Day: April 25, 2023

Categories : Mental Health NeurologyTags : Leave a comment

Improper ‘Pruning’ of Brain Connections may Cause Teen Mental Health Disorders

On By ModernMedia
Photo by Andrew Neel on Unsplash

Problems with the brain’s ability to ‘prune’ itself of unnecessary connections may underlie a wide range of mental health disorders that begin during adolescence, according to research published in Nature Medicine.

The findings, from an international collaboration, led by researchers in the UK, China and Germany, may help explain why people are often affected by more than one mental health disorder, and may in future help identify those at greatest risk.

One in seven adolescents (aged 10-19 years old) worldwide experiences mental health disorders, according to the World Health Organization (WHO). Depression, anxiety and behavioural disorders, such as attention deficit hyperactivity disorder (ADHD), are among the leading causes of illness and disability among young people, and adolescents will commonly have more than one mental health disorder.

Many mental health problems emerge during adolescence, such as depression and anxiety, which manifest as ‘internalising’ symptoms, including low mood and worrying. Other conditions such as attention deficit hyperactivity disorder (ADHD) manifest as ‘externalising’ symptoms, such as impulsive behaviour.

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: “Young people often experience multiple mental health disorders, beginning in adolescence and continuing – and often transforming – into adult life. This suggests that there’s a common brain mechanism that could explain the onset of these mental health disorders during this critical time of brain development.”

In the study, the researchers say they have identified a characteristic pattern of brain activity among these adolescents, which they have termed the ‘neuropsychopathological factor’, or NP factor for short.

The team examined data from 1,750 adolescents, aged 14 years, from the IMAGEN cohort, a European research project examining how biological, psychological, and environmental factors during adolescence may influence brain development and mental health. In particular, they examined imaging data from brain scans taken while participants took part in cognitive tasks, looking for patterns of brain connectivity – in other words, how different regions of the brain communicate with each other.

Adolescents who experienced mental health problems – regardless of whether their disorder was one of internalising or externalising symptoms, or whether they experienced multiple disorders – showed similar patterns of brain activity. These patterns – the NP factor – were largely apparent in the frontal lobes, the area at the front of the brain responsible for executive function which, among other functions, controls flexible thinking, self-control and emotional behaviour.

The researchers confirmed their findings by replicating them in 1799 participants from the ABCD Study in the USA, a long-term study of brain development and child health, and by studying patients who had received psychiatric diagnoses.

When the team looked at genetic data from the IMAGEN cohort, they found that the NP factor was strongest in individuals who carried a particular variant of the gene IGSF11 that has been previously associated with multiple mental health disorders. This gene is known to play an important role in synaptic pruning, a process whereby unnecessary brain connections – synapses – are discarded. Problems with pruning may particularly affect the frontal lobes, since these regions are the last brain areas to complete development in adolescents and young adults.

Dr Tianye Jia from the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China and the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK said: “As we grow up, our brains make more and more connections. This is a normal part of our development. But too many connections risk making the brain inefficient. Synaptic pruning helps ensure that brain activity doesn’t get drowned out in ‘white noise’.

“Our research suggests that when this important pruning process is disrupted, it affects how brain regions talk to each other. As this impact is seen most in the frontal lobes, this then has implications for mental health.”

The researchers say that the discovery of the NP factor could help identify those young people at greatest risk of compounding mental health problems.

Professor Jianfeng Feng from Fudan University in Shanghai, China, and the University of Warwick, UK, said: “We know that many mental health disorders begin in adolescence and that individuals who develop one disorder are at increased risk of developing other disorders, too. By examining brain activity and looking for this NP factor, we might be able to detect those at greatest risk sooner, offering us more opportunity to intervene and reduce this risk.”

Source: University of Cambridge

Categories : Obstetrics & GynaecologyTags : Leave a comment

Chinese Traditional Medicine in Pregnancy Linked to Increased Congenital Malformations

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A new study published in the journal Acta Obstetricia et Gynecologica Scandinavica has uncovered an association between the use of traditional Chinese medicine during pregnancy and congenital malformations, including heart defects, in children.

In the prospective study, 16 751 women who received obstetrics care from hospitals in China completed a survey on their use of traditional Chinese medicine before and during pregnancy. Among foetuses, there were 273 congenital malformations.

Foetuses exposed to traditional Chinese medicine had 2.1-times higher odds of developing congenital malformations compared with those without exposure. There were significant associations with congenital malformations in women with early pregnant use of traditional Chinese medicine and for those who used two or more types of these products.

“To improve traditional Chinese medicine, we should pay more attention to its hazards – especially the identification of teratogenic ingredients – while also evaluating its therapeutic effects,” said corresponding author Jiang-Nan Wu, of Obstetrics and Gynecology Hospital of Fudan University, in China.

Source: Wiley

Categories : Mental Health Substance UseTags : Leave a comment

Suicide Attempts Show Increasing Exposures to Cannabis

On By ModernMedia
Photo by Kindel Media on Unsplash

Analysis of US poison centre data has shown that suspected suicidal cannabis exposures have increased 17% annually, over a period of 12 years. According to the study published in the journal JAMA Network Open, more than 92%, involved other substances in addition to cannabis, and the data cannot show a direct causal link between cannabis and suicide attempts.

Still, the findings are cause for concern, the researchers said, especially since the increase was more pronounced among children and women during and after the pandemic.

“This study adds to already ample evidence that cannabis use, particularly by younger people, has significant implications for mental health,” said study co-author Tracy Klein, a WSU associate professor of nursing. “We don’t have evidence that cannabis alone was the primary driver of a suicide attempt, but we do know that cannabis can worsen certain mental health conditions and increase impulsivity.”

The researchers found 18,698 cases of intentional, suspected suicide cannabis exposures reported to U.S. poison centers from 2009 to 2021. Of these cases, 9.6% resulted in death or major outcomes such as permeant disability. The researchers noted that while more of these exposures involved younger people, severe consequences occurred more often among people 65 and older.  

U.S. poison centers take calls 24-hours a day from households and healthcare facilities to provide toxicology expertise in suspected poisoning cases. They also investigate the causes, often following up with patients and doctors to determine if patients took substances intentionally or not.

It is well known that accidental cannabis poisonings have been increasing since many states legalized cannabis. Some policies can help prevent these unintentional cases, Klein said, such as packaging guidelines so edible cannabis products are not mistaken for candy.

Intentional cannabis poisonings, on the other hand, have not been well studied, which is one of the reasons the researchers undertook this analysis, and their findings point to the need for more mental health services.

“We have a significant shortage of mental health and primary care providers in the United States,” Klein said. “We know that mental health needs not only changed but became even more acute during the COVID-19 emergency. Cannabis is one part of that.”

Other research has shown that cannabis use is associated with depression and anxiety in youth and that it may interfere with brain development as well. Recent studies have also suggested a link between suicidal ideation and cannabis use in young people. Given this evidence, it is especially important to limit youth access to cannabis, said Janessa Graves, first author and a WSU nursing associate professor.  

“Children and adolescents shouldn’t be able to purchase or access cannabis,” Graves said. “We also need to educate kids and parents around the risks of cannabis. I think many people just aren’t aware the impacts cannabis can have on brain development, and on behavioural and mental health, especially in adolescents and young adults.”

Source: Washington State University

Categories : Antibiotics Diseases, Syndromes and ConditionsTags : Leave a comment

Experimental Biologic Drug Defeats MRSA in Early Lab Tests

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Methicillin-resistant Staphylococcus aureus (MRSA). Image by CDC on Unsplash

Researchers reported in Cell Host & Microbe that early tests of a bioengineered drug candidate were successful in countering Staphylococcus aureus, a bacteria particularly dangerous to hospitalised patients. 

Experiments demonstrated that SM1B74, an antibacterial biologic agent, was superior to a standard antibiotic drug at treating mice infected with S. aureus, including its treatment-resistant form known as MRSA.

The researchers tested mAbtyrins, a combination molecule based on an engineered version of a human monoclonal antibody (mAb), a protein that clings to and marks S. aureus for uptake and destruction by immune cells. Attached to the mAb are centyrins, small proteins that prevent these bacteria from boring holes into the human immune cells in which they hide. As the invaders multiply, these cells die and burst, eliminating their threat to the bacteria.

Together, the experimental treatment targets ten disease-causing mechanisms employed by S. aureus, but without killing it, say the study authors. This approach promises to address antibiotic resistance, say the researchers, where antibiotics kill vulnerable strains first, only to make more space for others that happen to be less vulnerable until the drugs no longer work.

“To our knowledge, this is the first report showing that mAbtyrins can drastically reduce the populations of this pathogen in cell studies, and in live mice infected with drug-resistant strains so common in hospitals,” said lead study author Victor Torres, PhD, the C.V. Starr Professor of Microbiology and director of the NYU Langone Health Antimicrobial-Resistant Pathogen Program.”Our goal was to design a biologic that works against S. aureus inside and outside of cells, while also taking away the weapons it uses to evade the immune system.”

Inside Out

The new study is the culmination of a five-year research partnership between scientists at NYU Grossman School of Medicine and Janssen to address the unique nature of S. aureus.

The NYU Langone team together with Janssen researchers, published in 2019 a study that found that centyrins interfere with the action of potent toxins used by S. aureus to bore into immune cells. They used a molecular biology technique to make changes in a single parental centyrin, instantly creating a trillion slightly different versions of it via automation. Out of this “library,” careful screening revealed a small set of centyrins that cling more tightly to the toxins blocking their function.

Building on this work, the team fused the centyrins to a mAb originally taken from a patient recovering from S. aureus infection. Already primed by its encounter with the bacteria, the mAb could label the bacterial cells such that they are pulled into bacteria-destroying pockets inside of roving immune cells called phagocytes. That is unless the same toxins that enable S. aureus to drill into immune cells from the outside let it drill out of the pockets to invade from the inside.

In a “marvel of bioengineering,” part of the team’s mAbtyrin serves as the passport recognised by immune cells, which then engulf the entire, attached mAbtyrin, along with its centyrins, and fold it into the pockets along with bacteria. Once inside, the centyrins block the bacterial toxins there. This, say the authors, sets their effort apart from antibody combinations that target the toxins only outside of cells.

The team made several additional changes to their mAbtyrin that defeat S. aureus by, for instance, activating chain reactions that amplify the immune response, as well by preventing certain bacterial enzymes from cutting up antibodies and others from gumming up their action.

The researchers tracked the growth of S. aureus strains commonly occurring in US communities in the presence of primary human immune cells (phagocytes). Bacterial populations grew almost normally in the presence of the parental antibody, slightly less well in the presence of the team’s engineered mAb, and half as fast when the mAbtyrin was used.

In another test, 98% of mice treated with a control mAb (no centyrins) developed bacteria-filled sores on their kidneys when infected with a deadly strain of S. aureus, while only 38% of mice did so when treated with the mAbtyrin. Further, when these tissues were removed and colonies of bacteria in them counted, the mice treated with the mAbtyrin had one hundred times (two logs) fewer bacterial cells than those treated with a control mAb.

Finally, the combination of small doses of the antibiotic vancomycin with the mAbtyrin in mice significantly improved the efficacy of the mAbtyrin, resulting in maximum reduction of bacterial loads in the kidneys and greater than 70% protection from kidney lesions.

“It is incredibly important,” said Torres, “that we find new ways to boost the action of vancomycin, a last line of defence against MRSA.”

Source: NYU Langone Health / NYU Grossman School of Medicine

Categories : Cardiovascular Disease Pain ManagementTags : Leave a comment

Researchers Quantify Risk Factors for Oral Diclofenac

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Safety concerns related to the widely used analgesic diclofenac may be tied to a little-studied drug-metabolising enzyme which can vary as much as 3000 times across individuals, according to new research published in the journal Clinical Pharmacology & Therapeutics.

The findings could be used to develop ways to identify those at risk of serious side effects from the drug. They may help determine safer dosing standards for specific populations, including women, young children and people of certain ethnicities.

Used to treat arthritis-associated pain and inflammation, diclofenac was available over-the-counter in the US until 2013, when the Food and Drug Administration restricted it to prescription-only use following reports of the drug causing heart damage. More than 10 million prescriptions per year are written for it in the US. It is also one of the most widely used non-steroidal anti-inflammatory drugs worldwide, and is still over-the-counter in many countries. 

“Most patients who are using diclofenac have arthritis, and many of them are at risk of heart disease,” senior author Bhagwat Prasad, an associate professor at Washington State University. “So there is a concern that taking diclofenac may be putting them at even greater risk of cardiovascular events such as heart attack and stroke.”

Previous findings by the WSU team had found a high degree of variability in the expression of UGT2B17, an enzyme that is a known player in diclofenac metabolism. They found that the enzyme is present at much lower levels in women than in men, which could explain the increased risk of heart damage seen in women taking diclofenac. The enzyme was also mostly absent in children under age 9 and discovered large ethnicity-based differences in the number of people who lack the gene for the enzyme altogether, which ranges from around 20% of Caucasians up to around 90% of Japanese people.

In this new study, the WSU researchers used human liver and intestinal samples along with computer modelling to quantify the degree to which this enzyme contributes to diclofenac metabolism relative to other related enzymes. They found it to be a major player, supporting the idea that low levels of the UGT2B17 enzyme may be the cause of heart damage tied to diclofenac use.

“No one knew why this heart toxicity is happening in some individuals,” said first author Deepak Ahire, a graduate student in the WSU College of Pharmacy and Pharmaceutical Sciences. “Our study showed, for the first time, that UGT2B17 is important in diclofenac metabolism and suggests that differences in UGT2B17 expression are what makes people’s response to diclofenac so variable, leading to toxicity in some whereas for others the drug simply does not work.”

Ahire said that their study found that this enzyme metabolises diclofenac mainly in the intestine, unlike other related enzymes that are active mostly in the liver. Thus the observed effects are limited to diclofenac tablets taken by mouth, which provides for the quickest absorption and pain relief.

The findings suggest genetic testing could help healthcare providers evaluate safety risks before prescribing diclofenac. Prasad also noted that drug regulatory authorities in countries where diclofenac is still available over the counter should consider doing efficacy testing to determine the optimal dose of the drug for their local market.

The WSU researchers are currently in the process of confirming their findings in a pilot clinical trial. Their next step would be to pursue collaborations with large hospitals to study the connection between diclofenac and heart damage in patients’ electronic medical records.

Source: Washington State University