Tag: 29/1/25

Categories : Mental Health Metabolic DisordersTags : Leave a comment

What’s the Mechanism behind Behavioural Side Effects of GLP1RAs?

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Photo by I Yunmai on Unsplash

Glucagon-like peptide 1 receptor agonists (GLP1RA) – medications for type 2 diabetes and obesity that have recently been making headlines due to a rise in popularity as weight loss agents – have been linked with behavioural side effects. A large population-based analysis in Diabetes, Obesity and Metabolism assessed whether certain genetic variants might help explain these effects.

GLP1RA mimic the GLP-1 hormone in the body that helps control insulin and blood glucose levels and promotes feelings of satiety. GLP-1 binds to GLP1R on cells in the brain and pancreas.

Observational and epidemiological studies have shown that there may be neutral or protective effects of GLP1RAs on mental health symptoms. However, a study based on individuals taking GLP1RA suggests there is increased prescription of anti-depressants when used for treatment of diabetes. Early evidence in animal models suggest GLP1RA may decrease depressive and anxious symptoms, potentially presenting new treatment pathways; however, comparing these studies to human clinical evidence will not be possible for some time.

For the analysis, investigators examined common genetic variants in the GLP1R gene in 408 774 white British, 50 314 white European, 7 667 South Asian, 10 437 multiple ancestry, and 7641 African-Caribbean individuals.

Variants in the GLP1R gene had consistent associations with cardiometabolic traits (body mass index, blood pressure, and type 2 diabetes) across ancestries. GLP1R variants were also linked with risk-taking behavior, mood instability, chronic pain, and anxiety in most ancestries, but the results were less consistent. The genetic variants influencing cardiometabolic traits were separate from those influencing behavioral changes and separate from those influencing expression levels of the GLP1R gene.

The findings suggest that any observed behavioral changes with GLP1RA are likely not acting directly through GLP1R.

“Whilst it is not possible to directly compare genetic findings to the effects of a drug, our results suggest that behavioural changes are unlikely to be a direct result of the GLPRAs. Exactly how these indirect effects are occurring is currently unclear,” said corresponding author Rona J. Strawbridge, PhD, of the University of Glasgow, in the UK.

Source: Wiley

Categories : Mental Health NeurologyTags : Leave a comment

Elevated Opioid Neurotransmitter Activity Seen in Patients with Anorexia

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Photo from Freepik.

A study conducted at Turku PET Centre in Finland and published in showed that changes in the functioning of opioid neurotransmitters in the brain may underlie anorexia.

Anorexia nervosa is a serious psychiatric disorder characterised by restricted eating, fear of gaining weight, and body image disturbances, which may lead to severe malnutrition, depression and anxiety. This new study from Turku PET Centre, published in Molecular Psychiatry, shows how changes in neurotransmitter function in the brain may underlie anorexia.

“Opioid neurotransmission regulates appetite and pleasure in the brain. In patients with anorexia nervosa, the brain’s opioidergic tone was elevated in comparison with healthy control subjects. Previously we have shown that in obese patients the activity of the tone of this system is lowered. It is likely that the actions of these molecules regulate both the loss and increase in appetite,” says Professor Pirjo Nuutila from the University of Turku.

Number of opioid receptors in the brain (top row) and sugar intake (bottom row) in patients with anorexia nervosa. Credit: University of Turku

In addition, the researchers measured the brain’s glucose uptake. The brain accounts for about 20% of the body’s total energy consumption, so the researchers were interested in how a reduction in the energy intake affects the brain’s energy balance in anorexia.

“The brains of patients with anorexia nervosa used a similar amount of glucose as the brains of the healthy control subjects. Although being underweight burdens physiology in many ways, the brain tries to protect itself and maintain its ability to function for as long as possible,” says Professor Lauri Nummenmaa from Turku PET Centre and continues:

“The brain regulates appetite and feeding, and changes in brain function are associated with both obesity and low body weight. Since changes in opioid activity in the brain are also connected to anxiety and depression, our findings may explain the emotional symptoms and mood changes associated with anorexia nervosa.”

Source: University of Turku

Categories : COVIDTags : Leave a comment

Study Tracks Physical and Cognitive Impairments Associated with Long COVID

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Researchers following nearly 1000 people with post-COVID-19 syndrome found few changes to their symptoms in the second year of illness

Photo by Usman Yousaf on Unsplash

Two-thirds of people with post-COVID-19 syndrome have persistent, objective symptoms – including reduced physical exercise capacity and reduced cognitive test performances – for a year or more, with no major changes in symptom clusters during the second year of their illness, according to a new study published January 23rd in the open-access journal PLOS Medicine by Winfried Kern of Freiburg University, Germany, and colleagues.

Self-reported health problems following SARS-CoV-2 infection have commonly been described and may persist for months. However, the long-term prognosis of post-COVID-19 syndrome (PCS) is unknown.

In the new study, researchers studied 982 people aged 18 to 65 who had previously been identified as having PCS, as well as 576 controls. All participants visited one of several university health centers in southwestern Germany for comprehensive assessments, including neurocognitive, cardiopulmonary exercise, and laboratory testing.

The predominant symptom clusters among people with PCS were fatigue/exhaustion, neurocognitive disturbances, chest symptoms/breathlessness, and anxiety/depression/sleep problems. Nearly 68% of people who originally reported PCS still struggled with symptoms in the second year. Exercise intolerance with post-exertional malaise was reported by 35.6% of people with persistent PCS, and these people had worse outcomes and more severe symptoms. People with lower educational attainment, obesity, or more severe illness during the initial COVID-19 infection were also at higher risk of prolonged symptoms.

When they looked at objective measures of health and cognition, the team found that people with persistent PCS had significant reductions in handgrip strength, maximal oxygen consumption, and ventilatory efficiency. Patients with persistent PCS and post-exertional malaise scored lower than control patients on cognitive tests measuring memory, attention, and processing speed; however, the researchers point out that they had no data on cognition before acute COVID-19 infection. The team was not able to identify differences in cardiac function or laboratory values, including tests of viral persistence.

“The results call for the inclusion of cognitive and exercise testing in the clinical evaluation and monitoring of patients with suspected PCS,” the authors say. “Observational studies with longer follow-up are urgently needed to evaluate factors for improvement and non-recovery from PCS.”

The authors add, “Grave symptoms with mental and physical exercise dysfunction, but no laboratory markers in Long Covid/post-Covid syndrome.”

Provided by PLOS

Categories : Diseases, Syndromes and Conditions PaediatricsTags : Leave a comment

High Uric Acid Levels Linked to Mortality in Children with Severe Malaria

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Red Blood Cell Infected with Malaria Parasites Colourised scanning electron micrograph of red blood cell infected with malaria parasites (teal). The small bumps on the infected cell show how the parasite remodels its host cell by forming protrusions called ‘knobs’ on the surface, enabling it to avoid destruction and cause inflammation. Uninfected cells (red) have smoother surfaces. Credit: NIAID

Indiana University School of Medicine researchers and their collaborators in Uganda at the Makerere University School of Medicine have uncovered a significant connection between elevated uric acid levels and life-threatening outcomes in children with severe malaria.

Published in Nature Medicine, the study identified hyperuricaemia – high uric acid levels – as a potential contributor to increased mortality and long-term neurodevelopmental challenges in children with severe malaria. These findings open the door to future research that could improve treatment strategies for children affected by severe malaria, a disease caused by mosquito-transmitted parasites and a leading cause of death in African children.

“Our findings show that hyperuricemia is strongly associated with death in the hospital and after discharge and with long-term cognitive impairment in children with severe malaria,” said Chandy C. John, MD, paediatrics professor at IU School of Medicine, who co-led the study. “We also showed several mechanisms by which hyperuricaemia may lead to these outcomes, suggesting that hyperuricaemia is not just associated with bad outcomes but may contribute to them.”  

The researchers analysed data from two independent groups of children with severe malaria in Uganda and found that 25% had hyperuricaemia. This condition is caused by excess uric acid, which is a harmful body waste substance found in blood. The primary drivers of hyperuricaemia in study participants were broken-down infected red blood cells and kidney injury, which reduces the body’s ability to get rid of the extra uric acid. 

In the study, hyperuricemia was linked to four negative outcomes in children with severe malaria: serious health complications like coma and anaemia, a higher risk of death during hospitalisation, a higher risk of death after discharge from the hospital, and long-term cognitive impairment in survivors.  

The study also revealed that children with hyperuricemia had more harmful gut bacteria, which can cross the injured gut lining and cause sepsis. Together, these findings highlight a need for clinical trials to test the effectiveness of uric acid-lowering medications as an additional treatment for severe malaria. 

“Additional studies are needed to determine whether lowering uric acid in children with severe malaria might reduce hospital deaths, post-discharge deaths and long-term cognitive impairment,” said Andrea Conroy, PhD, associate professor of paediatrics at the IU School of Medicine and co-leader of the study. “Our hope is that these studies will provide new insights and potentially lead to improved treatments that save lives.” 

This research builds on the team’s recent discovery of partial resistance to the primary treatment for malaria in African children with severe malaria. Both studies underscore the importance of prioritizing new strategies to combat malaria, which affected 263 million people and caused nearly 600,000 deaths worldwide in 2023.

Source: Indiana University

Categories : NeurologyTags : Leave a comment

Nerve Stimulation Fails When the Brain is not ‘Listening’

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A small device worn on the body can stimulate the nervous system via electrodes on the ear. Credit: Vienna University of Technology.

Various diseases can be treated by stimulating the vagus nerve in the ear with electrical signals, but the results can be ‘hit or miss’. A study recently published in Frontiers in Physiology has now shown that the electrical signals must be synchronised with the body’s natural rhythms – heartbeat and breathing.

Some health problems, from chronic pain and inflammation to neurological diseases, can also be treated by nerve stimulation, for example with the help of electrodes that are attached to the ear and activate the vagus nerve. This method is sometimes referred to as an ‘electric pill’.

However, vagus nerve stimulation does not always work the way it is supposed to. A study conducted by TU Wien (Vienna) in cooperation with the Vienna Private Clinic now shows how this can be improved: Experiments demonstrate that the effect is very good when the electrical stimulation is synchronised with the body’s natural rhythms – the actual heartbeat and breathing.

The ‘electric pill’ for the parasympathetic nervous system

The vagus nerve plays an important role in our body: it is the longest nerve of the parasympathetic nervous system, the part of the nervous system that is significantly involved in the precise control of the internal organs and blood circulation, and is responsible for recovery and building up the body’s own reserves. A branch of the vagus nerve also leads from the brain directly into the ear, which is why small electrodes in the ear can be used to activate the vagus nerve, stimulate the brain and thus influence various functions of the body.

“However, it turns out that this stimulation does not always produce the expected results,” says Prof Eugenijus Kaniusas from the Institute of Biomedical Electronics at TU Wien. “The electrical stimulation does not have an effect on the nervous system at all times. You could say that the brain is just not always listening. It’s as if there is a gate to the control centre of the nervous system that is sometimes open and then closed again, and this can change in less than a second.”

Five people have now been examined in a pilot study. Their vagus nerve was electrically activated to lower their heart rate. It is already known from previous studies that heart rate is a potential indicator of whether stimulation therapy is beneficial or not.

It was shown that the temporal connection between the stimulation and the heartbeat plays a decisive role. If the vagus nerve is stimulated at a rhythm that is not synchronised with the heartbeat, hardly any effect can be observed. However, if the stimulation signals are always applied when the heart is contracting (during systole), a strong effect can be observed – much stronger than if stimulation is applied during the relaxation phase of the heart, diastole.

Breathing is also important in this context: the stimulation was significantly more effective during the inhalation phase than during the exhalation phase.

“Our results show that synchronising vagus nerve stimulation with the heartbeat and breathing rhythm significantly increases effectiveness. This could help to improve the success of treatment for chronic illnesses, especially for those who have not previously responded to this therapy for reasons that are as yet unexplained,” says Eugenijus Kaniusas.

Larger clinical studies to follow

If nerve stimulation can be customised electronically so that it is tailored to the body’s own individual rhythms at any given time, it should be possible to achieve significantly greater successes than has been possible to date. Future studies should examine larger and clinically relevant patient groups and develop even more precise algorithms in order to be able to tailor the stimulation even more precisely to individual needs.

“This technology could be an effective and non-invasive way of modulating the autonomic nervous system in a targeted and gentle manner – a potential milestone in the neuromodulatory treatment of various chronic diseases,” believes Dr Joszef Constantin Szeles from the Vienna Private Clinic.

Source: Vienna University of Technology