Tag: PTSD

Categories : Injury & Trauma Mental HealthTags :

Glucocorticoid Levels Influence the Development of PTSD after Trauma

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Posttraumatic stress disorder (PTSD) is a debilitating condition that arises after experiencing traumatic events. While many people experience trauma, only about 25–35% of them develop PTSD. Understanding the factors that make certain individuals more susceptible is crucial for both prevention and treatment.

A new study led by Carmen Sandi and Simone Astori at EPFL now reveals how the development of PTSD is influenced by glucocorticoids, which are stress hormones such as cortisol. The work, which is published in Biological Psychiatry, provides significant insights into the behavioural and biological traits associated with PTSD vulnerability.

“There are considerable differences in the levels of glucocorticoids that individuals release to the bloodstream when stressed,” says Carmen Sandi. “Low glucocorticoid levels are frequently observed in PTSD patients following trauma exposure and were initially suspected to be a consequence of trauma exposure.”

She continues: “The possibility that this could be a trait constituting a pre-existing 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.”

To explore how a reduced hormonal response to stress might be linked to PTSD symptoms, the researchers used a genetically selected rat model that mimics people with blunted responses to cortisol. To do this, the team used MRI scans to measure the volume of different brain regions, trained rats to associate a cue with fear, recorded their sleep patterns, and measured their brain activity.

By combining these methods, the researchers discovered that a blunted responsiveness to glucocorticoids led to a “correlated multi-trait response” that includes impaired fear extinction (in males), reduced hippocampal volume, and rapid-eye movement sleep disturbances.

To explain the terms: Fear extinction is a process by which a conditioned fear response diminishes over time; problems with fear extinction are a hallmark of PTSD. Rapid-eye movement is crucial for memory consolidation, and disturbances in this type of sleep pattern have long been associated with PTSD.

But the study didn’t end there: the researchers treated the rats with the equivalent of human cognitive and behavioral therapy to reduce their learned fears. After that, they gave the rats corticosterone. As a result, both excessive fear and disturbances in rapid-eye movement sleep receded. Not only that, but the increased levels of the stress-related neurotransmitter norepinephrine in the brain also 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,” says Carmen Sandi. “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.”

Silvia Monari, the study’s first author, adds: “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.”

Source: Ecole Polytechnique Fédérale de Lausanne

Categories : Mental HealthTags :

Cognitive Behavioural Therapy over The Internet is Effective for PTSD

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In a large-scale randomised controlled trial, researchers from the UK and Sweden have shown that internet-mediated cognitive behavioural therapy (CBT) can provide results for post-traumatic stress disorder (PTSD) that are in line with conventional face-to-face care. The article, which was recently published in Lancet Psychiatry, also shows that the time required for therapists is greatly reduced, which could mean that more patients can be treated and have access to the right help.

Common symptoms include reliving the trauma, overexcitement, avoidance and emotional and cognitive consequences, such as depression and difficulty concentrating. Psychological treatment in the form of CBT has been shown to have good effects in PTSD, but access to care is limited and varies between different places.

Post-traumatic stress disorder (PTSD) is a psychiatric diagnosis that affects about 5-10% of the population. PTSD occurs as a result of experiencing – or witnessing – severe, life-threatening and traumatic events, such as abuse, war, accidents and mistreatment.

The study recruited 217 participants through the NHS or self-referral. Mean age was 36·36 years, with a range 18–71 years; 158 (73%) self-reported as female, 57 (26%) as male, and two (1%) as other. Of these, 52 (24%) participants met self-reported criteria for ICD-11 complex PTSD.  The advantages in outcome for internet-mediated therapy were greater for participants with high dissociation or complex PTSD symptoms, and mediation analyses showed both treatments worked by changing negative meanings of the trauma, unhelpful coping, and flashback memories. No serious adverse events were reported.

Source: Karolinska Institutet

Categories : Mental Health NeurologyTags :

Why do People Remember Emotional Events Better?

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Most people remember emotional events, like their wedding day, very clearly, but researchers are not sure how the human brain prioritises emotional events in memory. In a study published in Nature Human Behaviour, Joshua Jacobs, associate professor of biomedical engineering at Columbia Engineering, and his team identified a specific neural mechanism in the human brain that tags information with emotional associations for enhanced memory.

The team demonstrated that high-frequency brain waves in the amygdala, a hub for emotional processes, and the hippocampus, a hub for memory processes, are critical to enhancing memory for emotional stimuli. Disruptions to this neural mechanism, brought on either by electrical brain stimulation or depression, impair memory specifically for emotional stimuli.

Rising prevalence of memory disorders

The rising prevalence of memory disorders such as dementia has highlighted the damaging effects that memory loss has on individuals and society. Disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD) can also feature imbalanced memory processes, especially with the COVID pandemic. Understanding how the brain naturally regulates what information gets prioritised for storage and what fades away could provide critical insight for developing new therapeutic approaches to strengthening memory for those at risk of memory loss, or for normalising memory processes in those at risk of dysregulation.

“It’s easier to remember emotional events, like the birth of your child, than other events from around the same time,” says Salman E. Qasim, lead author of the study, who started this project during his PhD in Jacobs’ lab at Columbia Engineering. “The brain clearly has a natural mechanism for strengthening certain memories, and we wanted to identify it.”

The difficulty of studying neural mechanisms in humans

Most investigations into neural mechanisms take place in animals such as rats, because such studies require direct access to the brain to record brain activity and perform experiments that demonstrate causality, such as careful disruption of neural circuits. But it is difficult to observe or characterise a complex cognitive phenomenon like emotional memory enhancement in animal studies.

To study this process directly in humans. Qasim and Jacobs analysed data from memory experiments conducted with epilepsy patients undergoing direct, intracranial brain recording for seizure localisation and treatment. During these recordings, epilepsy patients memorised lists of words while the electrodes placed in their hippocampus and amygdala recorded the brain’s electrical activity.

Studying brain-wave patterns of emotional words

Qasim found that participants remembered more emotionally rated words, such as “dog” or “knife,” better than more neutral words, such as “chair.” Whenever participants successfully remembered emotional words, high-frequency neural activity (30-128 Hz) would become more prevalent in the amygdala-hippocampal circuit, a pattern which was absent when participants remembered more neutral words, or failed to remember a word altogether. Analysing 147 participant, they found a clear link between participants’ enhanced memory for emotional words and the prevalence in their brains of high-frequency brain waves across the amygdala-hippocampal circuit.

“Finding this pattern of brain activity linking emotions and memory was very exciting to us, because prior research has shown how important high-frequency activity in the hippocampus is to non-emotional memory,” said Jacobs. “It immediately cued us to think about the more general, causal implications – if we elicit high-frequency activity in this circuit, using therapeutic interventions, will we be able to strengthen memories at will?”

Electrical stimulation disrupts memory for emotional words

In order to establish whether this high-frequency activity actually reflected a causal mechanism, Jacobs and his team formulated a unique approach to replicate the kind of experimental disruptions typically reserved for animal research. First, they analysed a subset of these patients who had performed the memory task while direct electrical stimulation was applied to the hippocampus for half of the words that participants had to memorise. They found that electrical stimulation, which has a mixed history of either benefiting or diminishing memory depending on its usage, clearly and consistently impaired memory specifically for emotional words.

Uma Mohan, another PhD student in Jacobs’ lab at the time and co-author on the paper, noted that this stimulation also diminished high-frequency activity in the hippocampus. This provided causal evidence that, by knocking out the brain activity pattern correlating with emotional memory, stimulation was also selectively diminishing emotional memory.

Depression acts similarly to brain stimulation

Qasim further hypothesized that depression, which can involve dysregulated emotional memory, might act similarly to brain stimulation. He analyzed patients’ emotional memory in parallel with mood assessments the patients took to characterize their psychiatric state. And, in fact, in the subset of patients with depression, the team observed a concurrent decrease in emotion-mediated memory and high-frequency activity in the hippocampus and amygdala.

“By combining stimulation, recording, and psychometric assessment, they were able to demonstrate causality to a degree that you don’t always see in studies with human brain recordings,” said Bradley Lega, a neurosurgeon and scientist at the University of Texas Southwestern Medical Center and not an author on the paper. “We know high-frequency activity is associated with neuronal firing, so these findings open new avenues of research in humans and animals about how certain stimuli engage neurons in memory circuits.”

Next steps

Qasim is now investigating how individual neurons in the human brain fire during emotional memory processes. Qasim and Jacobs hope that their work might also inspire animal research exploring how this high-frequency activity is linked to norepinephrine, a neurotransmitter linked to attentional processes that they theorise might be behind the enhanced memory for emotional stimuli. They also hope that future research will target high-frequency activity in the amygdala-hippocampal circuit to protect memory.

“Our emotional memories are one of the most critical aspects of the human experience, informing everything from our decisions to our entire personality,” Qasim added. “Any steps we can take to mitigate their loss in memory disorders or prevent their hijacking in psychiatric disorders is hugely exciting.”

Source: Columbia University School of Engineering and Applied Science.

Categories : Cardiovascular Disease Mental HealthTags :

Blood Pressure Drug may Help Fight PTSD

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Research published in the journal Molecular Psychiatry suggest that clonidine, a 50-year-old blood pressure drug, 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.

Clonidine is commonly used as a hypertension 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.

Laboratory evidence shows that while the two drugs bind to the same receptors, they do different things there, says Qin Wang, MD, PhD, neuropharmacologist and founding director of the Program for Alzheimer’s Therapeutics Discovery at MCG.

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, they found that a novel axis on an adrenergic receptor called ɑ2A is essential to maintaining fear memories which associate a place or situation, like the site of a horrific car accident, 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. 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 behaviour.

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 restabilises, 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, with only two approved specifically for the condition, she says. The lack of approved drugs has led to off-label uses of drugs like clonidine.

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.

Source: Medical College of Georgia at Augusta University

Categories : Mental HealthTags :

Morning Blue Light Exposure Eases PTSD Symptoms and Aids Sleep

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After being treated with a course of blue light exposure in the morning, people with post-traumatic stress disorder (PTSD) experienced better sleep, a reduction in the severity of PTSD symptoms and had more effective treatments overall, according to a new study recently published in Frontiers in Behavioral Neuroscience.

Sleep is crucial for maintaining physical and mental health, and inadequate sleep over time can impact all aspects of life with serious implications for long-term health, relationships, cognitive abilities such as learning, and healing.

The influence of sleep disruption on PTSD symptom severity is well established. Those who seek treatment to allay their PTSD symptoms often face a vicious cycle where poor sleep interferes with the effectiveness of treatments, negating any lessening of symptoms, which in turn contributes to sleep disruptions. To reduce and eliminate the emotional impact of traumatic memories, the patient needs quality sleep to integrate healing mechanisms achieved through cognitive or exposure therapy treatments.

“This research is exciting and unique because it points to an easy-to-use method for helping those with PTSD to retain the benefits of therapy long after the treatment ends,” said psychiatry professor William “Scott” Killgore, PhD, senior author on the paper, “Morning blue light treatment improves sleep complaints, symptom severity, and retention of fear extinction memory in post-traumatic stress disorder.”

Dr Killgore and the SCAN Lab team conducted a comprehensive assessment of daily morning blue-wavelength light exposure on individuals with clinically significant levels of PTSD. The goal was to ascertain if blue light therapy would help improve sleep and PTSD symptoms and sustain learned fear extinction memories, an analogue of therapeutic treatment for trauma.

Study participants committed to 30 minutes of morning light exposure daily for six weeks, with half of the participants using blue-wavelength light and half using amber light. Researchers examined the neurobiological, autonomic and behavioural outcome changes during the study.

The 43 participants who received blue light therapy not only demonstrated significant improvements in the severity of their PTSD symptoms, but also reported improvements in sleep and showed an increased retention of fear extinction memories. The control 39 controls receiving amber light did not show the same retention of the extinction memories, but rather showed a return of the original fear memories.

“While the limitations of the research include its modest sample size and difficulties monitoring compliance, the possibilities of utilising a treatment that is relatively simple, drug-free and inexpensive can offer hope for the large population of people living with the intense challenges of post-traumatic stress disorder,” Dr Killgore said.

Source: University of Arizona Health Sciences

Categories : Gender Mental HealthTags :

Menstrual Cycles May Impact PTSD Symptoms in Women

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New research has found that post-traumatic stress disorder symptoms in women may vary over the course of the menstrual cycle, with more symptoms during the cycle’s first few days when the hormone oestradiol is low and fewer symptoms close to ovulation, when oestradiol is high.

The results could have implications for PTSD diagnosis and treatment, said lead author Jenna Rieder, PhD, an assistant professor of psychology at Thomas Jefferson University in Philadelphia. “When in the cycle you assess women might actually affect whether they meet diagnostic criteria for PTSD, especially for people who are right on the border. And that can have real practical implications, say, for someone who is a veteran and entitled to benefits or for health insurance purposes.”

The research was published in the journal Psychological Trauma: Theory, Research, Practice and Policy.

Oestradiol is a form of oestrogen that regulates the menstrual cycle. During the follicular phase, rising oestradiol levels trigger a cascade of events that result in ovulation. Studies have linked low-oestradiol portions of the cycle to greater activation in the limbic areas of the brain, which are related to emotion, and to lower activation in the prefrontal cortex when viewing emotional content. Low oestradiol has also been linked to greater stress and anxiety as well as increased fear responses.

To find out whether those links were related to traua response, researchers studied 40 women, aged 18 to 33, all of whom had experienced or witnessed a traumatic event, such as a serious injury or sexual violence. In the lab, researchers measured the participants’ level of oestradiol in their saliva, then asked them to describe the trauma that had happened to them and the PTSD symptoms they’d experienced in the past month. They found that lower oestradiol was associated with greater self-reported symptom severity in the participants.

The researchers also measured two stress biomarkers in participants’ saliva, the hormone cortisol and the enzyme salivary alpha-amylase, before and after the participants described their trauma. Salivary alpha-amylase is related to the “fight-or-flight” stress response, and cortisol is related to the body’s slower, more sustained stress response.

“In a healthy system we want a moderate, coordinated response of both of these biomarkers,” Prof Rieder said. In the women in the low-oestradiol portions of their menstrual cycles, the researchers instead found low cortisol and high salivary alpha-amylase levels resulting from recounting their trauma stories – a pattern that’s been linked in previous studies with maladaptive stress responses.

The researchers then asked the participants to answer five daily questionnaires for 10 days spanning the high- and low-oestradiol portions of their menstrual cycles. The questionnaires measured how participants were feeling at each time (from “extremely unpleasant” to “extremely pleasant” and “extremely nonstimulated or activated” to “extremely stimulated or activated”). Participants also completed a PTSD symptom checklist each evening.

Participants were found to have greater variability in their daily moods during the low-oestradiol days of their cycle and reported more severe PTSD symptoms on those days.

This could have implications for diagnosis and treatment of PTSD in women, who have long been underrepresented in PTSD research. “PTSD for a long time was mostly studied in men, in part because it was mainly studied in veterans, who were mostly men,” Prof Rieder said.

As well as its relevance to diagnosis, knowing how the menstrual cycle affects PTSD symptoms could be useful for both clinicians and patients, according to Prof Rieder. “I think this is something that clinicians would want to know, so they can impart this knowledge as part of psychoeducation,” she said. “For women who are naturally cycling, it may be useful to understand how the menstrual cycle affects their symptoms. When you can explain what’s happening biologically, it often becomes less threatening.”

Source: American Psychological Association

Categories : Pain ManagementTags :

Patient Awake for 13 Minutes During Surgery

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A patient in the US was awake for 13 minutes of his surgery because apparently his anaesthetic was never turned on.

In mid-2020 the patient, Matthew Caswell went into Progress West Hospital in O’Fallon, Missouri, for hernia repair and removal of a lipoma on the back of his neck.

However, he soon became aware that something was amiss.

“I knew I was in trouble when I felt the cold iodine hit my belly and they were scrubbing me off. At any second I was waiting to go out, but all of a sudden I just got stabbed in my stomach,” Caswell told local TV station KCTV.

Caswell’s lawyer Kenneth Vuylsteke told MedPage Today that a paralytic agent had already been given to his client, and then the mask was put on to receive sevoflurane for general anaesthesia, but the flow of the gas was never started.

Caswell able to feel pain and hear operating room conversation for 13 minutes, he told KCTV.

During this, his vital signs surged, said Vuylsteke. Records shared with MedPage Today show a baseline heart rate in the 65 to 70 range, which skyrocketed to 115 beats per minute within a few minutes of the first incision.

After the first incision, Caswell’s blood pressure also shot up, from a baseline of 113/73 mm Hg to 158/113 mm Hg — severe hypertension.

Vuylsteke noted that hat should have been ample warning that something was likely wrong with the anaesthetic.

What he gathered so far is that Caswell was brought into the operating room and given the paralytic agent. The anaesthesiologist or the nurse anesthetist put the anaesthetic mask on him, but then the surgeon requested to see the lipoma before starting.

Caswell was turned over so the surgeon could see the lipoma. He was then put onto his back again, and the mask was put back on, but the sevoflurane was never turned on, Vuylsteke said.

A “Significant Event Note” is in hospital records that acknowledges that a “review of the anesthetic record demonstrates a delay in initiating inhalational anesthetic after induction of anesthesia.”

The note indicates that Caswell and his mother were “immediately informed regarding the delay in initiating the inhaled anesthetic agent until after the start of the surgical procedure.” The hospital “provided emotional support and discussed our intention to ensure his pain and anxiety over the event were well controlled in the immediate term.” The hospital also recommended a psychology consult for which they would cover the cost.

Caswell charges that he’s suffering from post-traumatic stress disorder and panic attacks because of the experience.

He’s suing the anaesthesiologist, the nurse anaesthetist Kathleen and also their employer, Washington University in St Louis.

“I would have rather died on that table,” he told KCTV.

Source: MedPage Today