Month: March 2025

Categories : Mental HealthTags :

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

Categories : CancerTags :

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 :

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 :

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 :

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

Categories : Antibiotics PaediatricsTags :

How Antibiotics in Infancy may Increase Diabetes Risk

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Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

Exposure to antibiotics during a key developmental window in infancy can stunt the growth of insulin-producing cells in the pancreas and may boost risk of diabetes later in life, new research in mice suggests. The study, published this month in the journal Science, also pinpoints specific microorganisms that may help those critical cells proliferate in early life.

The findings are the latest to shine a light on the importance of the human infant microbiome—the constellation of bacteria and fungi living on and in us during our first few years. The research could lead to new approaches for addressing a host of metabolic diseases.

“We hope our study provides more awareness for how important the infant microbiome actually is for shaping development,” said first author Jennifer Hill, assistant professor in molecular, cellular and developmental biology at CU’s BioFrontiers Institute. “This work also provides important new evidence that microbe-based approaches could someday be used to not only prevent but also reverse diabetes.”

Something in the environment

More than 2 million U.S. adults live with Type 1 diabetes. The disease typically emerges in childhood, and genetics play a strong role. But scientists have found that, while identical twins share DNA that predisposes them to Type 1 diabetes, only one twin usually gets the disease.

“This tells you that there’s something about their environmental experiences that is changing their susceptibility,” said Hill.

For years, she has looked to microbes for answers.

Previous studies show that children who are breastfed or born vaginally, which can both promote a healthy infant microbiome, are less likely to develop Type 1 diabetes than others. Some research also shows that giving babies antibiotics early can inadvertently kill good bugs with bad and boost diabetes risk.

The lingering questions: What microbes are these infants missing out on?

“Our study identifies a critical window in early life when specific microbes are necessary to promote pancreatic cell development,” said Hill.

A key window of opportunity

She explained that human babies are born with a small amount of pancreatic “beta cells,” the only cells in the body that produce insulin. But some time in a baby’s first year, a once-in-a-lifetime surge in beta cell growth occurs.

“If, for whatever reason, we don’t undergo this event of expansion and proliferation, that can be a cause of diabetes,” Hill said.

She conducted the current study as a postdoctoral researcher at the University of Utah with senior author June Round, a professor of pathology.

They found that when they gave broad-spectrum antibiotics to mice during a specific window (the human equivalent of about 7 to 12 months of life), the mice developed fewer insulin producing cells, higher blood sugar levels, lower insulin levels and generally worse metabolic function in adulthood.

“This, to me, was shocking and a bit scary,” said Round. “It showed how important the microbiota is during this very short early period of development.”

Lessons in baby poop

In other experiments, the scientists gave specific microbes to mice, and found that several they increased their production of beta cells and boosted insulin levels in the blood. The most powerful was a fungus called Candida dubliniensis.

The team used faecal samples from The Environmental Determinants of Diabetes in the Young (TEDDY) study to make what Hill calls “poop slushies” and fed them to the mice.

When the researchers inoculated newborn mice with poop from healthy infants between 7 to 12 months in age, their beta cells began to grow. Poop from infants of other ages did not do the same. Notably, Candida dublineinsis was abundant in human babies only during this time period.

“This suggests that humans also have a narrow window of colonisation by these beta cell promoting microbes,” said Hill.

When male mice that were genetically predisposed to Type 1 diabetes were colonised with the fungus in infancy, they developed diabetes less than 15% of the time. Males that didn’t receive the fungus got diabetes 90% of the time.

Even more promising, when researchers gave the fungus to adult mice whose insulin-producing cells had been killed off, those cells regenerated.

Too early for treatments

Hill stresses that she is not “anti-antibiotics.” But she does imagine a day when doctors could give microbe-based drugs or supplements alongside antibiotics to replace the metabolism-supporting bugs they inadvertently kill.

Poop slushies (faecal microbiota transplants) have already been used experimentally to try to improve metabolic profiles of people with Type 2 diabetes, which can also damage pancreatic beta cells.

But such approaches can come with real risk, since many microbes that are beneficial in childhood can cause harm in adults. Instead, she hopes that scientists can someday harness the specific mechanisms the microbes use to develop novel treatments for healing a damaged pancreas—reversing diabetes.

She recently helped establish a state-of-the-art “germ-free” facility for studying the infant microbiome at CU Boulder. There, animals can be bred and raised entirely without microbes, and by re-introducing them one by one scientists can learn they work.

“Historically we have interpreted germs as something we want to avoid, but we probably have way more beneficial microbes than pathogens,” she said. “By harnessing their power, we can do a lot to benefit human health.”

Source: University of Colorado at Boulder

Categories : Mental HealthTags :

Social Skills not as Relevant for Autism Diagnosis than Thought

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Photo by Peter Burdon on Unsplash

People with autism are typically diagnosed by clinical observation and assessment. To deconstruct the clinical decision process, which is often subjective and difficult to describe, researchers used a large language model (LLM) to synthesize the behaviours and observations that are most indicative of an autism diagnosis. Their results, publishing in the Cell Press journal Cell, show that repetitive behaviours, special interests, and perception-based behaviours are most associated with an autism diagnosis.

These findings have potential to improve diagnostic guidelines for autism by decreasing the focus on social factors – which the established guidelines in the DSM-5 focus on but the model did not classify among the most relevant in diagnosing autism.

“Our goal was not to suggest that we could replace clinicians with AI tools for diagnosis,” says senior author Danilo Bzdok of the Mila Québec Artificial Intelligence Institute and McGill University in Montreal. “Rather, we sought to quantitatively define exactly what aspects of observed behaviour or patient history a clinician uses to reach a final diagnostic determination. In doing so, we hope to empower clinicians to work with diagnostic instruments that are more in line with their empirical realities.”

The scientists leveraged a transformer language model, which was pre-trained on about 489 million unique sentences. They then fine-tuned the LLM to predict the diagnostic outcome from a collection of more than 4000 reports written by clinicians working with patients considered for autism diagnosis. The reports, which were often used by multiple clinicians, included accounts of observed behaviour and relevant patient history but did not include a suggested diagnostic outcome.

The team developed a bespoke LLM module that pinpointed specific sentences in the reports that were most relevant to a correct diagnosis prediction. They then extracted the numerical representation of these highly autism-relevant sentences and compared them directly with the established diagnostic criteria enumerated in the DSM-5.

“Modern LLMs, with their advanced natural language processing capabilities, are natively suited to this textual analysis,” Bzdok says. “The key challenge we faced was in designing sentence-level interpretability tools to pinpoint the exact sentences, expressed by the healthcare professional themselves, that were most essential to a correct diagnosis prediction by the LLM.”

The researchers were surprised by how clearly the LLM was able to distinguish between the most diagnostically relevant criteria. For example, their framework flagged that repetitive behaviours, special interests, and perception-based behaviour were the criteria most relevant to autism. While these criteria are used in clinical settings, current criteria focus more on deficits in social interplay and lack of communication skills.

The authors note that there are limitations to this study, including a lack of geographical diversity. Additionally, the researchers did not analyse their results based on demographic variables, with the goal of making the conclusions more broadly applicable.

The team expects their framework will be helpful to researchers and medical professionals working with a range of psychiatric, mental health, and neurodevelopmental disorders in which clinical judgement forms the bulk of the diagnostic decision-making process.

“We expect this paper to be highly relevant to the broader autism community,” Bzdok says. “We hope that our paper motivates conversations about grounding diagnostic standards in more empirically derived criteria. We also hope it will establish common threads that link seemingly diverse clinical presentations of autism together.”

Source: ScienceDaily

Categories : Diet and NutritionTags :

Why Does Obesity Takes Away the Pleasure of Eating?

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Photo by Jonathan Borba

The pleasure we get from eating junk food — the dopamine rush from crunching down on salty, greasy chips and a luscious burger — is often blamed as the cause of overeating and rising obesity rates in our society. But a new study suggests that pleasure in eating, even eating junk food, is key for maintaining a healthy weight in a society that abounds with cheap, high-fat food.

Paradoxically, anecdotal evidence suggests that people with obesity may take less pleasure in eating than those of normal weight. Brain scans of obese individuals show reduced activity in pleasure-related brain regions when presented with food, a pattern also observed in animal studies.

Now, University of California, Berkeley, researchers have identified a possible underlying cause of this phenomenon — a decline in neurotensin, a brain peptide that interacts with the dopamine network — and a potential strategy to restore pleasure in eating in a way that helps reduce overall consumption.

The study, published in Nature, reveals an unsuspected brain mechanism that explains why a chronic high-fat diet can reduce the desire for high-fat, sugary foods, even when these foods remain easily accessible. The researchers propose that this lack of desire in obese individuals is due to a loss of pleasure in eating caused by long-term consumption of high-calorie foods. Losing this pleasure may actually contribute to the progression of obesity.

“A natural inclination toward junk food is not inherently bad — but losing it could further exacerbate obesity,” said Stephan Lammel, a UC Berkeley professor in the Department of Neuroscience and a member of the Helen Wills Neuroscience Institute.

The researchers found that this effect is driven by a reduction in neurotensin in a specific brain region that connects to the dopamine network. Importantly, they demonstrate that restoring neurotensin levels — either through dietary changes or genetic manipulations that enhance neurotensin production — can reinstate the pleasure in eating and promote weight loss.

“A high-fat diet changes the brain, leading to lower neurotensin levels, which in turn alters how we eat and respond to these foods,” Lammel said. “We found a way to restore the desire for high-calorie foods, which may actually help with weight management.”

While findings in mice don’t always translate directly to humans, this discovery could open new avenues for addressing obesity by restoring food-related pleasure and breaking unhealthy eating patterns.

“Imagine eating an amazing dessert at a great restaurant in Paris — you experience a burst of dopamine and happiness,” said Neta Gazit Shimoni, a UC Berkeley postdoctoral fellow. “We found that this same feeling occurs in mice on a normal diet, but is missing in those on a high-fat diet. They may keep eating out of habit or boredom, rather than genuine enjoyment.”

Gazit Shimoni and former UC Berkeley graduate student Amanda Tose are co-first authors, and Lammel is senior author of the study, which will be published March 26 in the journal Nature.

Solving a long-standing puzzle in obesity research

For decades, doctors and researchers have struggled to understand and treat obesity, as countless fad diets and eating regimens have failed to produce long-term results. The recent success of GLP-1 agonists like Ozempic, which curb appetite by increasing feelings of fullness, stands out among many failed approaches.

Lammel studies brain circuits, particularly the dopamine network, which plays a crucial role in reward and motivation. Dopamine is often associated with pleasure, reinforcing our desire to seek rewarding experiences, such as consuming high-calorie foods.

While raising mice on a high-fat diet, Gazit Shimoni noticed a striking paradox: While in their home cages, these mice strongly preferred high-fat chow, which contained 60% fat, over normal chow with only 4% fat, leading them to gain excessive weight. However, when they were taken out of their home cages and given free access to high-calorie treats such as butter, peanut butter, jelly or chocolate, they showed much less desire to indulge than normal-diet mice, which immediately ate everything they were offered.

“If you give a normal, regular-diet mouse the chance, they will immediately eat these foods,” Gazit Shimoni said. “We only see this paradoxical attenuation of feeding motivation happening in mice on a high-fat diet.”

She discovered that this effect had been reported in past studies, but no one had followed up to find out why, and how the effect connects to the obesity phenotype observed in these mice.

Restoring neurotensin reverses obesity-related brain changes

To investigate this phenomenon, Lammel and his team used optogenetics, a technique that allows scientists to control brain circuits with light. They found that in normal-diet mice, stimulating a brain circuit that connects to the dopamine network increased their desire to eat high-calorie foods, but in obese mice, the same stimulation had no effect, suggesting that something must have changed.

The reason, they discovered, was that neurotensin was reduced so much in obese mice that it prevented dopamine from triggering the usual pleasure response to high-calorie foods.

“Neurotensin is this missing link,” Lammel said. “Normally, it enhances dopamine activity to drive reward and motivation. But in high-fat diet mice, neurotensin is downregulated, and they lose the strong desire to consume high-calorie foods — even when easily available.”

The researchers then tested ways to restore neurotensin levels. When obese mice were switched back to a normal diet for two weeks, their neurotensin levels returned to normal, dopamine function was restored, and they regained interest in high-calorie foods.

When neurotensin levels were artificially restored using a genetic approach, the mice not only lost weight, but also showed reduced anxiety and improved mobility. Their feeding behaviour also normalised, with increased motivation for high-calorie foods and a simultaneous reduction of their total food consumption in their home cages.

“Bringing back neurotensin seems to be very, very critical for preventing the loss of desire to consume high-calorie foods,” Lammel said. “It doesn’t make you immune to getting obese again, but it would help to control eating behaviour, to bring it back to normal.”

Toward more precise treatments for obesity

Although directly administering neurotensin could theoretically restore feeding motivation in obese individuals, neurotensin acts on many brain areas, raising the risk of unwanted side effects. To overcome this, the researchers used gene sequencing, a technique that allowed them to identify specific genes and molecular pathways that regulate neurotensin function in obese mice.

This discovery provides crucial molecular targets for future obesity treatments, paving the way for more precise therapies that could selectively enhance neurotensin function without broad systemic effects.

“We now have the full genetic profile of these neurons and how they change with high-fat diets,” Lammel said. “The next step is to explore pathways upstream and downstream of neurotensin to find precise therapeutic targets.”

Lammel and Gazit Shimoni plan to expand their research to explore neurotensin’s role beyond obesity, investigating its involvement in diabetes and eating disorders.

“The bigger question is whether these systems interact across different conditions,” Gazit Shimoni said. “How does starvation affect dopamine circuits? What happens in eating disorders? These are the questions we’re looking at next.”

Source: University of California – Berkeley

Categories : Cardiovascular DiseaseTags :

Possible Link Between Medication and Unexpected Blood Clots

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Thrombophilia. Credit: Scientific Animations CC4.0.

Why do medications that are supposed to help patients with chronic inflammatory diseases sometimes lead to blood clots? This is one of the questions that a team of researchers from Aarhus University has sought to answer in a study that has just been published in the journal Inflammopharmacology.

The study suggests that disturbances in the JAK-STAT signalling pathway, an important communication pathway in the body, may contribute to this side effect.

“In the study, we uncover the potential links between components of the JAK-STAK signalling pathway, blood markers in patients with blood clots, and the genetic factors that contribute to the risk of blood clots in patients. This helps improve our understanding of why we see an increased risk of blood clots when using JAK inhibitors,” explains Stine Rabech Haysen, former medical student at the Department of Biomedicine at Aarhus University, who is the first author of the publication. 

The potential of the study

In the study, researchers used publicly available data from a number of published studies about patients with blood clots and compared them with a healthy control group.

They found no direct genetic explanation, but they did find a statistically significant enrichment of genes that are subject to regulatory control of the JAK-STAT signalling pathway among genes whose expression is altered in patients with blood clots.

“Although we cannot draw definitive conclusions about the mechanistic link between the use of JAK inhibitors and the risk of blood clots, our study demonstrates the potential of using data mining to identify and shed light on possible mechanisms of drug side effects,” says one of the study’s senior authors, associate professor at the Department of Biomedicine Per Qvist.

What does this mean for patients?

Although JAK inhibitors rarely lead to blood clots, it’s important to understand the mechanism behind them so that the risk can be reduced.

“For the average person, our study means that we’re getting closer to understanding why some drugs can have dangerous side effects like blood clots. And going forward, our method could help identify and prevent serious side effects, potentially making drug treatment safer,” explains the other senior author of the study, associate professor at the Department of Biomedicine Tue Wenzel Kragstrup.

The researchers will now test the method on other types of medication to see if it can be used to detect side effects more widely.

Source: Aarhus University

Categories : New Compounds and TreatmentsTags :

New Cannabis Formula will Help Epilepsy, Multiple Sclerosis Sufferers

On By ModernMedia
Photo by Kindel Media on Unsplash

Scientists at the University of South Australia have come up with an innovative solution to improve the effectiveness of cannabidiol to treat epilepsy, multiple sclerosis and other neurodegenerative diseases.

Cannabidiol (CBD), a non-psychoactive cannabis compound, is widely prescribed for its analgesic, anti-inflammatory and neuroprotective properties, but its clinical applications to date have been limited by its poor water solubility and absorption in the human body.

By developing a phospholipid complex – a class of lipids (fats) that contain phosphorus – UniSA researchers have increased the solubility of cannabidiol by up to six times and improved its absorption in the gastrointestinal tract.

Lead researcher Professor Sanjay Garg says the breakthrough, reported in the International Journal of Molecular Sciences, means that patients could experience more consistent and effective results with lower doses of oral CBD medications.

Currently, only a small fraction of orally ingested CBD reaches the bloodstream, limiting its therapeutic effects.

“For this reason, a number of different formulations have been explored, including the production of synthetic CBD, self-emulsifying delivery systems, and encapsulating CBD in gelatine matrix pellets, but all of them have only resulted in minor improvements in bioavailability,” Prof Garg says.

His research team identified the optimal phospholipid composition to form nanosized CBD-PLC particles. Compared to pure CBD, the phospholipid complex improved dissolution rates from 0% to 67.1% within three hours, demonstrating a significant enhancement in drug release.

In cellular uptake studies, CBD-PLC exhibited 32.7% higher permeability than unmodified CBD, ensuring greater absorption through the intestinal wall.

Another critical advantage of this new delivery system is its stability. Traditional CBD formulations degrade over time when exposed to heat, light or oxygen, reducing potency and shelf life.

However, testing over 12 months showed that CBD-PLC retained its performance under varied storage conditions, making it a more reliable option for pharmaceutical applications.

The study’s first author, UniSA PhD candidate Thabata Muta, says the discovery has significant implications for the future of CBD-based therapeutics.

“Improved bioavailability means that lower doses can achieve the same therapeutic effect, potentially reducing side effects and making treatment more cost effective,” Thabata says.

The research team believes that this innovation could be applied beyond CBD, providing a blueprint for enhancing the absorption of other poorly water-soluble drugs.

With the global CBD market projected to grow from USD 7.59 billion in 2023 to USD 202.45 billion by 2032, the findings of this study come at a crucial time, according to the study authors.

The team is now exploring opportunities for commercialisation and clinical trials to validate their new formulation.

Source: University of South Australia