Tag: 8/4/25

Categories : Cardiovascular Disease Mental HealthTags :

New Study Investigates Effects of ADHD Medications on the Heart

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Photo by Annie Spratt on Unsplash

A new study led by the University of Southampton has found that medications for ADHD have overall small effects on blood pressure and heart rate after weeks or a few months of use.

There have been concerns about the side effects of ADHD medications but the new findings, coupled with other studies, suggest that the benefits of taking these medications outweigh the risks, while highlighting the need for careful monitoring.

The study, published in The Lancet Psychiatry, conducted the largest and most comprehensive analysis of the cardiovascular effects of ADHD medications based on the results of randomised controlled trials – the most rigorous type of clinical study to assess medication effects.

Professor Samuele Cortese, senior lead author of the study from the University of Southampton said: “When it comes to taking any medication, risks and benefits should always be assessed together. We found an overall small increase in blood pressure and pulse for the majority of children taking ADHD medications.

“Other studies show clear benefits in terms of reductions in mortality risk and improvement in academic functions, as well as a small increased risk of hypertension, but not other cardiovascular diseases. Overall, the risk-benefit ratio is reassuring for people taking ADHD medications.”

The study was funded by the National Institute for Health and Care Research (NIHR), within the framework of the NIHR Research Professorships scheme to Professor Samuele Cortese, with Dr Luis Farhat (University of São Paulo, Brazil) as first author and Professor Alexis Revet (University of Toulouse, France) as co-senior author.

It is estimated that attention-deficit/hyperactivity disorder (ADHD) affects around 4 per cent of children in the UK. Of these, around 45 per cent are treated with medication.

The international team of investigators analysed data from 102 randomized controlled trials, including a total of 22,702 participants with ADHD. They used an advanced statistical approach – network meta-analysis – that allowed them to compare the effects of several medications, even when the medications were not directly compared in the trials included in the analysis.

They found that all ADHD medications were generally associated with overall small effects on blood pressure, heart rate, and ECG parameters. With the exception of guanfacine (which leads to decreased blood pressure and heart rate), other medications led to increases in the values of these parameters.

No significant differences were found between stimulants (including methylphenidate and amphetamine) and non-stimulants (atomoxetine and viloxazine) with regard to their effects on blood pressure and heart rate.

“Our findings should inform future clinical guidelines, stressing the need to systematically monitor blood pressure and heart rate, both for stimulants and non-stimulants. This should be particularly relevant for practitioners who might assume that only stimulants have a negative effect on the cardiovascular system,” said Dr Farhat.

The researchers say that those with existing heart conditions should discuss the side effects of ADHD medications with a specialist cardiologist before starting treatment.

Professor Revet added: “Our findings, based on randomised controlled trials that tend to be of short duration due to ethical issues, should be complemented by results from real-world, longer-term studies.”

The research team will now look to see if some groups might be more vulnerable to cardiovascular side effects than others.

NIHR Research Professor Cortese concluded: “While our findings are informative at the group level, that is, on average, we cannot exclude that a subgroup of individuals may have a higher risk of more substantial cardiovascular alterations.

“While it is currently not possible to identify those individuals at higher risk, efforts based on precision medicine approaches will hopefully provide important insights in the future.”

Source: University of Southampton

Categories : Respiratory DiseasesTags :

A Gentle Approach Offers New Hope for Inflammatory Lung Diseases

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A collection of immune cells known as a granuloma that results from chronic inflammation in the interstitial lung disease sarcoidosis. White dots indicate the receptor NRP2, which is overexpressed in response to inflammation. Credit: Scripps Research

Pulmonary sarcoidosis is a lung disease characterised by granulomas—tiny clumps of immune cells that form in response to inflammation. It’s the most inflammatory of the interstitial lung diseases (ILDs), a family of conditions that all involve some level of inflammation and fibrosis, or scarring, of the lungs. In the U.S., pulmonary sarcoidosis affects around 200 000 patients. The cause is unknown, and no new treatments have been introduced in the past 70 years. 

In a paper published in Science Translational Medicine, scientists at Scripps Research and aTyr Pharma characterised a protein, HARSWHEP, that can soothe the inflammation associated with sarcoidosis by regulating white blood cells. Reducing inflammation slows the disease’s progression and results in less scarring. A phase 1b/2a clinical trial of efzofitimod, a therapeutic form of HARSWHEP, showed promising results.

“Taken together, these results validate a new way to approach immune regulation in chronic lung disease,” says Paul Schimmel, professor of molecular medicine and chemistry at Scripps Research and the study’s senior author.

The drug’s power lies in its gentle nature. “It’s not a hammer; it’s not overly suppressing the immune system. It’s just nudging the immune system in a certain way,” explains Leslie A. Nangle, Vice President of Research at aTyr Pharma and the paper’s first author. “And if you can quiet the inflammation, you can stop the cycle of ongoing fibrosis.”

HARSWHEP is part of an ancient class of proteins known as aminoacyl-tRNA synthetases (aaRSs). Typically, aaRSs play a key role in protein synthesis. “They’re in every cell in your body. They’re in every organism on the planet,” Nangle says. Over time, new versions known as splice variants have emerged that bind to receptors on the outsides of cells and initiate different events throughout the body.

One such variant, HARSWHEP, entered the picture about 525 million years ago. Nangle and Schimmel screened more than 4,500 receptors and were surprised to find that HARSWHEP will bind only to the receptor neuropilin-2 (NRP2). This receptor is known for its role in development of the lymphatic system—the circulatory system through which immune cells travel—not immune function. But the researchers found that when small, circulating white blood cells known as monocytes enter a tissue in response to inflammation and develop into larger, more specialized white blood cells known as macrophages, those cells start to express high levels of NRP2.

“We had a protein with an unknown function. We had a receptor that was doing something on immune cells that had never been characterized. So we had a couple things we had to match up,” Nangle says.

The team found that HARSWHEP binding to NRP2 physically transforms the macrophage. “It’s creating a new type of macrophage that is less inflammatory and actually helps to resolve inflammation,” Nangle explains.

To characterise HARSWHEP’s mechanism of action, the team administered the protein in mice and rats and found that it reduced lung inflammation and the progression of fibrosis.

In separately published clinical trial data, the team saw a positive impact on patients who were treated with efzofitimod while tapering off of oral corticosteroids. Long-term steroid treatment, currently the first-line option, is associated with significant weight gain and organ damage, and the immunosuppressive effects leave patients vulnerable to infection.

The team also characterised patients’ circulating immune cells before and after efzofitimod treatment. They saw that it reduced key indicators of the inflammation that drives sarcoidosis, such as the concentration of macrophages and other inflammatory immune cells.

While they’re exploring sarcoidosis first, efzofitimod is a potential treatment for many interstitial lung diseases, Nangle explains. The aTyr team plans to explore treating other ILDs and is running a clinical trial now for scleroderma-related ILD.

The work highlights macrophages as a possible target for treating ILDs, and the promise of HARSWHEP could foretell other aaRSs’ therapeutic potential.

Nangle describes this work as moving “from concept to clinic.” Schimmel has worked on aaRSs throughout his tenure at Scripps Research. aTyr Pharma spun out of Schimmel’s lab; his former graduate student Nangle was the company’s first employee upon opening their labs in 2006.

“Original work that happened at Scripps gave rise to the idea that this could be a new class of therapeutic molecules, Nangle says. “We have now moved it all the way to clinical development. It’s a proof of concept for this whole class of molecules and the work Paul has done.”

Source: Scripps Research Institute

Categories : Neurology PaediatricsTags :

Childhood Experiences Shape White Matter with Cognitive Effects Seen Years Later

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Photo by Caleb Woods on Unsplash

Mass General Brigham investigators have linked difficult early life experiences with reduced quality and quantity of the white matter communication highways throughout the adolescent brain. This reduced connectivity is also associated with lower performance on cognitive tasks. However, certain social resiliency factors like neighbourhood cohesion and positive parenting may have a protective effect. Results are published in Proceedings of the National Academy of Sciences (PNAS).

White matter are the communication highways that allow the brain networks to carry out the necessary functions for cognition and behaviour. They develop over the course of childhood, and childhood experiences may drive individual differences in how white matter matures. Lead author Sofia Carozza, PhD, and senior author Amar Dhand, MD, PhD, of the Department of Neurology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, wanted to understand what role this process plays in cognition once children reach adolescence.

“The aspects of white matter that show a relationship with our early life environment are much more pervasive throughout the brain than we’d thought. Instead of being just one or two tracts that are important for cognition, the whole brain is related to the adversities that someone might experience early in life,” said Carozza.

The team studied data from 9082 children (about half of them girls, with an average age of 9.5) collected in the Adolescent Brain Cognitive Development (ABCD) study. This study, funded by the National Institutes of Health and conducted at 21 centres across the U.S., gathered information on brain activity and structure, cognitive abilities, environment, mood and mental health. The researchers looked at several categories of early environmental factors, including prenatal risk factors, interpersonal adversity, household economic deprivation, neighbourhood adversity, and social resiliency factors.

Carozza and Dhand used diffusion imaging scanning of the brain to measure fractional anisotropy (FA)—a way of estimating the integrity of the white matter connections—and streamline count, an estimate of their strength. They then used a computational model to compare how these features of white matter were related to both childhood environmental factors and current cognitive abilities such as language skills and mental arithmetic.

Their analysis revealed widespread differences in white matter connections throughout the brain depending on the children’s early-life environments. In particular, the researchers found lower quality of white matter connections in parts of the brain tied to mental arithmetic and receptive language. These white matter differences accounted for some of the relationship between adverse life experiences in early childhood and lower cognitive performance in adolescence.

“We are all embedded in an environment, and features of that environment such as our relationships, home life, neighbourhood, or material circumstances can shape how our brains and bodies grow, which in turn affects what we can do with them,” said Carozza. “We should work to make sure that more people can have those stable, healthy home lives that the brain expects, especially in childhood.”

The researchers note that their study is based on observational data, which means they cannot draw strong causal conclusions. Brain imaging was also only available at a single timepoint, offering a snapshot but not allowing researchers to track changes over time. Prospective studies—following children over time and collecting brain imaging information at multiple time points—would be needed to more definitively connect adversity and cognitive performance.

Source: Mass General Brigham

Categories : Immune SystemTags :

Findings on T Cell Exhaustion: The Body Prepares Early for a Long Fight

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Scanning electron micrograph of a T cell lymphocyte. Credit: NIH / NIAID

When an infection is prolonged and severe, T cell exhaustion comes into play to prevent to reign in the immune system and prevent damage to the body. A study published in Nature reveals that right from the beginning of mild illness, the body also produces these special T cells previously known only from chronic, severe infections and tumours.

There are different types of T cells in the body, all of which play a crucial role in the immune system. They fight pathogens and control the immune response. However, some subtypes become less effective or even cease their activity altogether as the disease progresses. This has a protective function: in persisting infections, it would harm the body if the immune system continued to fight the pathogens aggressively. But in cancer treatment, T cell exhaustion means that therapeutic measures may no longer be effective.

Until now, it was assumed that the body only produces such T cells in severe and persisting infections. The results of the researchers, from Helmholtz Munich and the Technical University of Munich, show that this is not the case. “We were able to show that the body prepares T cell subtypes that are predisposed to exhaustion even in early infection phases of moderate diseases,” says Dietmar Zehn, Professor of Animal Physiology and Immunology at TUM and last study author.

Different T Cells for Different Purposes

The team deduces from the discovery that the body assembles a range of different T cells early on at the onset of the disease to arm itself for different disease progressions. Depending on the course of the disease, it then has cells at its disposal to make the immune response more aggressive or more gentle — and in some circumstances, even to abort it.

“Our results expand the classic idea of the development of T cell exhaustion,” says Dietmar Zehn. “We therefore assume that our observations will help to further decipher the mechanisms behind T cell exhaustion.” A better understanding of these processes could help in the future to control the immune response in a targeted manner — for example, to strengthen the immune system in cancer patients or to weaken excessive defences, as is typical in severe cases of COVID-19, for instance.

Source: Technical University of Munich (TUM)