience News
- Neural patterns unravel distinctions between traumatic and sad memories in individuals with PTSD News-Medical.Net
- PTSD patients’ brains work differently when recalling traumatic experiences Popular Science
- View Full Coverage on Google News
Tag Archives: PTSD
Major Trial Finds MDMA-Assisted Therapy Is Effective for PTSD, Paving Way for FDA Approval – Gizmodo
- Major Trial Finds MDMA-Assisted Therapy Is Effective for PTSD, Paving Way for FDA Approval Gizmodo
- Psychedelic drug MDMA eases PTSD symptoms in a study that paves the way for possible US approval The Associated Press
- MDMA Therapy for PTSD Inches Closer to U.S. Approval The New York Times
- MDMA-Assisted Therapy Demonstrates Significant Reductions in Post-Traumatic Stress Disorder Symptoms in Phase 3 Study Pharmacy Times
- After Latest Clinical Trial, MDMA Therapy For PTSD Is ‘On Track’ For FDA Consideration Next Year Marijuana Moment
- View Full Coverage on Google News
Jennifer Lopez jokes she had ‘PTSD’ before Ben Affleck wedding
Jennifer Lopez experienced “a little PTSD” before marrying Ben Affleck.
Because the couple’s previous engagement “fell apart,” the singer kept asking herself whether their second attempt at tying the knot was “really happening,” she explained to Jimmy Kimmel Wednesday.
“We were so happy and, of course, it was happening, but the wedding was so stressful,” the Grammy winner, 53, recalled.
Lopez noted that their July 2022 Las Vegas wedding was Affleck’s idea.
“One day, Ben just said, ‘F–k it, let’s just go to Vegas and get married tonight,’” the dancer said. “He said, ‘Go to rehearsal. When you get back here, I’ll have everything set up.’”
One month after the pair tied the knot in Sin City, they went on to wed again in front of family and friends in Georgia.
Lopez and the Oscar winner, 50, were previously engaged from 2002 to 2004. The “Gigli” co-stars rekindled their romance in 2021.
By that time, the songwriter was fresh off a broken engagement from Alex Rodriguez. Lopez was previously married to Marc Antony, with whom she shares twins Emme and Maximilian, 14.
As for Affleck, the “Tender Bar” star wed Jennifer Garner in 2005. Prior to their 2015 split, the exes welcomed Violet, 17, Seraphina, 14, and Samuel, 10.
After Lopez and the actor got back together, Affleck proposed with a green diamond ring.
“He had to ask me again,” Lopez said on “Jimmy Kimmel Live!” of the April 2022 proposal, which took place while she was in the bathtub. “I didn’t have that [ring] anymore.”
Affleck gushed to Vogue about their second-chance romance in November 2022, calling Lopez “exactly the person” he remembers “from 20 years ago.”
The Golden Globe winner winner added, “Maybe she sees all the changes she’s made, whereas when I see her, mostly I just see someone who has retained, against the odds, the thing about her that always made her the most incredible to me.”
Blood Pressure Drug Holds Promise for Treating PTSD
Summary: Clonidine, an FDA-approved medication commonly prescribed to treat blood-pressure disorders and ADHD, shows promise in mitigating the effects of PTSD.
Source: Medical College of Georgia at Augusta University
There is new evidence that a 50-year-old blood pressure drug could find new purpose as a treatment to mitigate the often life-altering effects of increasingly prevalent PTSD, scientists say.
Clonidine is commonly used as a high blood pressure medication and for ADHD. It’s also already been studied in PTSD because clonidine works on adrenergic receptors in the brain, likely best known for their role in “fight or flight,” a heightened state of response that helps keep us safe. These receptors are thought to be activated in PTSD and to have a role in consolidating a traumatic memory.
Clonidine’s sister drug guanfacine, which also activates these receptors, also has been studied in PTSD. Conflicting results from the clinical trials have clonidine, which has shown promise in PTSD, put aside along with guanfacine, which has not.
Scientists at the Medical College of Georgia at Augusta University say it’s time for another look at clonidine.
They have laboratory evidence that while the two drugs bind to the same receptors, they do different things there, says Qin Wang, MD, Ph.D., neuropharmacologist and founding director of the Program for Alzheimer’s Therapeutics Discovery at MCG.
Their results published in the journal Molecular Psychiatry suggest that clonidine could provide immediate treatment to the significant number of people emerging from the current pandemic with PTSD, as well as from longer-established causes like wars and other violence.
Large-scale clinical trials of clonidine in PTSD are warranted, the scientists write. Their studies also indicate that other new therapies could be identified by looking at the impact on activation of a key protein called cofilin by existing drugs.
The new studies looked in genetically modified mice as well as neurons that came from human stem cells, which have the capacity to make many cell types.
In the hippocampus, the center of learning and memory, they found that a novel axis on an adrenergic receptor called ɑ2A is essential to maintaining fear memories in which you associate a place or situation, like the site of a horrific car accident or school shooting, with fear or other distressing emotions that are hallmarks of PTSD.
In this axis, they found the protein spinophilin interacts with cofilin, which is known to control protrusions on the synapses of neurons called dendritic spines, where memories are consolidated and stored.
A single neuron can have hundreds of these spines which change shape based on brain activity and whose changing impacts the strength of the synapse, the juncture between two neurons where they swap information.
“Normally whenever there is a stimulation, good or bad, in order to memorize it, you have to go through a process in which the spines store the information and get bigger,” Wang says, morphing from a slender profile to a more mushroom-like shape.
“The mushroom spine is very important for your memory formation,” says corresponding author Wang, Georgia Research Alliance Eminent Scholar in Neuropharmacology. For these mushroom shapes to happen, levels of cofilin must be significantly reduced in the synapse where the spines reside. That is where clonidine comes in.
The scientists found clonidine interferes with cofilin’s exit by encouraging it to interact with the receptor which consequently interferes with the dendritic spine’s ability to resume a mushroom shape and retain the memory. Guanfacine, on the other hand, had no effect on this key player cofilin.
The findings help clarify the disparate results in the clinical trials of these two similar drugs, Wang says. In fact, when mice got both drugs, the guanfacine appeared to lessen the impact of clonidine in the essential step of reconsolidating—and so sustaining—a traumatic memory, indicating their polar-opposite impact at least on this biological function, Wang says.
There was also living evidence. In their studies that mimicked how PTSD happens, mice were given a mild shock then treated with clonidine right after they were returned to the place where they received the shock and should be recalling what happened earlier.
Clonidine-treated mice had a significantly reduced response, like freezing in their tracks, compared to untreated mice when brought back to the scene. In fact, their response was more like the mice who were never shocked. Guanfacine had no effect on freezing behavior.
Obviously, Wang says, they cannot know for certain how much the mice remember of what previously happened, but clearly those treated with clonidine did not have the same overt reaction as untreated mice or those receiving guanfacine.
“The interpretation is that they don’t have as strong a memory,” she says, noting that the goal is not to erase memories like those of wartime, rather diminish their disruption in a soldier’s life.
When a memory is recalled, like when you return to an intersection where you were involved in a horrific car wreck, the synapses that hold the memory of what happened there become temporarily unstable, or labile, before the memory restabilizes, or reconsolidates. This natural dynamic provides an opportunity to intervene in reconsolidation and so at least diminish the strength of a bad memory, Wang says. Clonidine appears to be one way to do that.
Adrenergic drugs like clonidine bind to receptors in the central nervous system to reduce blood levels of the stress hormones you produce like epinephrine (adrenaline) and norepinephrine, which do things like increase blood pressure and heart rate.
Studies like one that came out 15 years ago, which only looked at guanfacine, indicated it was of no benefit in PTSD. But then in 2021, a retrospective look at a cohort of 79 veterans with PTSD treated with clonidine, for example, indicated 72% experienced improvement and 49% were much improved or very much improved with minimal side effects.
Previous basic science studies also have indicated that manipulating the adrenergic receptor can impact fear memory formation and memory, but how has remained unknown.
PTSD has emerged as a major neuropsychiatric component of the COVID-19 pandemic, affecting about 30% of survivors, a similar percentage of the health care workers who care for them and an estimated 20% of the total population, Wang says, which means the impact on human health and health care systems could be “profound.”
Psychotherapy is generally considered the most effective treatment for PTSD, and some medications, like antidepressants, can also be used, but there are limited drug options, which include only two drugs which have Food and Drug Administration approval specifically for the condition, she says. The lack of approved drugs has led to off-label uses of drugs like clonidine.
See also
Cofilin is a key element in helping muscle cells and other cell types contract as well as the flexibility of the cytoskeleton of the dendritic spine. A single neuron can have thousands of dendritic spines which change shape based on brain activity and whose changing shape impacts the strength of the synapse.
The U.S. Department of Veterans Affairs defines post-traumatic stress disorder as a mental health problem that some people develop after experiencing or witnessing a life-threatening or traumatic event.
While problems like feeling on edge, trouble sleeping and/or nightmares may last a few weeks or more after the event, if symptoms like these as well as flashbacks and increasingly negative thoughts continue, it’s likely PTSD. Sometimes symptoms don’t surface until months after the initial event.
About this PTSD and psychopharmacology research news
Author: Press Office
Source: Medical College of Georgia at Augusta University
Contact: Press Office – Medical College of Georgia at Augusta University
Image: The image is in the public domain
Original Research: Open access.
“Activation of a novel α2AAR-spinophilin-cofilin axis determines the effect of α2 adrenergic drugs on fear memory reconsolidation” by Shalini Saggu et al. Molecular Psychiatry
Abstract
Activation of a novel α2AAR-spinophilin-cofilin axis determines the effect of α2 adrenergic drugs on fear memory consolidation
Posttraumatic stress disorder (PTSD) after the pandemic has emerged as a major neuropsychiatric component of post-acute COVID-19 syndrome, yet the current pharmacotherapy for PTSD is limited.
The use of adrenergic drugs to treat PTSD has been suggested; however, it is hindered by conflicting clinical results and a lack of mechanistic understanding of drug actions.
Our studies, using both genetically modified mice and human induced pluripotent stem cell-derived neurons, reveal a novel α2A adrenergic receptor (α2AAR)-spinophilin-cofilin axis in the hippocampus that is critical for regulation of contextual fear memory consolidation.
In addition, we have found that two α2 ligands, clonidine and guanfacine, exhibit differential abilities in activating this signaling axis to disrupt fear memory consolidation.
Stimulation of α2AAR with clonidine, but not guanfacine, promotes the interaction of the actin binding protein cofilin with the receptor and with the dendritic spine scaffolding protein spinophilin to induce cofilin activation at the synapse. Spinophilin-dependent regulation of cofilin is required for clonidine-induced disruption of contextual fear memory consolidation.
Our results inform the interpretation of differential clinical observations of these two drugs on PTSD and suggest that clonidine could provide immediate treatment for PTSD symptoms related to the current pandemic. Furthermore, our study indicates that modulation of dendritic spine morphology may represent an effective strategy for the development of new pharmacotherapies for PTSD.
Head Trauma and PTSD May Increase Genetic Variant’s Impact on Alzheimer’s Risk
Summary: The risk of developing Alzheimer’s disease and dementia-related symptoms is higher in those with TBI and PTSD who carry the APOE E4 gene.
Source: Veterans Affairs Research Communications
In a study of Veterans led by Dr. Mark Logue, a statistician in the National Center for PTSD at the VA Boston Healthcare System, researchers concluded that PTSD, TBI, and the ε4 variant of the APOE gene show strong associations with Alzheimer’s disease and related dementias (ADRD).
The medical community has never researched the simultaneous impact of post-traumatic stress disorder (PTSD), traumatic brain injury (TBI) and genetic risk factors in a large cohort until now. They first found a greater percentage of ADRD in Veterans with PTSD and in those with TBI, relative to those without, as well as higher rates of ADRD in Veterans who had inherited the ε4 variant. Logue and his team then looked for interactions between the ε4 variant, PTSD, and TBI using a mathematical model.
The study found an increase in risk due to PTSD and TBI in Veterans of European ancestry who inherited the ε4 variant. In Veterans of African ancestry, the impact of PTSD didn’t vary as a function of ε4, but the TBI effect and interaction with ε4 was even stronger. Other studies have suggested that ε4 may magnify the effects of a head injury and/or combat-related stress.
“These additive interactions indicate that ADRD prevalence associated with PTSD and TBI increased with the number of inherited APOE ε4 alleles,” Logue and his colleagues wrote. “PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and doing accurate ADRD risk assessment.”
Capitalizing on VA’s Million Veteran Program
The researchers carried out the study by accessing data from VA’s Million Veteran Program (MVP), one of the world’s largest databases of health and genetic information. MVP is aimed at learning how genes, lifestyle, and military exposures affect health and illness, with more than 900,000 Veterans enrolled in its climb to 1 million and beyond.
With more than 40% of the Veteran population above the age of 75, the number of former Service Members at risk for Alzheimer’s and other forms of dementia is rising. While large cohort studies have shown that PTSD and TBI increase the risk of dementia in Veterans, Logue and his colleagues investigated further by studying these risk factors along with the APOE ε4 variant. Most people don’t inherit that variant, but those who do inherit it from one parent (one copy) or both of their parents (two copies).
“Research has shown that if you inherit one copy of ε4, you’re at increased risk of Alzheimer’s disease,” he said, “and if you inherit two copies, you are at much higher risk.”
The number of ε4 variants a person inherits is fixed at birth, but their impact differs with age, according to Logue, who is also an Army Veteran and an associate professor at Boston University.
“The risk of Alzheimer’s disease increases with age for all of the APOE genotypes,” he said. “But when compared to people with two copies of the common variant, the difference in risk for those with a copy of ε4 appears to peak somewhere between age 65 and 70 and then decrease after that. Again, that doesn’t mean that your chances of Alzheimer’s decrease after that, just that the difference between the risk for those with and without ε4 diminishes.”
The study showed that the risk associated with PTSD and head injury was larger for ε4 carriers. Their model led the researchers to expect that for 80-year-old Veterans of European ancestry who didn’t inherit the ε4 variant, the percentage of ADRD would be 6% greater for those with PTSD compared to those without. But for 80-year-old Veterans of European ancestry who inherited two copies of ε4, the percentage of ADRD would be 11% higher for those with PTSD than those without.
Clear link between PTSD, TBI on dementia risk a surprise
Logue was most surprised to see such clear evidence of a link between PTSD and head trauma on dementia risk.
“I’ve worked in Alzheimer’s disease genetics for over a decade now, and I was used to seeing a clear impact of APOE ε4 on Alzheimer’s risk,” he says. “However, in this cohort, the effects of PTSD and head injury were just as clear and looked similar to the effect of inheriting ε4 from one of your parents.”
Next, Logue and his colleagues would like to use MVP data to research other risk factors that are relevant to Veterans, with the goal of learning how they may interact with Alzheimer’s risk variants. They are also looking to do genome-wide association scans to try to find new Alzheimer’s and dementia risk variants. The most recent large-scale genome-wide association study of Alzheimer’s identified some 80 variants linked to the risk of Alzheimer’s, Logue said, noting that those variants were rare or had a much smaller impact than ε4.
MVP data can be used to boost power for this type of study, he added, but PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and conducting accurate ADRD risk assessments.
“We know that genes play a large role in Alzheimer’s risk, but they don’t tell the whole story,” Logue explained.
“Right now, no genetic test can tell you if you’re certain to develop Alzheimer’s disease. Tests can only give an estimate of your likelihood of developing Alzheimer’s that may be higher or lower than average. Our study shows that these estimates will be more accurate if they incorporate more than just age and genetics.
See also
“In Veterans, a history of head injuries and PTSD can also make a large difference in dementia risk, so using that information will allow for more accurate measurement of the chances of developing dementia.”
About this neurology research news
Author: Mike Richman
Source: Veterans Affairs Research Communications
Contact: Mike Richman – Veterans Affairs Research Communications
Image: The image is in the public domain
Original Research: Open access.
“Alzheimer’s disease and related dementias among aging veterans: Examining gene‐by‐environment interactions with post‐traumatic stress disorder and traumatic brain injury” by Mark W. Logue et al et al. Alzheimer’s & Dementia
Abstract
Alzheimer’s disease and related dementias among aging veterans: Examining gene‐by‐environment interactions with post‐traumatic stress disorder and traumatic brain injury
Introduction
Post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) confer risk for Alzheimer’s disease and related dementias (ADRD).
Methods
This study from the Million Veteran Program (MVP) evaluated the impact of apolipoprotein E (APOE) ε4, PTSD, and TBI on ADRD prevalence in veteran cohorts of European ancestry (EA; n = 11,112 ADRD cases, 170,361 controls) and African ancestry (AA; n = 1443 ADRD cases, 16,191 controls). Additive-scale interactions were estimated using the relative excess risk due to interaction (RERI) statistic.
Results
PTSD, TBI, and APOE ε4 showed strong main-effect associations with ADRD. RERI analysis revealed significant additive APOE ε4 interactions with PTSD and TBI in the EA cohort and TBI in the AA cohort. These additive interactions indicate that ADRD prevalence associated with PTSD and TBI increased with the number of inherited APOE ε4 alleles.
Discussion
PTSD and TBI history will be an important part of interpreting the results of ADRD genetic testing and doing accurate ADRD risk assessment.
MDMA could be approved in the US in MONTHS: Rave drug ‘statistically significant’ in treating PTSD
MDMA could be available in US hospitals in 2024 after showing promise as a powerful treatment for PTSD.
Researchers behind a landmark, federally-funded trial told DailyMail.com they expect to submit a new drug application within months.
The US Food and Drug Administration will make a decision on approval possibly as soon as six months later.
The move could see MDMA offered to some of the 12 million American adults who suffer with post traumatic stress disorder (PTSD).
Also known as ecstasy or molly, the drug is popular in rave culture, where it is used to dance all night long and feel more connected to the music and other ravers.
But it has become part of a new frontier of psychedelics that are being repurposed as drugs for trauma and depression, along with ketamine, magic mushrooms and LSD.
A trial of 90 patients with severe PTSD in 2021 showed that 88 per cent went into remission after taking the drug accompanied by therapy.
The second phase 3 trial of MDMA therapy for PTSD in the US was completed this month, testing the drug on patients whose PTSD is not as severe, as well as on more people of color. Data from the trial is yet to be released.
The Multidisciplinary Association for Psychedelic Studies (MAPS) — a nonprofit organization raising awareness of psychedelics — is running the trials.
Patients take a standard dose of the drug while under supervision. Sessions with a therapist then help people to come to terms with their trauma
Clinical trial participants were given 80 mg or 120 mg of MDMA — the standard amount for a pill — plus a supplementary dose of 40-60mg
A spokesperson told DailyMail.com: ‘We anticipate filing our NDA in the third quarter of 2023 [July to September].
‘Based on that estimated filing date we anticipate a possible approval in the second quarter of 2024 [April to June] and launch in the fourth quarter of 2024 [October to December].’
The latest study was completed ahead of schedule, meaning a New Drug Application could be submitted to the FDA by mid-2023.
The FDA’s review teams could take just six months to approve the drug, meaning it could be approved as early as April 2024 and rolled out in the autumn.
The drug is likely to be given in a clinic, similar to how the trials were conducted.
Participants were given 80 mg or 120 mg of MDMA — which is roughly the amount in the average ecstasy pill sold on the street.
Patients wore headphones and an eye mask, with a researchers who sat with them for eight hours to oversee their reaction. They were then given a booster dose of 40-60mg about two hours into the session.
The next morning, they had a 90-minute session with a therapist who helped them talk about, and process, their experience.
Results showed 67 per cent of participants no longer qualified for a PTSD diagnosis after just three MDMA therapy sessions. In total, 88 per cent of people had significant improvements in their symptoms.
Current treatments for PTSD include harsh antidepressants which suppress the immune system and cause a range of side effects, as well as some talking therapies.
While these drugs can help, they are not very effective in patients with severe PTSD, and the results fade over time.
MDA is thought to rewire connections in the brain, dampening the part that makes people scared, allowing them to open up with a therapist and face their trauma head on, instead of burying it.
The psychedelic also quietens the amygdala — the fear center in the brain — so that people can rationalize their trauma and comprehend that they survived it.
Some 90 patients took part in the first phase 3 trial, and were randomly assigned to receive MDMA assisted therapy or a placebo, along with 12 therapy sessions.
A letter in May from the US Department of Health and Human Services reinforced the FDA’s ‘anticipated approval’ of psychedelic therapies ‘within approximately 24 months’.
PTSD can occur after a distressing event, and can cause flashbacks, nightmares and intense anxiety.
The disorder affects 12 million adults in the US every year, and roughly six per cent of the population will have it at some point in their life.
A study in March this year by the University of California found that giving MDMA to people with PTSD doubled their chance of getting better through counselling.
Two thirds of PTSD sufferers given a 40mg dose of the party drug before therapy no longer suffered with the condition after two months.
By contrast, one in three of the control group who received standard counselling alone were cured over the same period of time.
The MDMA combination even worked on patients with the most severe PTSD and those with drug and alcohol abuse problems, experts said.
Researchers said the ‘feelings of trust and closeness’ caused by the drug helped them open up to psychiatrists and make better progress.
If MDMA therapy is rolled out, it could open the floodgates for more psychedelics pitched for approval.
Psilocybin, LSD and ayahuasca are all being tested in clinical trials.
Taking hydrocortisone immediately after a traumatic event may help prevent PTSD
In an experimental study published in Translational Psychiatry, taking a single dose of hydrocortisone immediately after watching a stressful movie was found to reduce intrusive memories related to the movie compared to the placebo group in the following days. Voluntary memory was unaffected. The effect was observed in both men and women.
Persistent, distressing involuntary memories are a feature of many psychological disorders. In posttraumatic stress disorder or PTSD, they are one of the most prominent features. PTSD develops in the aftermath of experiences of psychological trauma and is found in trauma survivors worldwide. In contrast to its wide spread, capacities for treating it are lacking.
Researchers have been studying ways to prevent the development of PTSD and one of the promising approaches focuses on prevention of the consolidation of traumatic memory. Conceptually, if a disorder is primarily characterized by intrusive memories, preventing such memories from being formed could potentially prevent the disorder as a whole. But can the formation of these memories be prevented using ingestible drugs?
“Uniquely among psychiatric disorders, there is a known cause for PTSD,” explained study author Sunjeev Kamboj, a professor of translational clinical psychology at University College London. “The cause is usually a traumatic (often life-threatening) event, which sets off a cascade of biological events in the brain that eventually lead to symptoms of PTSD, including the so-called ‘re-experiencing’ cluster of symptoms that includes distressing involuntary memories, and in extreme cases, true 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 strengthening occurs in the hours or days after the event, and as a result, 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 raised levels of the ‘stress hormone’ cortisol might be associated with reduced occurrence of PTSD. My lab is particularly interested in developing treatments that affect memory formation, so we wanted to know whether giving participants cortisol (in the form of the oral medication, ‘hydrocortisone’) immediately after a mild simulated traumatic event in the lab, would affect the occurrence of subsequent traumatic memories.”
“We’ve also been 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 the background levels of estrogen and progesterone. Incidentally, it’s important to remember that 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, 18-35 years of age, recruited via online advertisements. Participants were randomly divided into two groups – an experimental and a placebo group.
All participants had their blood pressure and heart rate measured and saliva samples taken before and after the experiment. They completed 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), sleep quality and others.
Before and after the experimental treatment, 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 was conducted over 8 days. On the first day, after completing the described psychological and medical assessments, all participants viewed a stressful movie, intended as a proxy for traumatic experience. When the movie was finished, 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, meaning that neither the experimenters, people who were giving capsules and running the experiment, nor the study participants knew whether they were in the experimental or the control group i.e., whether they are taking a hydrocortisone or a placebo capsule.
A 2-hour period followed to allow for drug absorption and participants were tasked to press a button on a wrist-worn device issued to them whenever they had a movie-related intrusive memory. For the next 6 days, participants were to complete a memory diary in which they would record intrusive memories related to the movie.
As expected, with days passing, intrusive memories related to the movie became less frequent, but this reduction in frequency was faster in the group that ingested hydrocortisone capsules. While the occurrences of intrusive memories were the same on average on the first day in both groups, on the second day already, and all subsequent days, intrusive memories about the movie were rarer in the group that received hydrocortisone than in the placebo group.
However, the difference became large enough to be confirmed with statistical tests, only from the fourth day onward. Further analyses confirmed the expectation that the frequency of intrusive memories was declining faster with time in the hydrocortisone group.
“Although the findings need to be properly tested in larger scale clinical trials with recently traumatized individuals, it seems that hydrocortisone might help people to more quickly ‘forget’ traumatic events if it is given very soon after a traumatic event,” Kamboj told PsyPost. “This is going to be difficult to test in clinical settings because traumatized individuals are usually treated in busy, chaotic emergency departments, and often their physical needs understandably take precedence over mental health. ”
“Nonetheless, a team in New York is doing this challenging 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 spring or summer 2023.”
Effects of hydrocortisone were the same for people of both sexes, but appeared to depend on levels of female sex hormones – estradiol and progesterone. “Hydrocortisone-treated men showed fewer intrusions 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, sped up the rate at which people forgot about the traumatic event, the total number of involuntary memories they had after hydrocortisone treatment seemed to depend on their levels of circulating estrogen and progesterone,” Kamboj said.
“And the way in which these two hormones interacted with hydrocortisone seemed to differ in men and women. Overall, our findings suggested that whether hydrocortisone was helpful (or even potentially harmful) depended on biological sex, and the levels of estrogen and progesterone in saliva. For example, men with high levels of estrogen had the fewest involuntary trauma memories following hydrocortisone.”
“Interestingly, women seemed to show the opposite pattern – high levels of estrogen in women were associated with more intrusive memories following treatment with hydrocortisone,” the researcher continued. “Of course, these preliminary findings need to be replicated, but they suggest that hydrocortisone might not be a universally beneficial treatment for the prevention of PTSD and we need to do more work on determining which factors are responsible for making hydrocortisone an effective preventative treatment and whether there are conditions that potentially make it a harmful treatment in some individuals.”
The study provides an important contribution to finding new ways of preventing adverse psychological consequences of trauma. However, the authors note that the study design in which a movie is used to elicit intrusions might not adequately “mirror the phenomenon seen following real-life traumas.”
“As noted above, the key question is whether hydrocortisone is effective in trauma victims,” Kamboj explained. “There is unlikely to a simple answer to this question. For example, the clinical trial I mentioned is testing one (very high) dose of hydrocortisone but we know from a lot of previous experimental work that the effects of hydrocortisone strongly depend on its dose and that the relationship between dose and response is not linear.”
“I hope those researchers have selected ‘the right’ dose to test, but if they do not find an effect of hydrocortisone on PTSD prevention, we won’t know whether it was because the dose wasn’t quite right.”
The study, “Accelerated forgetting of a trauma-like 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.
for(var key in aepc_pixel_args) args[key] = aepc_pixel_args[key];
return args; };
// Extend args if ( 'yes' === aepc_pixel.enable_advanced_events ) { aepc_pixel_args.userAgent = navigator.userAgent; aepc_pixel_args.language = navigator.language;
if ( document.referrer.indexOf( document.domain ) < 0 ) {
aepc_pixel_args.referrer = document.referrer;
}
}
!function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function(){n.callMethod?
n.callMethod.apply(n,arguments):n.queue.push(arguments)};if(!f._fbq)f._fbq=n;
n.push=n;n.loaded=!0;n.version='2.0';n.agent="dvpixelcaffeinewordpress";n.queue=[];t=b.createElement(e);t.async=!0;
t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window,
document,'script','https://connect.facebook.net/en_US/fbevents.js');
fbq('init', aepc_pixel.pixel_id, aepc_pixel.user);
setTimeout( function() {
fbq('track', "PageView", aepc_pixel_args);
}, aepc_pixel.fire_delay * 1000 );
Read original article here
How Neurons From PTSD Patients React to Stress
Summary: Neurons derived from stem cells of combat veterans with PTSD react differently to stress hormones than those derived from veterans without PTSD. The findings shed new light on how genetics can cause some to develop PTSD following a traumatic event.
Source: Mount Sinai Hospital
Stem cell-derived neurons from combat veterans with post-traumatic stress disorder (PTSD) react differently to a stress hormone than those from veterans without PTSD, a finding that could provide insights into how genetics can make someone more susceptible to developing PTSD following trauma exposure.
The study, published October 20 in Nature Neuroscience, is the first to use induced pluripotent stem cell models to study PTSD. It was conducted by a team of scientists from the Icahn School of Medicine at Mount Sinai, the James J. Peters Veterans Affairs Medical Center, the Yale School of Medicine and The New York Stem Cell Foundation Research Institute (NYSCF).
Post-traumatic stress disorder can develop following severe trauma and is an enormous public health problem for both veterans and civilians. However, the extent to which genetic and environmental factors contribute to individual clinical outcomes remains unknown.
To bridge this information gap, the research team studied a cohort of 39 combat veterans with and without PTSD who were recruited from the James J Peters Veterans Affairs Medical Center in the Bronx. Veterans underwent skin biopsies and their skin cells were reprogrammed into induced pluripotent stem cells.
“Reprogramming cells into induced pluripotent stem cells is like virtually taking cells back in time to when they were embryonic and had the ability to generate all the cells of the body,” said Rachel Yehuda, Ph.D., Professor of Psychiatry, and Neuroscience, at Icahn Mount Sinai, Director of Mental Health for the James J. Peters Veterans Affairs Medical Center, and senior author of the paper.
“These cells can then be differentiated into neurons with the same properties as that person’s brain cells had before trauma occurred to change the way they function. The gene expression networks from these neurons reflect early gene activity resulting from genetic and very early developmental contributions, so they are a reflection of the ‘pre-combat’ or ‘pre-trauma’ gene expression state.”
“Two people can experience the same trauma, but they won’t necessarily both develop PTSD,” explained Kristen Brennand, Ph.D., Elizabeth Mears and House Jameson Professor of Psychiatry at Yale School of Medicine and a NYSCF—Robertson Stem Cell Investigator Alumna, who co-led the study.
“This type of modeling in brain cells from people with and without PTSD helps explain how genetics can make someone more susceptible to PTSD.”
To mimic the stress response that triggers PTSD, the scientists exposed the induced pluripotent stem cell-derived neurons to the stress hormone hydrocortisone, a synthetic version of the body’s own cortisol that is used as part of the “fight-or-flight” response.
“The addition of stress hormones to these cells simulates biological effects of combat, which allows us to determine how different gene networks mobilize in response to stress exposure in brain cells,” explained Dr. Yehuda.
Using gene expression profiling and imaging, the scientists found that neurons from individuals with PTSD were hypersensitive to this pharmacological trigger. The scientists also were able to identify the specific gene networks that responded differently following exposure to the stress hormones.
Inside the cells of PTSD-affected individuals
Most similar studies of PTSD to date have used blood samples from patients, but since PTSD is rooted in the brain, scientists need a way to capture how the neurons of individuals prone to the disorder are affected by stress. Therefore, the team opted to use stem cells, as they are uniquely equipped to provide a patient-specific, non-invasive window into the brain.
“You can’t easily reach into a living person’s brain and pull out cells, so stem cells are our best way to examine how neurons are behaving in a patient,” said Dr. Brennand.
NYSCF scientists used their scalable, automated, robotic system—The NYSCF Global Stem Cell Array—to create stem cells and then glutamatergic neurons from patients with PTSD. Glutamatergic neurons help the brain send excitatory signals and have previously been implicated in PTSD.
“As this was the first study using stem cell models of PTSD, it was important to study a large number of individuals,” said Daniel Paull, Ph.D., NYSCF Senior Vice President, Discovery & Platform Development, who co-led the study.
“At the scale of this study, automation is essential. With the Array, we can make standardized cells that allow for meaningful comparisons between numerous individuals, pointing to key differences that could be critical for discovering new treatments.”
Leveraging the hallmarks of stressed PTSD cells for new treatments
The team’s gene expression analysis revealed a set of genes that were particularly active in PTSD-prone neurons following their exposure to stress hormones.
“Importantly, the gene signature we found in the neurons was also apparent in brain samples from deceased individuals with PTSD, which tells us that stem cell models are providing a pretty accurate reflection of what happens in the brains of living patients,” noted Dr. Paull.
Moreover, the distinctions between how PTSD and non-PTSD cells responded to stress could be informative in predicting which individuals are at higher risk for PTSD.
“What’s really exciting about our findings is the opportunities they offer for accelerating the diagnosis and treatment of PTSD,” Dr. Paull continued.
“Importantly, having a robust stem cell model provides an ideal avenue to drug screening ‘in the dish,” even across diverse patient populations.”
“We’re working on finding already-approved drugs that could reverse the hypersensitivity we’re seeing in neurons,” added Dr. Brennand.
See also
“That way, any drugs we discover will have the fastest possible path to helping patients.”
The researchers plan to continue leveraging their induced pluripotent stem cell models to further investigate the genetic risk factors pinpointed by this study and to study how PTSD affects other types of brain cells, helping to broaden opportunities for therapeutic discovery.
“NYSCF is incredibly proud to have generated the first-ever induced pluripotent stem cell models from individuals with PTSD as part of this landmark study in partnership with world-class scientists,” said NYSCF Interim CEO Derrick Rossi, Ph.D.
“This collaborative work underscores the unique value of stem cell modeling for studying and demystifying challenging diseases, and for discovering innovative strategies that could lead to urgently needed treatments.”
About this genetics and PTSD research news
Author: Press Office
Source: Mount Sinai Hospital
Contact: Press Office – Mount Sinai Hospital
Image: The image is in the public domain
Original Research: Open access.
“Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression” by Daniel Paull et al. Nature Neuroscience
Abstract
Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression
Post-traumatic stress disorder (PTSD) can develop following severe trauma, but the extent to which genetic and environmental risk factors contribute to individual clinical outcomes is unknown.
Here, we compared transcriptional responses to hydrocortisone exposure in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons and peripheral blood mononuclear cells (PBMCs) from combat veterans with PTSD (n = 19 hiPSC and n = 20 PBMC donors) and controls (n = 20 hiPSC and n = 20 PBMC donors).
In neurons only, we observed diagnosis-specific glucocorticoid-induced changes in gene expression corresponding with PTSD-specific transcriptomic patterns found in human postmortem brains.
We observed glucocorticoid hypersensitivity in PTSD neurons, and identified genes that contribute to this PTSD-dependent glucocorticoid response. We find evidence of a coregulated network of transcription factors that mediates glucocorticoid hyper-responsivity in PTSD.
These findings suggest that induced neurons represent a platform for examining the molecular mechanisms underlying PTSD, identifying biomarkers of stress response, and conducting drug screening to identify new therapeutics.
Flint residents reported high rates of depression, PTSD years after water crisis
CNN
—
In a new study, researchers say the experiences of residents of Flint, Michigan, show that environmental disasters like the water crisis can have long-term consequences for mental health.
Flint residents reported changes to the water’s color, smell and taste soon after the city turned to the Flint River as a water source in April 2014. Following outraged pushback by residents and reports of children with mysterious illnesses, tests by the US Environmental Protection Agency and scientists at Virginia Tech detected dangerous levels of lead in the water.
For the new study, published in JAMA Network Open on Tuesday, nearly 2,000 adults living in Flint throughout the crisis were asked about their experiences, their psychological symptoms five years after the crisis and whether they had access to or used mental health services between August 2019 and April 2020. Most of the responses were gathered before the Covid-19 pandemic.
Researchers found that 1 in 5 Flint residents met the criteria for presumptive major depression, 1 in 4 for presumptive post-traumatic stress disorder (PTSD) and more than 1 in 10 for both disorders.
“Our findings from the study conducted with Flint residents five years after the water crisis indicate that Flint residents report extremely high levels of PTSD and depression, which are higher than rates found in Veterans post-deployment and US and global prevalence rates,” Angela Moreland-Johnson, one of the study authors and an assistant professor at the National Crime Victims Research and Treatment Center at the Medical University of South Carolina, told CNN in an email.
More than half of the people surveyed were women, and more than half of all respondents identified their race as Black or African American.
“Individuals who believed that their or their family’s health was moderately or greatly harmed by the water crisis were 123% more likely than their peers to have depression, 66% more likely to have PTSD, and 106% more likely to have comorbid depression and PTSD,” the study said.
According to the results, men were 28% less likely than women to meet the criteria for depression, and Black residents were offered more mental health services than White residents.
“The Flint community may require expanded mental health services to meet continued psychiatric need,” the researchers wrote in the study. “National disaster preparedness and response programs should consider psychiatric outcomes.”
The new study did not examine the mental health of residents in other communities such as Jackson, Mississippi, which recently experienced its own water crisis. But Moreland-Johnson said that the study’s results suggest that people involved in crises like Flint “may experience heightened PTSD and depression.”
The finding is especially relevant for those who experienced a potentially traumatic event before an environmental disaster, as “these prior experiences may place them at heightened risk for mental health concerns including PTSD and depression.”
Researchers said that communication with residents is key.
“Importantly, we found that people who experienced the greatest harm from the Flint crisis and those with low confidence in the information provided by authorities about water safety were significantly more likely to experience adverse mental health outcomes half a decade after the crisis,” study author Salma Abdalla, a research fellow with the Boston University School of Public Health, told CNN in an email.
Eight years after the water crisis began in Flint – even with new pipes and a different water source – some city residents recently told CNN they still don’t trust the water.
“I’ll never drink the water again,” said Audra Bell, whose family buys about 10 cases of bottled water a week for cooking, brushing teeth and making coffee and for them and their dogs to drink.
Their neighbor LeeAnne Walters says she does the same.
“There’s not been any justice in Flint. There has been no rebuilding of trust with the government because they haven’t done anything to do so. So the voices go unheard, and people have serious PTSD when it comes to water. I don’t know if there will ever be justice as far as Flint and the damage that’s been done to the people,” she told CNN.
Bell said the crisis has been hard on families, and choosing to stay in Flint hasn’t been an easy decision.
Her advice to Jackson residents: “Just do the best that you can, and keep your family safe.”
The water is back on in Jackson after historic flooding took out the water treatment plant where pumps were already failing. But problems for residents may linger.
Abdalla said the research in Flint “highlights the importance of early action following environmental disasters such as the current Jackson MS water crisis.”
“It showcases the importance of coupling efforts to fix the water supply system with clear communication by officials to restore trust in the safety of the system. Efforts should also include mental health recourses to those who need it,” Abdalla said.
CNN has contacted the city of Jackson to find out what options residents have for mental health support but did not immediately hear back. In a statement, the Mississippi Department of Mental Health said community mental health centers can provide therapy, peer support and intensive outpatient programs for people in need of psychiatric care and substance abuse treatment.
In a statement to CNN, study author Aaron Reuben, a postdoctoral fellow with the Medical University of South Carolina, said the new research “indicates that public works environmental disasters have a long tail, with psychological harms that can continue for many years if not treated.”
“Simply put, clean water is a requirement for health, well-being, productivity, and dignity – and we are failing our citizens in providing for this basic necessity. We feel that the residents of Flint who lived through the water crisis have been remarkably resilient – and yet there is still a large, unmet need for mental health services to address the psychological impacts of the event, which are reflected in very high rates of diagnosable depression and PTSD across the Flint community,” Reuben said.
“The lesson for communities like Jackson, MS, is to not overlook psychological injury, and to not assume that, just because community members are resilient, they could not benefit from services to address the psychological scars of a long-term water crisis.”
Johnny Depp-Amber Heard trial: Heard psychologist testifies to actress’s PTSD from Depp abuse
Depp is suing Heard for $50 million over a 2018 op-ed she wrote in The Washington Post, in which she said she had become a public figure representing domestic abuse. Depp has denied all claims of abuse.
Dawn Hughes, a forensic and clinical psychologist from New York City, said she evaluated Heard over 29 hours, multiple visits and a number of tests, and conducted interviews with her mother and other doctors. Hughes said based on her evaluation, she diagnosed Heard with post-traumatic stress disorder caused by intimate partner violence from Depp.
Hughes added that she disagreed with the findings and methods of Shannon Curry, a psychologist hired by Depp’s side who testified last week; Curry said she did not believe that Heard suffered from PTSD and found she was “exaggerating” her symptoms.
“Ms. Heard’s report of intimate partner violence and the records that I reviewed [are] consistent with what we know in the field about intimate partner violence, characterized by physical violence, psychological aggression, sexual violence, coercive control and surveillance behaviors,” Hughes said, when asked for her expert opinion.
Some tests she gave Heard specifically dealt with domestic violence, Hughes said, and she asked Heard what Depp did to her and what she did to him. “What these tests show was there was a high degree of serious violence perpetrated by Mr. Depp toward Ms. Heard; there was violence more on the mild level perpetrated by Ms. Heard,” Hughes said, adding that there was one “severe” indicator from Heard; she said the actress told her that she once punched Depp when he was “coming after” her sister.
Hughes spent part of her testimony discussing victims of abuse in general and why they don’t leave, and how a victim often feels like they can change their partner. She also spoke about Heard’s childhood, and said the actress was abused by her father, who had violent outbursts. That environment, Hughes said, taught Heard that “she could love someone who hurts her,” and to feel a need to help Depp, whose alcohol and drug use have become a talking point of the trial.
Heard did not deny the fact that she called Depp “horrible” names and insulted his parenting of his children, Hughes said, and she was remorseful of this; Hughes said Heard engaged in “minor forms of violence” such as pushing, shoving and throwing objects. But Hughes said in her opinion, she did not believe Heard was the perpetrator, and that those are common behaviors for women in similar situations. She said Heard described Depp verbally and psychologically abusing her, as well as exercising extreme control, such as calling directors or actors on her film sets and letting them know he had “eyes” everywhere. Hughes added that Heard suffered from anxiety and distress as she tried to navigate her career, because Depp would yell at her if she dressed a certain way, or accused her of cheating on him with co-stars.
According to Heard’s reports, Hughes said, Depp was physically and sexually violent toward her. She said Heard alleged that when Depp was drunk or high, he would throw her on the bed, tear off her nightgown and try to have sex with her. Heard told Hughes that when she and Depp were in Australia, during a fight, he grabbed an alcohol bottle from the bar and penetrated her with it. (A representative at the start of the trial said Heard’s claims of sexual assault were “fictitious.”)
Hughes said that Heard’s PTSD symptoms were made worse after Depp’s attorney called her sexual violence claims a hoax in April 2020. (She’s countersuing Depp for $100 million for defamation because of those comments.)
After the plaintiff’s side rested earlier Tuesday, Heard’s attorney, Benjamin Rottenborn, argued for the case to be dismissed. He said that Depp cannot prove Heard acted with “actual malice,” meaning that she knew what she wrote in the op-ed was false. He added there was “ample evidence” that Depp physically abused Heard; and though that’s in dispute by Heard’s side, he said, Depp’s own experts testified that abuse can come in many forms, from verbal to psychological. He pointed to some recordings that the jury heard of Depp shouting, and photos of messages he wrote in blood with his severed finger.
Depp’s attorney Benjamin Chew argued that Heard was the abuser in the relationship and said that repeated that she had defamed him with the op-ed even if she didn’t name him — under Virginia law, he said, it’s not necessary for the defamatory charge to be in direct terms, and “the implication was clear” that the article it was about Depp. He pointed to the testimony from the general counsel from the American Civil Liberties Union, which drafted the op-ed, who said some members of the organization worried that if they took out all references to Depp, the piece would not be as impactful.
Judge Penney Azcarate ultimately ruled that the case will go on. “If there is a scintilla of evidence that a reasonable juror could weigh, then the matter survives a motion to strike,” she said, adding that there has been enough evidence so far to continue. However, she said, she is waiting to rule on whether the article’s headline can remain part of the case (Heard’s lawyers said she didn’t write it) and whether it constituted “republishing” the headline when Heard tweeted the link to the op-ed.