Day: November 8, 2023

Categories : Injury & Trauma Mental HealthTags :

Glucocorticoid Levels Influence the Development of PTSD after Trauma

On By ModernMedia
Photo by Caleb Woods on Unsplash

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 : Genetics Mental HealthTags :

Scientists Identify Stress-linked Gene in Treatment-resistant Depression

On By ModernMedia
Photo by Andrew Neel on Unsplash

It has long been appreciated that major depressive disorder (MDD) has genetic as well as environmental influences. In a new study in Biological Psychiatry, researchers identify a gene that interacted with stress to mediate aspects of treatment-resistant MDD in an animal model.

Jing Zhang, PhD, at Fujian Medical University and senior author of the study, said, “Emerging evidence suggests that MDD is a consequence of the co-work of genetic risks and environmental factors, so it is crucial to explore how stress exposure and risk genes co-contribute to the pathogenesis of MDD.”

To do that, the authors used a mouse model of stress-induced depression called chronic social defeat stress (CSDS) in which mice are exposed to aggressor mice daily for two weeks. They focused on a gene called LHPP, which interacts with other signalling molecules at neuronal synapses. Increased expression of LHPP in the stressed mice aggravated the depression-like behaviours by decreasing expression of BDNF and PSD95 by dephosphorylating two protein kinases, CaMKIIα and ERK, under stress exposure.

Dr Zhang noted, “Interestingly, LHPP mutations (E56K, S57L) in humans can enhance CaMKIIα/ERK-BDNF/PSD95 signaling, which suggests that carrying LHPP mutations may have an antidepressant effect in the population.”

MDD is an extremely heterogeneous condition. Differences in the types of depression experienced by people influence the way they respond to treatment. A large subgroup of people with depression fail to respond to standard antidepressant medications and have “treatment-resistant” symptoms of depression. These patients often respond to different medications, such as ketamine or esketamine, or to electroconvulsive therapy. Notably, esketamine markedly alleviated LHPP-induced depression-like behaviours, whereas the traditional drug fluoxetine did not, suggesting that the mechanism might underlie some types of treatment-resistant depression.

John Krystal, MD, Editor of Biological Psychiatry, said of the work, “We have limited understanding of the neurobiology of treatment-resistant forms of depression. This study identifies a depression risk mechanism for stress-related behaviours that fail to respond to a standard antidepressant but respond well to ketamine. This may suggest that the risk mechanisms associated with the LHPP gene shed light on the poorly understood biology of treatment-resistant forms of depression.”

Dr Zhang added, “Together, our findings identify LHPP as an essential player driving stress-induced depression, implying targeting LHPP as an effective strategy in MDD therapeutics in the future.”

Source: Elsevier

Categories : Allergies COVIDTags :

Pre-existing Allergies Increase Risk of Experiencing Long COVID Symptoms

On By ModernMedia
Photo by Usman Yousaf on Unsplash

In an analysis of published prospective studies of people of all ages with confirmed SARS-CoV-2 infection who were followed for at least 12 months, pre-existing allergic conditions were linked to higher risks of experiencing long-term symptoms associated with COVID, or ‘Long COVID’.  

The analysis, which is published in Clinical & Experimental Allergy, identified 13 relevant studies (with a total of 9 967 participants) published between January 1, 2020 and January 19, 2023.

Although the data as a whole from the studies suggested that individuals with asthma or rhinitis might be at increased risk of long COVID after SARS-CoV-2 infection, the evidence for these associations was very uncertain. Therefore, more robust epidemiological research is needed to clarify the role of allergy in the development of Long COVID.

“We need a better, harmonised definition of what is considered Long COVID for epidemiological studies of this sort. Regardless we will be updating our analysis once further studies have been published in the next few months,” said corresponding author Christian Apfelbacher, PhD, of the Institute of Social Medicine and Health Systems Research, in Germany.

Source: Wiley

Categories : Cardiovascular DiseaseTags :

First Myocardial Damage-based Classification of Heart Attack is Released

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Pexels Photo by Freestocksorg

Heart attacks, or acute myocardial infarction (MI), are one of the leading causes of death worldwide. The newly released Canadian Cardiovascular Society Classification of Acute Myocardial Infarction (CCS-AMI) appearing in the Canadian Journal of Cardiology, published by Elsevier, presents a four-stage classification of heart attack based on heart muscle damage. This work by a group of noted experts has the potential to stratify risk more accurately in heart attack patients and lays the groundwork for development of new, injury-stage-specific and tissue pathology-based therapies.

Lead author Andreas Kumar, MD, MSc, Northern Ontario School of Medicine University, explains: “MI remains a leading cause of morbidity and mortality. Existing tools classify MIs using a patient’s clinical presentation and/or the cause of the heart attack, as well as ECG findings. Although these tools are very helpful to guide treatment, they do not consider details of the underlying tissue damage caused by the heart attack. This expert consensus, based on decades of data, is the first classification system of its kind ever released in Canada and internationally. It offers a more differentiated definition of heart attacks and improves our understanding of acute atherothrombotic MI. On a tissue level, not all heart attacks are the same; the new CCS-AMI classification paves the way for development of more refined therapies for MI, which could ultimately result in better patient clinical care and improved survival rates.”

The CCS-AMI classification describes damage to the heart muscle following an MI in four sequential and progressively severe stages. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. It is based on a strong body of evidence about the effect an MI has on the heart muscle.

As damage to the heart increases through each progressive CCS-AMI stage, patients have dramatically increased risk of complications such as arrhythmia, heart failure, and death. Appropriate therapy can potentially stop injury from progressing and halt the damage at an earlier stage.

  • Stage 1: Aborted MI (no/minimal myocardial necrosis). No or minimal damage to the heart muscle. In the best case the entire area of myocardium at risk may be salvaged.
  • Stage 2: MI with significant cardiomyocyte necrosis, but without microvascular injury. Damage to the heart muscle and no injury to small blood vessels in the heart. Revascularisation therapy will result in restoration of normal coronary flow.
  • Stage 3: MI with cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, “no-reflow”). Damage to the heart muscle and blockage of small blood vessels in the heart. The major adverse cardiac event rate is increased 2- to 4-fold at long-term follow-up.
  • Stage 4: MI with cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Damage to the heart muscle, blockage and rupture of small blood vessels resulting in bleeding into the heart muscle. This is a more severe form of microvascular injury, and the most severe form of ischemia-reperfusion injury. It is associated with a further increase in adverse cardiac event rate of 2- to 6-fold at long-term follow-up.

Dr Kumar concludes: “The new classification will help differentiate heart attacks according to the stage of tissue damage and allow healthcare providers to estimate a patient’s risk more precisely for arrhythmia, heart failure, and death. The CCS-AMI is ultimately expected to lead to better care, better recovery, and better survival rates for heart attack patients.”

In an accompanying editorial, Prakriti Gaba, MD, Brigham and Women’s Hospital, Harvard Medical School, and Deepak L. Bhatt, MD, MPH, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, comment: “Kumar et al. present a novel and intriguing four-tiered classification scheme of patients with acute MI. This allows unique utilisation of prognostic pathologic features to help distinguish between high and low risk acute MI patients. Greater access to cardiovascular magnetic resonance would be needed to implement this new clinical approach broadly, however, for research on emerging diagnostic and therapeutic strategies, it could be implemented immediately.”

Source: Elsevier

Categories : Expert Opinion Healthcare Politics and RegulationsTags :

Frank Dialogue on NHI: Medical Schemes are a Government Asset

On By ModernMedia

As the National Health Insurance (NHI) Bill makes its way through the approval process in the National Council of Provinces (NCOP), many actors in various sectors have called on the South African government to carefully consider the concerns raised regarding the proposed bill.

Stressing this point as one of the panellists in the Kwa-Zulu Natal leg of the Frank Dialogue on NHI hosted by media anchor and Leadership magazine editor, Prof JJ Tabane, and his team, recently in Umhlanga, Dr Katlego Mothudi, Board of Healthcare Funders (BHF) MD, acknowledged that both the public and the private sectors were not perfect, but cited that destroying the private sector was not going to accelerate the attainment of the global agenda of Universal Health Coverage. Strengthening a health system requires reform of six pillars; and the National Health Insurance formed part of the finance pillar only. He further noted that the private sector was a national asset to contribute to the success of health reform.

Other participants in the dialogue were the Minister of Health, Dr Joe Phaahla, Dr Kgosi Letlape (former Health Professions Council of SA and SA Medical Association chair), Zwelinzima Vavi (SA Federation of Trade Unions chair), Dr Nicholas Crisp (Department of Health Deputy-Director: NHI), and Nozibele Tshobeni (Sizwe Hosmed Acting PO).

The primary aim of these events has been to facilitate a constructive and inclusive discourse among various professionals in the sector, with the Minister of Health, regarding the proposed NHI Bill. 

Emphasising the importance of overcoming several issues before the Bill could be successfully rolled out, Prof Tabane acknowledged that the health crisis in South Africa was of significant concern, rendering the implementation of universal health coverage (UHC) a necessity.

Asked about the future role of medical schemes under NHI, Crisp reiterated that NHI was not about scrapping medical aids, but about the right of all South Africans to access affordable healthcare: “The bill does not abolish or repeal the National Health Act. It merely goes about a different way of financing – a single fund to care for the majority of the health benefits that we need as a nation to strive.

However, Dr Mothudi disagreed with Crisp and highlighting that a multi-payer system was a better model given the south African context that has load of fraud and corruption.  “Why not a multi-payer system, as originally proposed in the first NHI Green Paper?” he asked.

“Between now and that point,” Crisp explained, “we need the medical schemes to continue what they are doing but to do it more effectively than they are doing at present. They criticised us in the Health Market Inquiry, saying we did not provide leadership. Now we are providing leadership – we want to have a multilateral negotiating forum, we want to set prices, want to introduce other related measures:

A moot point made by Sizwe Hosmed’s Ms Tshobeni in her concluding remarks was that while she agreed that NHI was “overall, a good idea”, pushing the Bill through was putting the cart before the horse: “How we are going about it is really the problem.

“We are not that far apart in our discussions on this, but where we are drifting apart can be answered by the question ‘why are we here?’” asked Dr Mothudi.

“Going on blaming apartheid etc is not good. The Medical Schemes Act, for example, was promulgated in 1998 – post-apartheid. So, we must take responsibility for these challenges. Secondly, Government must provide stewardship, being responsible for the lives and healthcare of every citizen. Right now, we only have one Department of Health, not one for the public and one for the private sector.”

Also noted was that the private sector “does not run itself”. The National Health Act is there to guide practitioners and establishments how they should behave, while the Medical Schemes Act is enforced by the Council for Medical Schemes under stewardship of Department of Health.

While many views were expressed about the pros and cons of NHI, among the most common once again were, as already mentioned, the wisdom of a single payer system. Contributing his views on this, the BHF’s Dr Mothudi revived the originally drafted concept of a multipayer system for the fund: “A multipayer system was proposed in the first NHI Green Paper but was thrown out! A multipayer system would work in the same way as it did during the COVID vaccination campaign. When standing in the vaccination queue you wouldn’t know who was paying for the service for the person in front of you – employer, medical aid, or government?

“The pricing and service for the vaccine and procedure,” he said, “was set the same for all and for everyone.”

To watch the Frank Dialogue Click Here