Tag: 31/3/25

Categories : Mental HealthTags : Leave a comment

Three Quarters of People Who Have Taken Antidepressants Say They Were Helpful

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Photo by Danilo Alvesd on Unsplash

About 75% of a sample of nearly 20 000 people who have taken selective serotonin reuptake inhibitors (SSRIs) report they found them helpful, according to new research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London.

Published in Psychological Medicine, the study explored different factors that could explain why SSRIs work for some people with major depressive disorder, but not others.

Researchers analysed data from UK Biobank on 19 516 participants who had tried at least one SSRI, such as citalopram, fluoxetine, paroxetine or sertraline, for at least two weeks. Participants reported whether the SSRI helped them “feel better” using a single item questionnaire with possible responses “yes, at least a little”, “no”, “do not know”, or “prefer not to answer”. This is the first detailed analysis of this large-scale study which assesses SSRIs using self-reported experiences rather than clinician-reported remission from symptoms.

Overall, 74.9% felt SSRIs helped them feel better. 18.8% said the prescribed drug was not helpful.

Using a range of data collected by UK Biobank, the study analysed what factors might influence whether people found SSRIs helpful.

It found that sociodemographic factors such as age, gender and household income were linked to differences in how people perceived the effectiveness of SSRIs. Those participants who were older, male, had lower incomes, and reported alcohol or illicit drug use were more likely to say that they did not find antidepressants helpful.

Participants who had experienced no mood improvement even when positive events occurred or whose worst episode of depression lasted more than two years, were also less likely to report that SSRIs were helpful. Lastly those who had a greater genetic risk for depression, calculated using polygenic risk scores, were less likely to report that SSRIs were helpful.

The use of antidepressants, and the rate at which they are prescribed in the UK, has been the source of much debate both in the public and media. While antidepressants don’t work for every user, this research provides reassuring evidence that many people report that this common type of medication is helping them manage what can be a severe illness.

Dr Michelle Kamp, Postdoctoral Research Associate at King’s IoPPN and first author on the study

We know that not all people respond to antidepressants prescribed, but most studies have focussed on clinician’s perspectives of response. Using participant reports, we found a strong support for antidepressants, with three quarters of people saying the drugs had helped them. The factors that make people more likely to respond to antidepressants mirror findings in clinical trials which use measures reported by clinicians. This suggests that patient-focussed responses can capture valuable insights into the effectiveness of antidepressants.

Professor Cathryn Lewis, Professor of Genetic Epidemiology & Statistics at King’s IoPPN and senior author on the study

Professor Andrew McIntosh, Professor of Biological Psychiatry at the University of Edinburgh’s Centre for Clinical Brain Sciences and co-investigator on the study, said: “The findings from this large study show that nearly three-quarters of people in UK Biobank who were treated with antidepressants found them helpful. There is already excellent evidence from clinical trials that antidepressants work for people with depression. However those studies focus on addressing only whether they are more effective than placebos, and not why they are more effective in some people than others. We must now focus on developing a better understanding of how antidepressants work and how we can predict which people are most likely to benefit from these treatments.”

The study offers key insights into antidepressant response, however the sample may not fully represent the general population and reliance on retrospective self-reports can lead to inaccurate recollection.

Source: King’s College London

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Shorter, Higher-dose Radiotherapy for Prostate Cancer Delivers Promising Results

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Photo by Jo McNamara

A new large-scale study co-led by UCLA Health Jonsson Comprehensive Cancer Center investigators provides the strongest evidence yet that a shorter, standard-dose course radiation treatment is just as effective as conventional radiotherapy for early-stage prostate cancer, without compromising the safety of patients.

The shorter approach, known as isodose moderately hypofractionated radiotherapy (MHFRT), delivers slightly higher doses of radiation per session, allowing the total treatment duration to be over four to five weeks instead of seven to eight weeks.

According to the study, patients who received this type of MHFRT had the same cancer control rates as those who received conventional radiotherapy. Additionally, the risk of long-term side effects affecting the bladder and intestines was no higher with MHFRT, confirming its safety. 

The findings were published in the Lancet Oncology.

“We believe these data strongly support that isodose MHFRT should become the preferred standard of care MHFRT regimen for prostate cancer,” said Dr Amar Kishan, executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA and co-first author of the study. “More broadly, there appears to be little reason to consider conventional radiotherapy over MHFRT for the types of patients enrolled in these trials given these results.”

While MHFRT is now the most commonly used radiotherapy regimen for prostate cancer, concerns remain about whether delivering a higher daily dose increases the risk of urinary and bowel issues, such urinary incontinence, chronic diarrhoea and rectal bleeding.

MHFRT: isodose versus dose-escalated

To better understand whether there might be an increased risk of toxicity with the delivery of a higher dose per day of radiation, Kishan and the team of researchers examined data from more than 5800 patients across seven randomised clinical trials comparing standard therapy with two different MHFRT approaches: isodose MHFRT, which maintains the total radiation dose at a level similar to standard therapy, and dose-escalated MHFRT, which increases the total dose in hopes of enhancing tumour control.

The analysis found patients who received isodose MHFRT (60Gy in 20 fractions) had similar cancer control and side effects compared to those receiving conventional radiation therapy, with no significant difference in the five-year progression-free survival (77.0% for MHFRT vs 75.6% for conventional).

Patients who received higher dose-escalated MHFRT did not improve cancer control when compared to those receiving standard doses, with five-year progression-free survival rates being identical to conventional therapy (82.7% in both groups). Patient-reported outcomes also showed significantly higher gastrointestinal side effects (7.2% vs 4.9%), particularly bowel issues. 

While dose-escalated MHFRT was expected to improve outcomes, the data showed no additional benefit in cancer control and a higher risk of gastrointestinal side effects, noted Kishan. This underscores the advantage of isodose MHFRT, which provides the same effectiveness as conventional therapy without increasing toxicity.

“These findings reinforce isodose MHFRT as the standard of care, offering the same cancer control as conventional treatment but with fewer side effects than dose-escalated MHFRT,” said Kishan, who is also a researcher in the UCLA Health Jonsson Comprehensive Cancer Center. “Patients can safely opt for a shorter treatment schedule without compromising their outcomes, ensuring they receive effective care with fewer visits and minimal added risk. Less time in treatment can still mean the best possible results.”

Source: University of California – Los Angeles Health Sciences

Categories : NeurologyTags : Leave a comment

An Arthritis Drug Might Unlock Lasting Relief from Epilepsy and Seizures

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Source: Pixabay

A drug typically prescribed for arthritis halts brain-damaging seizures in mice that have a condition like epilepsy, according to researchers at the University of Wisconsin–Madison. The drug, called tofacitinib, also restores short-term and working memory lost to epilepsy in the mice and reduces inflammation in the brain caused by the disease.

If the drug proves viable for human patients, it would be the first to provide lasting relief from seizures even after they stopped taking it.

“It ticks all the boxes of everything we’ve been looking for,” says Avtar Roopra, a neuroscience professor in the UW–Madison School of Medicine and Public Health and senior author of the study, which appears in Science Translational Medicine.

Epilepsy is one of the most common neurological diseases, afflicting more than 50 million people around the world. While there are many known causes, the disease often appears after an injury to the brain, like a physical impact or a stroke.

Some days, months or even years after the injury, the brain loses the ability to calm its own activity. Normally balanced electrical activity through the brain goes haywire.

“The system revs up until all the neurons are firing all the time, synchronously,” says Roopra. “That’s a seizure that can cause massive cell death.”

And the seizures repeat, often at random intervals, forever. Some drugs have been useful in addressing seizure symptoms, protecting patients from some of the rampant inflammation and memory loss, but one-third of epilepsy patients do not respond to any known drugs, according to Olivia Hoffman, lead author of the study and a postdoctoral researcher in Roopra’s lab. The only way to stop the most damaging seizures has been to remove a piece of the brain where disruptive activity starts.

On their way to identifying tofacitinib’s potential in epilepsy, Hoffman and co-authors used relatively new data science methods to sift through the way thousands of genes were expressed in millions of cells in the brains of mice with and without epilepsy. They found a protein called STAT3, key to a cell signaling pathway called JAK, at the centre of activity in the seizure-affected mouse brains.

“When we did a similar analysis of data from brain tissue removed from humans with epilepsy, we found that was also driven by STAT3,” Hoffman says.

Meanwhile, Hoffman had unearthed a study of tens of thousands of arthritis patients in Taiwan aimed at describing other diseases associated with arthritis. It turns out, epilepsy was much more common among those arthritis patients than people without arthritis — but surprisingly less common than normal for the arthritis patients who had been taking anti-inflammatory drugs for more than five-and-a-half years.

“If you’ve had rheumatoid arthritis for that long, your doctor has probably put you on what’s called a JAK-inhibitor, a drug that’s targeting this signaling pathway we’re thinking is really important in epilepsy,” Hoffman says.

The UW researchers ran a trial with their mice, dosing them with the JAK-inhibitor tofacitinib following the administration of a brain-damaging drug that puts them on the road to repeated seizures. Nothing happened. The mice still developed epilepsy like human patients.

Remember, though, that epilepsy doesn’t often present right after a brain-damaging event. It can take years. In the lab mice, there’s usually a lull of weeks of relatively normal time between the brain damage and what the researchers call “reignition” of seizures. If it’s not really epilepsy until reignition, what if they tried the drug then? They devised a 10-day course of tofacitinib to start when the mouse brains fell out of their lull and back into the chaos of seizures.

“Honestly, I didn’t think it was going to work,” Hoffman says. “But we believe that initial event sort of primes this pathway in the brain for trouble. And when we stepped in at that reignition point, the animals responded.”

The drug worked better than they could have imagined. After treatment, the mice stayed seizure-free for two months, according to the paper. Collaborators at Tufts University and Emory University tried the drug with their own mouse models of slightly different versions of epilepsy and got the same, seizure-free results.

Roopra’s lab has since followed mice that were seizure-free for four and five months. And their working memory returned.

“These animals are having many seizures a day. They cannot navigate mazes. Behaviourally, they are bereft. They can’t behave like normal mice, just like humans who have chronic epilepsy have deficits in learning and memory and problems with everyday tasks,” Roopra says. “We gave them that drug, and the seizures disappear. But their cognition also comes back online, which is astounding. The drug appears to be working on multiple brain systems simultaneously to bring everything under control, as compared to other drugs, which only try to force one component back into control.”

Because tofacitinib is already FDA-approved as safe for human use for arthritis, the path from animal studies to human trials may be shorter than it would be for a brand-new drug. The next steps toward human patients largely await NIH review of new studies, which have been paused indefinitely amid changes at the agency.

For now, the researchers are focused on trying to identify which types of brain cells are shifted back to healthy behavior by tofacitinib and on animal studies of even more of the many types of epilepsy. Hoffman and Roopra have also filed for a patent on the use of the drug in epilepsy.

Source: University of Wisconsin-Madison

Categories : Respiratory DiseasesTags : Leave a comment

Immune Cell Networks Found to be Driving Idiopathic Pulmonary Fibrosis

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Photo by Robina Weermeijer on Unsplash

Rutgers Health researchers have discovered that networks of misplaced immune cells drive an aggressive lung disease, potentially opening a path to new treatments for a condition that kills 80% of patients within a decade.

Idiopathic pulmonary fibrosis (IPF) scars lung tissue and makes breathing increasingly difficult until patients can’t get enough oxygen. Available drugs provide minimal benefit. Lung transplantation works for some patients, but transplants have a 50% five-year mortality rate.

This study in the European Respiratory Journal used advanced spatial mapping techniques to compare healthy lung tissues and tissues from patients with fatal IPF. The researchers discovered that disease-scarred lung tissue abounds in plasma cells – specialised immune cells that typically reside in bone marrow and produce antibodies.

“What we found most striking in this study is that all the fibrotic regions of IPF patients’ lungs are covered by antibody-producing plasma cells,” Qi Yang, an associate paediatrics professor at Rutgers and a senior author of the study. “In normal lungs, there are almost no plasma cells. But in IPF patients, the lungs are full of them.”

The researchers identified previously unknown cellular networks orchestrating this abnormal immune response. They discovered novel mural cells wrapping around blood vessels and producing signal proteins that organize immune responses. They also found unique fibroblasts secreting a protein that attracts plasma cells to damaged areas.

“This particular type of fibroblast has never been described before,” said Reynold Panettieri, director of the Rutgers Institute for Translational Medicine and Science and a senior author of the study. “People have shown that fibroblasts are the cell types responsible for scarring – in the skin, the lungs and the brain – but this particular type of fibroblast seems unique to the lung.”

Having found the plasma cells in lung tissue taken from people who died of IPF, the team began using live mice to see if reducing plasma in the lungs slowed disease formation. This work demonstrated that blocking signaling pathways reduced plasma cell accumulation and alleviated lung scarring. Targeting these same signaling pathways may thus prove an effective disease treatment in humans, the researchers said.

The research is particularly promising because drugs targeting plasma cells already exist. Medications used to treat multiple myeloma, a plasma cell cancer, could potentially be repurposed to treat IPF.

“If the plasma cells are really making the bad antibodies, I assume we may have to get rid of them,” said Yang, a member of the Institute for Translational Medicine and Science. “Otherwise, patients will keep making these antibodies that drive the disease.”

Previous studies have shown that IPF patients have heightened antibody responses and elevated lung antibody levels. The new research explains the origin of these antibodies and reveals how abnormal antibody-producing cells accumulate in the lungs.

The researchers said the antibodies may drive tissue damage through several mechanisms. Their data suggest that antibody-antigen complexes stimulate the production of transforming growth factor-beta from pulmonary macrophages, thus promoting fibrosis.

“Now that we have a target, a cell, a unique cell that Dr Yang has identified and phenotyped, we’re optimistic that we could affect that cell and not other fibroblasts that are important in normal injury repair response,” Panettieri said.

For patients with IPF, the findings offer hope of new treatments for a debilitating condition with limited therapeutic options. The disease typically affects men over 60 years of age, with most patients dying within five years of diagnosis.

The next steps for the research team include determining whether the plasma cells are producing autoantibodies against healthy tissues and further investigating how fibroblasts and mural cells develop their abnormal properties in IPF.

“Our research suggests that IPF might have a strong autoimmune link,” Yang said.

Source: Rutgers University

Categories : Environmental EffectsTags : Leave a comment

Cold Plunges Fire up Repair Functions in Cells

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Photo by Yaroslav Shuraev

Investigating the effects of trendy ice baths, scientists at the University of Ottawa have made an interesting discovery on the beneficial way they affect cell functions, and have published their findings in Advanced Biology.

A new study conducted at the Human and Environmental Physiology Research lab (HEPRU) at the University of Ottawa has unveiled significant findings on the effects of cold water acclimation on autophagic (the cells’ recycling system, which promotes cellular health) and apoptotic (the programmed cell death that gets rid of damaged cells) responses in young males. The research highlights the potential for cold exposure to enhance cellular resilience against stress.

The study, conducted by Kelli King, postdoctoral fellow, and Glen Kenny, Full Professor at uOttawa’s School of Human Kinetics and Director of HEPRU, involved ten healthy young males who underwent cold-water immersion at 14°C for one hour across seven consecutive days. Blood samples were collected to analyse the participants’ cellular responses before and after the acclimation period.

“Our findings indicate that repeated cold exposure significantly improves autophagic function, a critical cellular protective mechanism,” says Professor Kenny. “This enhancement allows cells to better manage stress and could have important implications for health and longevity.”

The research revealed that while autophagy was initially dysfunctional after high-intensity cold stress, consistent exposure over a week led to increased autophagic activity and decreased cellular damage signals.

“By the end of the acclimation, we noted a marked improvement in the participants’ cellular cold tolerance,” explains King, the study’s first author. “This suggests that cold acclimation may help the body effectively cope with extreme environmental conditions.”

The implications of this study extend beyond athletic performance. Cold water immersion has gained popularity for its potential health benefits, and this research provides some scientific backing for its efficacy. The findings suggest that proper autophagic activity could not only extend cellular longevity but also prevent the onset of various diseases.

As the use of cold exposure becomes increasingly mainstream, understanding its effects on cellular mechanisms is vital. Professor Kenny emphasises, “This work underscores the importance of acclimation protocols in enhancing human health, especially in contexts where individuals are exposed to extreme temperatures.”

“We were amazed to see how quickly the body adapted,” notes King. “Cold exposure might help prevent diseases and potentially even slow down aging at a cellular level. It’s like a tune-up for your body’s microscopic machinery.”

These results apply to young males and more research is needed to see if it would also apply to other cohorts.

Source: University of Ottawa