Stanford scientist, after decades of study, concludes: We don’t have free will

Story by Corinne Purtill

Before epilepsy was understood to be a neurological condition, people believed it was caused by the moon, or by phlegm in the brain. They condemned seizures as evidence of witchcraft or demonic possession, and killed or castrated sufferers to prevent them from passing tainted blood to a new generation.

Today we know epilepsy is a disease. By and large, it’s accepted that a person who causes a fatal traffic accident while in the grip of a seizure should not be charged with murder.

That’s good, says Stanford University neurobiologist Robert Sapolsky. That’s progress. But there’s still a long way to go.

After more than 40 years studying humans and other primates, Sapolsky has reached the conclusion that virtually all human behavior is as far beyond our conscious control as the convulsions of a seizure, the division of cells or the beating of our hearts.

This means accepting that a man who shoots into a crowd has no more control over his fate than the victims who happen to be in the wrong place at the wrong time. It means treating drunk drivers who barrel into pedestrians just like drivers who suffer a sudden heart attack and veer out of their lane.

“The world is really screwed up and made much, much more unfair by the fact that we reward people and punish people for things they have no control over,” Sapolsky said. “We’ve got no free will. Stop attributing stuff to us that isn’t there.”

Sapolsky, a MacArthur “genius” grant winner, is extremely aware that this is an out-there position. Most neuroscientists believe humans have at least some degree of free will. So do most philosophers and the vast majority of the general population. Free will is essential to how we see ourselves, fueling the satisfaction of achievement or the shame of failing to do the right thing.

Saying that people have no free will is a great way to start an argument. This is partly why Sapolsky, who describes himself as “majorly averse to interpersonal conflict,” put off writing his new book “Determined: A Science of Life Without Free Will.”

Sapolsky, 66, has a mild demeanor and a Jerry Garcia beard. For more than three decades, he escaped the politics of academia to study baboons in rural Kenya for a few months every year.

“I’m really, really, really trying not to sound like a combative jerk in the book,” he said. “I deal with human complexities by going and living in a tent. So yeah, I’m not up for a lot of brawls about this.”

Analyzing human behavior through the lens of any single discipline leaves room for the possibility that people choose their actions, he says. But after a long cross-disciplinary career, he feels it’s intellectually dishonest to write anything other than what he sees as the unavoidable conclusion: Free will is a myth, and the sooner we accept that, the more just our society will be.

“Determined,” which comes out today, builds on Sapolsky’s 2017 bestseller “Behave: The Biology of Humans at Our Best and Worst,” which won the Los Angeles Times Book Prize and a slew of other accolades.

The book breaks down the neurochemical influences that contribute to human behaviors, analyzing the milliseconds to centuries preceding, say, the pulling of a trigger or the suggestive touch on an arm.

“Determined” goes a step further. If it’s impossible for any single neuron or any single brain to act without influence from factors beyond its control, Sapolsky argues, there can be no logical room for free will.

Many people with even a passing familiarity with human biology can comfortably agree with this — up to a point.

We know we make worse decisions when hungrystressed or scared. We know our physical makeup is influenced by the genes inherited from distant ancestors and by our mothers’ health during her pregnancy. Abundant evidence indicates that people who grew up in homes marked by chaos and deprivation will perceive the world differently and make different choices than people raised in safe, stable, resource-rich environments. A lot of important things are beyond our control.

But, like — everything? We have no meaningful command over our choice of careers, romantic partners or weekend plans? If you reach out right now and pick up a pen, was even that insignificant action somehow preordained?

Yes, Sapolsky says, both in the book and to the countless students who have asked the same question during his office hours. What the student experiences as a decision to grab the pen is preceded by a jumble of competing impulses beyond his or her conscious control. Maybe their pique is heightened because they skipped lunch; maybe they’re subconsciously triggered by the professor’s resemblance to an irritating relative.

Then look at the forces that brought them to the professor’s office, feeling empowered to challenge a point. They’re more likely to have had parents who themselves were college educated, more likely to hail from an individualistic culture rather than a collective one. All of those influences subtly nudge behavior in predictable ways.

You may have had the uncanny experience of talking about an upcoming camping trip with a friend, only to find yourself served with ads for tents on social media later. Your phone didn’t record your conversation, even if that’s what it feels like. It’s just that the collective record of your likes, clicks, searches and shares paints such a detailed picture of your preferences and decision-making patterns that algorithms can predict — often with unsettling accuracy — what you are going to do.

Something similar happens when you reach for that pen, Sapolsky says. So many factors beyond your conscious awareness brought you to that pen that it’s hard to say how much you “chose” to pick it up at all.

Sapolsky was raised in an Orthodox Jewish household in Brooklyn, the son of immigrants from the former Soviet Union.

Biology called to him early — by grade school he was writing fan letters to primatologists and lingering in front of the taxidermied gorillas at the American Museum of Natural History — but religion shaped life at home.

That all changed on a single night in his early teens, he says. While grappling with questions of faith and identity, he was struck by an epiphany that kept him awake until dawn and reshaped his future: God is not real, there is no free will, and we primates are pretty much on our own.

“That was kind of a big day,” he said with a chuckle, “and it’s been tumultuous since then.”

Skeptics could seize on this to rebut his arguments: If we aren’t free to choose our actions or beliefs, how does a boy from a deeply religious conservative home become a self-professed liberal atheist?

Change is always possible, he argues, but it comes from external stimuli. Sea slugs can learn to reflexively retreat from an electrical shock. Through the same biochemical pathways, humans are changed by exposure to external events in ways we rarely see coming.

Imagine, he offers, a group of friends that goes to see a biopic about an inspiring activist. One applies the next day to join the Peace Corps. One is struck by the beautiful cinematography and signs up for a filmmaking course. The rest are annoyed they didn’t see a Marvel film.

All of the friends were primed to respond as they did when they sat down to watch. Maybe one had heightened adrenaline from a close call with another car on the drive over; maybe another was in a new relationship and awash in oxytocin, the so-called love hormone. They had different levels of dopamine and serotonin in their brains, different cultural backgrounds, different sensitivities to sensory distractions in the theater. None chose how the stimulus of the film would affect them anymore than the sea slug “decided” to wince in response to a jolt.

For fellow adherents of determinism — the belief that it’s impossible for a person in any situation to have acted differently than they did — Sapolsky’s scientific defense of the cause is welcome.

“Who we are and what we do is ultimately the result of factors beyond our control and because of this we are never morally responsible for our actions in the sense that would make us truly deserving of praise and blame, punishment and reward,” said Gregg Caruso, a philosopher at SUNY Corning who read early drafts of the book. “I am in agreement with Sapolsky that life without belief in free will is not only possible but preferable.”

Caruso is co-director of the Justice Without Retribution Network, which advocates for an approach to criminal activity that prioritizes preventing future harm rather than assigning blame. Focusing on the causes of violent or antisocial behavior instead of fulfilling a desire for punishment, he said, “will allow us to adopt more humane and effective practices and policies.”

Theirs is very much a minority viewpoint.

Sapolsky is “a wonderful explainer of complex phenomena,” said Peter U. Tse, a Dartmouth neuroscientist and author of the 2013 book “The Neural Basis of Free Will.” “However, a person can be both brilliant and utterly wrong.”

Neural activity is highly variable, Tse said, with identical inputs often resulting in non-identical responses in individuals and populations. It’s more accurate to think of those inputs as imposing parameters rather than determining specific outcomes. Even if the range of potential outcomes is limited, there’s simply too much variability at play to think of our behavior as predetermined.

What’s more, he said, it’s harmful to do so.

“Those who push the idea that we are nothing but deterministic biochemical puppets are responsible for enhancing psychological suffering and hopelessness in this world,” Tse said.

Even those who believe biology limits our choices are wary of how openly we should embrace that.

Saul Smilansky, a philosopher at the University of Haifa in Israel and author of the book “Free Will and Illusion,” rejects the idea that we can will ourselves to transcend all genetic and environmental constraints. But if we want to live in a just society, we have to believe that we can.

“Losing all belief in free will and moral responsibility would likely be catastrophic,” he said, and encouraging people to do so is “dangerous, even irresponsible.”

widely cited 2008 study found that people who read passages dismissing the idea of free will were more likely to cheat on a subsequent test. Other studies have found that people who feel less control over their actions care less about making mistakes in their work, and that disbelief in free will leads to more aggression and less helpfulness.

Sapolsky discusses such concerns in his book, ultimately concluding that the effects seen in such experiments are too small and their lack of reproducibility too great to support the idea that civilization will crumble if we think we can’t control our fates.

The more compelling critique, he says, is eloquently articulated in the short story “What’s Expected of Us,” by speculative fiction writer Ted Chiang. The narrator describes a new technology that convinces users their choices are predetermined, a discovery that saps them of their will to live.

“It’s essential that you behave as if your decisions matter,” the narrator warns, “even though you know that they don’t.”

The greatest risk of abandoning free will, Sapolsky concedes, isn’t that we’ll want to do bad things. It’s that, without a sense of personal agency, we won’t want to do anything.

“It may be dangerous to tell people that they don’t have free will,” Sapolsky said. “The vast majority of the time, I really think it’s a hell of a lot more humane.”

Sapolsky knows he won’t persuade most of his readers. It’s hard to convince people who have been harmed that perpetrators deserve less blame because of their history of poverty. It’s even harder to convince the well-off that their accomplishments deserve less praise because of their history of privilege.

“If you have time to be bummed out by that, you’re one of the lucky ones,” he said.

His true hope, he says, is to increase compassion. Maybe if people understand how thoroughly an early history of trauma can rewire a brain, they’ll stop lusting for harsh punishments. Maybe if someone realizes they have a brain condition like depression or ADHD, they’ll stop hating themselves for struggling with tasks that seem easier for others.

Just as previous generations thought seizures were brought on by witchcraft, some of our current beliefs about personal responsibility may eventually be undone by scientific discovery.

We are machines, Sapolsky argues, exceptional in our ability to perceive our own experiences and feel emotions about them. It is pointless to hate a machine for its failures.

There is only one last thread he can’t resolve.

“It is logically indefensible, ludicrous, meaningless to believe that something ‘good’ can happen to a machine,” he writes. “Nonetheless, I am certain that it is good if people feel less pain and more happiness.”

Stanford scientist, after decades of study, concludes: We don’t have free will (msn.com)

Google Street View predicts heart disease risk based on neighborhood features

Researchers have used Google Street View to study hundreds of elements of the built environment, including buildings, green spaces, pavements and roads, and how these elements relate to each other and influence coronary artery disease in people living in these neighborhoods.

Their findings, published in the European Heart Journal today (Thursday), show that these factors can predict 63% of the variation in the risk of coronary heart disease from one area to another.

Coronary heart disease, where a build-up of fatty substances in the coronary arteries interrupts the blood supply to the heart, is one of the most common forms of cardiovascular disease.

Researchers say that using Google Street View can help provide an overview of physical environmental risk factors in the built and natural environments that could help not only in understanding risk factors in these environments, but ultimately help towards building or adapting towns and cities to make them healthier places to live.

The study was led by Prof. Sadeer Al-Kindi and Prof. Sanjay Rajagopalan from University Hospitals Harrington Heart & Vascular Institute and Case Western Reserve University, Ohio, USA, and Dr. Zhuo Chen, a post-doctoral fellow in Prof. Rajagopalan’s laboratory.

Prof. Rajagopalan said: “We have always been interested in how the environment, both the built and natural environment, influences cardiovascular disease. Here in America, they say that the zip code is a better predictor of heart disease than even personal measures of health. However, to investigate how the environment influences large populations in multiple cities is no mean task. Hence, we used machine vision-based approaches to assess the links between the built environment and coronary heart disease prevalence in US cities.”

The study included more than half a million Google Street View images of Detroit, Michigan; Kansas City, Missouri; Cleveland, Ohio; Brownsville, Texas; Fremont, California; Bellevue, Washington State; and Denver, Colorado. Researchers also collected data on rates of coronary heart disease according to ‘census tracts’. These are areas smaller than a US zip code that are home to an average of 4,000 people. The researchers used an approach called a convolutional neural network; a type of artificial intelligence that can recognize and analyze patterns in images to make predictions.

The research revealed that features of the built environment visible on Google Street View images could predict 63% of the variation in coronary heart disease between these small regions of US cities.

Prof. Al-Kindi added: “We also used an approach called attention mapping, which highlights some of the important regions in the image, to provide a semi-qualitative interpretation of some of the thousands of features that may be important in coronary heart disease. For instance, features like green space and walkable roads were associated with lower risk, while other features, such as poorly paved roads, were associated with higher risk. However, these findings need further investigation.

“We’ve shown that we can use computer vision approaches to help identify environmental factors influencing cardiovascular risk and this could play a role in guiding heart-healthy urban planning. The fact that we can do this at scale is something that is absolutely unique and important for urban planning.”

“With upcoming challenges including climate change and a shifting demographic, where close to 70% of the world’s population will live in urban environments, there is a compelling need to understand urban environments at scale, using computer vision approaches that can provide exquisite detail at an unparalleled level,” said Prof. Rajagopalan.

In an accompanying editorial, Dr. Rohan Khera from Yale University School of Medicine, USA said: “The association of residential location with outcomes often supersedes that of known biological risk factors. This is often summarised with the expression that a person’s postal code is a bigger determinant of their health than their genetic code. However, our ability to appropriately classify environmental risk factors has relied on population surveys that track wealth, pollution, and community resources.

“The study by Chen and colleagues presents a novel and more comprehensive evaluation of the built environment. This work creatively leverages Google’s panoramic street-view imagery that supplements its widely used map application.

“… an AI-enhanced approach to studying the physical environment and its association with cardiovascular health highlights that across our communities, measures of cardiovascular health are strongly encoded in merely the visual appearance of our neighborhoods. It is critical to use this information wisely, both in defining strategic priorities for identifying vulnerable communities and in redoubling efforts to improve cardiovascular health in communities that need it most.”

https://www.msn.com/en-gb/health/other/google-street-view-predicts-heart-disease-risk-based-on-neighborhood-features/ar-BB1kFeqv

Single-dose drug to quash anxiety in trials

By Bronwyn Thompson

An effective single-dose, long-term treatment for anxiety could be within reach, with the phase 2b clinical trial of MM-120 reported to have passed the stage with flying colors. The makers, MindMed, now plan to hold an end-of-phase meeting with the US Food and Drug Administration (FDA) in early 2024, and then get a phase 3 trial under way.

MM-120 is essentially lysergide D-tartrate, which is best known by its abbreviation, LSD. A synthetic tryptamine, this serotonergic hallucinogen acts as a partial agonist at serotonin (5-hydroxytryptamine [5-HT]) 5-HT2A receptors. MindMed has developed a tartrate form of lysergide to treat generalized anxiety disorder (GAD) and, in a separate trial, attention-deficit hyperactivity disorder (ADHD).

The company has reported that the phase 2b clinical trial of 200 participants with GAD symptoms had met its primary endpoint with “positive topline results,” paving the way for taking it to the next trial stage and closer to therapeutic approval.

“Clinically meaningful improvements,” compared to a placebo, were noted in groups on 100 µg and 200 µg doses. MM-120 was reportedly well tolerated, with side effects such as hallucinations and euphoric mood only occurring on dose day.

Not surprisingly, given its one-off dose and it being a standalone drug – so with no psychotherapy aspect to the trial – 90% of the 200 participants completed the four-week trial and 97.5% in the high-dose groups saw it through to the end.

“We are excited by the strong positive results for MM-120 in GAD, particularly given that this is the first study to assess the standalone drug effects of MM-120 in the absence of any psychotherapeutic intervention,” said MindMed director Robert Barrow in a statement. “These promising findings represent a major step forward in our goal to bring a paradigm-shifting treatment to the millions of patients who are profoundly impacted by GAD.”

GAD, which can be a hugely debilitating subtype of anxiety disorder, is hallmarked by chronic excessive worry that can impact work, health and relationships. Of the estimated 6.8 million Americans who have GAD, less than half are receiving any treatment for it.

It’s also notoriously difficult to treat, with around half of those who do seek medical intervention not responding to initial treatment.

In the study, 100 µg of MM-120 administered once, showed remarkable results four weeks later. Using the Hamilton Anxiety Rating Scale (HAM-A), remission rates and Clinical Global Impressions – Severity (CGI-S) scores, the drug’s performance shows great promise.

Looking at clinical response, with a 50% or greater improvement in HAM-A scores after the fourth week, 78% of the participants had significant GAD relief compared to the placebo, while clinical remission – a HAM-A score below seven – was shown in a massive 50% of participants who had received the 100-µg dose.

Overall, participants receiving 100 µg or 200 µg experienced a two-unit improvement in the CGI-S score at the four-week assessment.

“Generalized anxiety disorder is a common condition associated with significant impairment that adversely affects millions of people and there remains a serious unmet need for this patient population,” said Daniel Karlin, Chief Medical Officer of MindMed. “The pharmaceutical industry has largely ignored GAD over recent decades as it has proved extremely difficult to target. Few new treatment options have shown robust activity in GAD since the last new drug approval in 2004, making the strong, rapid, and durable clinical activity of a single dose of MM-120 observed in the trial particularly notable.

“We believe this study is the first to rigorously assess the efficacy of a drug candidate in this class in the absence of a concurrent therapeutic intervention, which brings hope to the millions of people suffering from GAD and provides additional evidence that MM-120 may play an important role in revolutionizing the treatment of brain health disorders,” he added in the statement.

https://newatlas.com/medical/single-dose-drug-quash-anxiety-trial

New test for oral cancer

Aaron Weinberg of Case Western Reserve University

Oral cancers and precancerous mouth lesions are considered especially difficult to diagnose early and accurately.

For one, biopsies are expensive, invasive, stressful for the patient and can lead to complications. They’re also not feasible if repeated screenings of the same lesion are required.

But a team of researchers, led by a clinician scientist at Case Western Reserve University School of Dental Medicine, has discovered a noninvasive, low-cost test to detect oral cancer, monitor precancerous lesions and determine when a biopsy is warranted.

Their findings, published online March 4 in the journal Cell Reports Medicine are based on a scoring system linked to the levels of two proteins in cells brushed from suspicious oral lesions of patients at dental clinics or the ear, nose and throat department at University Hospitals (UH).

One of the proteins (human beta defensin 3 or hBD-3) is expressed at high levels in early-stage oral cancer, while the second (hBD-2) is low or unchanged.

The ratio of hBD-3 to hBD-2 in the lesion site—over the ratio of the two proteins on the opposite, normal site—generates a score, called the beta defensin index (BDI).

A score above a predetermined threshold implies cancer; anything below does not. Determining the levels of the proteins and quantifying the BDI is done routinely in a lab.

The BDI was independently validated using identical protocols at CWRU/UH, University of Cincinnati Medical Center and West Virginia University School of Dentistry.

“When we first discovered hBD-3, we saw it acted as a ‘good guy,’ involved in wound-healing and killing microbes,” said Aaron Weinberg, chair of the Department of Biological Sciences at the Case Western Reserve School of Dental Medicine and the study’s lead researcher. “When we found it was regulated the same way certain cells grow uncontrollably, we started studying hBD-3 in the context of oral cancer.

“Imagine our surprise when this Dr. Jekyll turned out to be Mr. Hyde,” he said. “We found it was not only promoting tumor growth but was overexpressed in the early stages of the disease, while another member, hBD-2, wasn’t changing. This difference in levels of expression of the two proteins compared to the opposite side in the same patient led us to examine the BDI’s ability to distinguish cancer from benign lesions.”

Weinberg credits School of Dental Medicine instructor Santosh Ghosh for navigating the BDI scoring process.

Head and neck cancer (HNC), of which oral cancer is about 90%, is the seventh-most prevalent malignancy in the world, and developing countries are witnessing a rise in its incidence. HNC makes up about 5% of all cancers worldwide and 3% of all malignancies in the United States, according to the National Institutes of Health. There are about 640,000 cases of HNC per year, resulting in about 350,000 deaths worldwide, mainly in socioeconomically disadvantaged populations and underserved communities.

The study’s lab-based approach, which is now patented, can reduce biopsies in primary care clinics by 95% because it can tell clinicians who actually needs a biopsy, said Weinberg, also secondarily appointed in the Departments of Pathology and Otolaryngology at Case Western Reserve School of Medicine. The test can also be used in developing countries where oral cancer is rampant and pathology services are questionable or lacking, he said.

The positive data from the lab-based approach has inspired the development of a point-of-care (POC) device in collaboration with Umut Gurkan, the Wilbert J. Austin Professor of Engineering at the Case School of Engineering. The POC diagnostic approach measures the protein ratio and could be used directly in a clinic, providing results within half-hour.

Working through Case Western Reserve’s Technology Transfer Office, a patent for the device is pending, setting up possible manufacturing and clinical validation as a next step.

Discovery, clinical validation studies and POC technology development were supported by the National Institute of Dental and Craniofacial Research, National Cancer Institute, Case Coulter Translational Research Partnership and Ohio Third Frontier Technology Validation and Start-Up Fund.

Intervention Reduces Likelihood of Developing Postpartum Anxiety, Depression by More Than 70%

Results from a large clinical trial, published in Nature Medicine, showed that an intervention for anxiety provided to pregnant women significantly reduced the likelihood of the women developing moderate-to-severe anxiety, depression, or both 6 weeks after birth.

The unique intervention was administered by non-specialised providers who had the equivalent

of a bachelor’s degree in psychology, but no clinical experience. The results suggest this intervention could be an effective way to prevent the development of postpartum mental health challenges in women living in low-resource settings.

“In low resource settings, it can be challenging for women to access mental health care due to a global shortage of trained mental health specialists,” said Joshua A. Gordon, MD, National Institute of Mental Health, part of the National Institutes of Health, Bethesda, Maryland. “This study shows that non-specialists could help to fill this gap, providing care to more women during this critical period.”

Led by Pamela J. Surkan, PhD, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, the study was conducted in the Punjab Province of Pakistan between April 2019 and January 2022. Pregnant women with symptoms of at least mild anxiety were randomised to receive either routine pregnancy care or a cognitive behavioural therapy (CBT)-based intervention called Happy Mother-Healthy Baby. The researchers assessed the participants (380 women in the CBT group and 375 women in the routine care group) for anxiety and depression 6 weeks after the birth of their child.

The researchers found that 9% of women in the intervention group developed moderate-to-severe anxiety compared with 27% of women in the routine care group, and 12% percent of women in the intervention group developed depression compared with 41% of women in the routine care group.

“Postpartum depression not only harms mothers, it is also associated with poorer physical growth and delayed cognitive development in their children,” said Dr. Surkan. “The link between maternal and child health highlights the critical importance of developing effective ways to address postpartum anxiety and depression.”

Women who received the Happy Mother-Healthy Baby intervention took part in 6 intervention sessions where they learned to identify anxious thoughts and behaviours, such as thoughts about possible miscarriage, and to practise replacing them with helpful thoughts and behaviours. The first 5 sessions were conducted in early to mid-pregnancy, and the sixth session occurred in the third trimester.

“In the future, we can build on these findings through implementation research,” said Dr. Surkan. “Having identified an intervention that works, the next step is to figure out the best ways to deliver effective treatment to the people who need it, bridging the gap between science and practice.”

Reference: https://www.nature.com/articles/s41591-024-02809-x

https://dgnews.docguide.com/article/intervention-reduces-likelihood-of-developing-postpartum-anxiety-depression-by-more-than-70

Researchers identify new therapeutic approach targeting astrocytes, the brain’s most abundant cells

A team led by scientists at Case Western Reserve University School of Medicine has identified a new therapeutic approach for combating neurodegenerative diseases, offering hope of improved treatments for Alzheimer’s disease, Parkinson’s disease, Vanishing White Matter disease and multiple sclerosis, among others. 

Neurodegenerative diseases, which affect millions of people worldwide, occur when nerve cells in the brain or nervous system lose function over time and ultimately die, according to the National Institutes of Health. Alzheimer’s disease and Parkinson’s disease are the most common.

The research team’s new study, published online Feb. 20 in the journal Nature Neuroscience, focused on astrocytes—the brain’s most abundant cells, which normally support healthy brain function. Growing evidence indicates astrocytes can switch to a harmful state that increases nerve-cell loss in neurodegenerative diseases.

The researchers created a new cellular technique to test thousands of possible medications for their ability to prevent these rogue astrocytes from forming. 

“By harnessing the power of high-throughput drug-screening, we’ve identified a key protein regulator that, when inhibited, can prevent the formation of harmful astrocytes,” said Benjamin Clayton, lead author and National Multiple Sclerosis Society career transition fellow in the laboratory of Paul Tesar at the Case Western Reserve School of Medicine.

They found that blocking the activity of a particular protein, HDAC3, may prevent the development of dangerous astrocytes. The scientists discovered that by administering medications that specifically target HDAC3, they were able to prevent the development of dangerous astrocytes and significantly increase the survival of nerve cells in mouse models.

“This research establishes a platform for discovering therapies to control diseased astrocytes and highlights the therapeutic potential of regulating astrocyte states to treat neurodegenerative diseases,” said Tesar, the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and the study’s principal investigator.  

Tesar, also director of the School of Medicine’s Institute for Glial Sciences, said more research needs to be done before patients might benefit from the promising approach. But, he said, their findings could lead to the creation of novel therapies that disarm harmful astrocytes and support neuroprotection—perhaps improving the lives of people with neurodegenerative illnesses in the future.

“Therapies for neurodegenerative disease typically target the nerve cells directly,” Tesar said, “but here we asked if fixing the damaging effects of astrocytes could provide therapeutic benefit. Our findings redefine the landscape of neurodegenerative disease treatment and open the door to a new era of astrocyte targeting medicines.”

Additional contributing researchers from the Case Western Reserve School of Medicine, and from the George Washington School of MedicineThe Ohio State University and the University of Tampa included James Kristell, Kevin Allan, Erin Cohn, Yuka Maeno-Hikichi, Annalise Sturno, Alexis Kerr, Elizabeth Shick, Molly Karl, Eric Garrison, Robert Miller, Andrew Jerome, Jesse Sepeda, Andrew Sas, Benjamin Segal, and Eric Freundt.

The research was supported by grants from the National Institutes of Health, National Multiple Sclerosis Society and Hartwell Foundation, and philanthropic support by sTF5 Care and the R. Blane & Claudia Walter, Long, Goodman, Geller and Weidenthal families.

Closing toilet lid doesn’t stop spread of germs during flush

By Dennis Thompson, HealthDay News

It’s been said that closing the toilet lid before flushing can prevent the spread of all germs, by keeping any flush-produced mist in the bowl.

But a new study refutes that, showing that tiny viral particles spread to many restroom surfaces during toilet flushing — whether the lid is up or down.

The only effective way of reducing the spread of virus was through disinfection of the toilet, toilet water and nearby surfaces, researchers report Thursday in the American Journal of Infection Control.

“With results showing that closing toilet lids has no meaningful impact on preventing the spread of viral particles, our study highlights the importance of regular disinfection of toilets to reduce contamination and prevent the spread of viruses,” said senior researcher Charles Gerba, a professor of virology at the University of Arizona.

Prior research has demonstrated that flushing a toilet creates an aerosol plume that can travel five feet or more, spreading germs to floors, walls, sinks and other surfaces in a bathroom, researchers said in background notes.

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Studies have also found that closing the toilet lid can reduce the spread of harmful bacteria in a bathroom.

However, until now no one had studied whether the same held true for viruses, which tend to be much smaller than bacteria, researchers noted.

In this study, they analyzed the spread of viral particles induced by flushing with an open or closed toilet lid.

The team seeded toilets with varying doses of a virus that’s not harmful to humans, and then collected samples from toilet bowl water and various bathroom surfaces.

Leaving the lid up or down made no difference in the amount of virus collected from bathroom surfaces, the researchers found. The toilet seat was the most contaminated surface.

Researchers also analyzed the effects of cleaning the toilet, both with and without disinfectant.

Cleaning with just a toilet brush left behind substantial viral contamination, but cleaning with a disinfectant and a brush significantly reduced the amount of virus found in the toilet, researchers said.

The disinfectant/brush combo reduced viral contamination on the toilet by nearly 100%, and on the brush by about 98%, results show.

Adding disinfectant to the bowl before flushing or using disinfectant dispensers in the toilet tank both proved effective in reducing contamination from flushing.

“In healthcare settings, any potential means of pathogen transmission must be addressed to keep all of our patients — including the most vulnerable, such as immunocompromised individuals — as healthy as possible,” Gerba said.

Closing the toilet lid did alter the direction of the aerosol plume, researchers found. The floor in front of and to the left of the toilet were more contaminated after flushing with a closed lid than with an open lid.

Given all this, regularly disinfecting the toilet could help reduce the spread of an infection to other people in a household where someone’s battling a viral infection, researchers said.

“This study helps establish a clearer understanding of how pathogens spread and the measures we can take to break those chains of transmission,” Tania Bubb, president of the Association for Professionals in Infection Control and Epidemiology, said in an association news release. “It also underscores the importance of regular disinfection of surfaces in healthcare settings for reducing the spread of viral infections.”

https://www.upi.com/Health_News/2024/01/25/closing-toilet-lid-germ-spread/9681706196547

New study concludes diabetes and weight-loss drugs—Ozempic and Wegovy—not associated with increased risk for suicidal thoughts

A new study by researchers at Case Western Reserve University School of Medicine reveals that a chemical used in the diabetes drug Ozempic and the weight-management drug Wegovy is not associated with an increased risk for suicidal thoughts.

The findings about the chemical—known as semaglutide—is particularly significant because this summer the European Medicines Agency (EMA) launched an investigation of its potential dangers.

Semaglutide is a chemical of the glucagon-like peptide receptor (GLP1R) that helps regulate blood sugar in type 2 diabetes and reduces appetite.

After examining about 2 million patients with type 2 diabetes or obesity, the research team­—led by biomedical informatics professor Rong Xu—found no evidence to support the EMA’s concern that semaglutide may cause suicidal ideations.

In fact, the study, recently published in the peer-reviewed journal Nature Medicine, found that Ozempic and Wegovy actually reduced the risk for suicidal ideations.

Xu, also the director of the medical school’s Center for AI in Drug Discovery, was joined by medical school co-authors, Nathan Berger, the Hanna-Payne Professor of Experimental Medicine, and Pamela B. Davis, the Arline H. and Curtis F. Garvin Research Professor. Nora D. Volkow, director of the National Institute for Drug Abuse, also was a co-author.

To assess the association of semaglutide and the risk of suicidal ideations, the team began examining electronic health records of nearly 101 million patients nationally. They then applied specific inclusion criteria to further select 2 million patients.

“It was similar to how we gathered real-time evidence of COVID-19 infections and outcomes during the COVID-19 pandemic,” Xu said.

Berger added that a clinical trial will be necessary to fully understand the side effects of semaglutide. In the meantime, the group has been able to analyze national data to help patients make educated decisions about the risk of using semaglutide.

In this study, two distinct patient populations were analyzed: Those with type 2 diabetes were provided Ozempic, while patients with obesity were prescribed Wegovy. Patients were tracked for six months to evaluate the occurrence of suicidal ideation as well as any recurrent suicidal thoughts, as recorded in their health records.

Men and women; Black, White and Hispanic patients; adults under 45; middle-aged adults (46–64); and elderly patients (65 years and older) also underwent separate examinations. Once more, the researchers reported, reductions in the risk of suicidal ideation were consistently found across age, ethnicity and gender.  

When compared to non-GLP1R anti-obesity and anti-diabetes drugs, it showed a lower risk for both the first incidence and recurrence of suicidal ideations in patients who were prescribed semaglutide (as Ozempic or Wegovy).

“The exploding popularity of this drug makes it imperative to understand all its potential complications,” Davis said. “It’s important to know that prior suggestions that the drug might trigger suicidal thoughts is not borne out in this very large and diverse population in the U.S.”

New insights into electroconvulsive therapy, a stigmatized yet highly effective treatment for depression

When most people hear about electroconvulsive therapy, or ECT, it typically conjures terrifying images of cruel, outdated and pseudo-medical procedures. Formerly known as electroshock therapy, this perception of ECT as dangerous and ineffective has been reinforced in pop culture for decades – think the 1962 novel-turned-Oscar-winning film “One Flew Over the Cuckoo’s Nest,” where an unruly patient is subjected to ECT as punishment by a tyrannical nurse.

Despite this stigma, ECT is a highly effective treatment for depression – up to 80% of patients experience at least a 50% reduction in symptom severity. For one of the most disabling illnesses around the world, I think it’s surprising that ECT is rarely used to treat depression.

Contributing to the stigma around ECT, psychiatrists still don’t know exactly how it heals a depressed person’s brain. ECT involves using highly controlled doses of electricity to induce a brief seizure under anesthesia. Often, the best description you’ll hear from a physician on why that brief seizure can alleviate depression symptoms is that ECT “resets” the brain – an answer that can be fuzzy and unsettling to some.

As a data-obsessed neuroscientist, I was also dissatisfied with this explanation. In our newly published research, my colleagues and I in the lab of Bradley Voytek at UC San Diego discovered that ECT might work by resetting the brain’s electrical background noise.

Listening to brain waves

To study how ECT treats depression, my team and I used a device called an electroencephalogram, or EEG. It measures the brain’s electrical activity – or brain waves – via electrodes placed on the scalp. You can think of brain waves as music played by an orchestra. Orchestral music is the sum of many instruments together, much like EEG readings are the sum of the electrical activity of millions of brain cells.

Two types of electrical activity make up brain waves. The first, oscillations, are like the highly synchronized, melodic music you might hear in a symphony. The second, aperiodic activity, is more like the asynchronous noise you hear as musicians tune their instruments. These two types of activities coexist in the brain, together creating the electrical waves an EEG records.

Importantly, tuning noises and symphonic music shouldn’t be mistaken for one another. They clearly come from different processes and serve different purposes. The brain is similar in this way – aperiodic activity and oscillations are different because the biology driving them is distinct.

Diagram showing EEG reading of neural oscillations and aperiodic activity
This diagram shows two EEG readings: One signal contains slow neural oscillations and the other contains only aperiodic activity. Although these signals can be tricky to visually distinguish, certain data analysis methods can help tease them apart. Sydney Smith, CC BY-ND

However, the methods neuroscientists have traditionally used to analyze these signals are unable to differentiate between the oscillations (symphony) and the aperiodic activity (tuning). Both are critical for the orchestra, but so far neuroscientists have mostly ignored – or entirely missed – aperiodic signals because they were thought to be just the brain’s background noise.

In our new research, my team and I show that ignoring aperiodic brain activity likely explains the confusion behind about how ECT treats depression. It turns out we’ve been missing this signal all along.

Connecting aperiodic activity and ECT

Since the 1940s, ECT has been associated with increases in slow oscillations in the brain waves of patients. However, those slow oscillations have never been linked to how ECT works. The degree to which slow oscillations appear is not consistently related to how much symptoms improve following ECT. Nor have ideas about how the brain produces slow oscillations connected those processes to the pathology underlying depression.

Because these two types of brain waves are difficult to separate in measurements, I wondered if these slow oscillations were in fact incorrectly measured aperiodic activity. Returning to our orchestra analogy, I believed that scientists had misidentified the tuning sounds as symphony music.

To investigate this, my team and I gathered three EEG datasets: one from nine patients with depression undergoing ECT in San Diego, another from 22 patients in Toronto receiving ECT and a third from 22 patients in Toronto participating in a clinical trial of magnetic seizure therapy, or MST, a newer alternative to ECT that starts a seizure with magnets instead of electricity.

We found that aperiodic activity increases by more than 40% on average following ECT. In patients who received MST treatment, aperiodic activity increases more modestly, by about 16%. After accounting for changes in aperiodic activity, we found that slow oscillations do not change much at all. In fact, slow oscillations were not even detected in some patients, and aperiodic activity dominated their EEG recordings instead.

How ECT treats depression

But what does aperiodic activity have to do with depression?

A long-standing theory of depression states that severely depressed patients have too few of a type of brain cell called inhibitory cells. These cells can turn other brain cells on and off, and maintaining the balance of these on and off states is critical for healthy brain function. This balance is particularly relevant for depression because the brain’s ability to turn cells off plays an important role in how it responds to stress, a function that, when not working properly, makes people particularly vulnerable to depression.

Using a mathematical model of cell type-based electrical activity, I linked increases in aperiodic activity, like those seen in the ECT patients, to a huge change in the activity of these inhibitory cells. This change in aperiodic activity may be restoring the crucial on and off balance in the brain to a healthy level.

Even though scientists have been recording EEGs from ECT patients for decades, this is the first time that brain waves have been connected to this particular brain malfunction.

Altogether, though our sample size is relatively small, our findings indicate that ECT and MST likely treat depression by resetting aperiodic activity and restoring the function of inhibitory brain cells. Further study can help destigmatize ECT and highlight new directions for the research and development of depression treatments. Listening to the nonmusical background noise of the brain could help solve other mysteries, like how the brain changes in aging and in illnesses like schizophrenia and epilepsy.

https://theconversation.com/how-electroconvulsive-therapy-heals-the-brain-new-insights-into-ect-a-stigmatized-yet-highly-effective-treatment-for-depression-217889

New research from UC Davis explains why red wine causes headaches

A study from UC Davis suggests that quercetin, a flavanol in red wine, could cause headaches by disrupting alcohol metabolism and leading to toxin buildup. Further research is planned to understand why some people are more susceptible to these headaches.

Not everyone feels fine after red wine, and a flavanol may be the culprit.

A red wine may pair nicely with the upcoming Thanksgiving meal. But for some people, drinking red wine even in small amounts causes a headache. Typically, a “red wine headache” can occur within 30 minutes to three hours after drinking as little as a small glass of wine.

What in Wine Causes Headaches?

In a new study, scientists at the University of California, Davis, examined why this happens – even to people who don’t get headaches when drinking small amounts of other alcoholic beverages. Researchers think that a flavanol found naturally in red wines can interfere with the proper metabolism of alcohol and can lead to a headache. The study was published on November 20 in the journal Scientific Reports.

The Headache Culprit: Quercetin, a Flavanol

This flavanol is called quercetin and it is naturally present in all kinds of fruits and vegetables, including grapes. It’s considered a healthy antioxidant and is even available in supplement form. But when metabolized with alcohol, it can be problematic.

“When it gets in your bloodstream, your body converts it to a different form called quercetin glucuronide,” said wine chemist and corresponding author Andrew Waterhouse, professor emeritus with the UC Davis Department of Viticulture and Enology. “In that form, it blocks the metabolism of alcohol.”

Acetaldehyde Toxin Buildup Leads to Flushing, Headache, Nausea

As a result, people can end up accumulating the toxin acetaldehyde, explains lead author Apramita Devi, postdoctoral researcher with the UC Davis Department of Viticulture and Enology.

“Acetaldehyde is a well-known toxin, irritant, and inflammatory substance,” said Devi. “Researchers know that high levels of acetaldehyde can cause facial flushing, headache, and nausea.”

The medication disulfiram prescribed to alcoholics to prevent them from drinking causes these same symptoms. Waterhouse said that’s because the drug also causes the toxin to build up in the body when normally an enzyme in the body would break it down. About 40% of the East Asian population also has an enzyme that doesn’t work very well, allowing acetaldehyde to build up in their system.

“We postulate that when susceptible people consume wine with even modest amounts of quercetin, they develop headaches, particularly if they have a preexisting migraine or another primary headache condition,” said co-author Morris Levin, professor of neurology and director of the Headache Center at the University of California, San Francisco. “We think we are finally on the right track toward explaining this millennia-old mystery. The next step is to test it scientifically on people who develop these headaches, so stay tuned.”

Sunlight Increases Headache-Causing Flavanol in Grapes

Waterhouse said levels of this flavanol can vary dramatically in red wine.

“Quercetin is produced by the grapes in response to sunlight,” Waterhouse said. “If you grow grapes with the clusters exposed, such as they do in the Napa Valley for their cabernets, you get much higher levels of quercetin. In some cases, it can be four to five times higher.”

Levels of quercetin can also differ depending on how the wine is made, including skin contact during fermentation, fining processes, and aging.

Clinical Trial on Wine Headaches

Scientists will next compare red wines that contain a lot of quercetin with those that have very little to test their theory about red wine headaches on people. This small human clinical trial, funded by the Wine Spectator Scholarship Foundation, will be led by UCSF.

Researchers said there are still many unknowns about the causes of red wine headaches. It’s unclear why some people seem more susceptible to them than others. Researchers don’t know if the enzymes of people who suffer from red wine headaches are more easily inhibited by quercetin or if this population is just more easily affected by the buildup of the toxin acetaldehyde.

“If our hypothesis pans out, then we will have the tools to start addressing these important questions,” Waterhouse said.

Reference: “Inhibition of ALDH2 by quercetin glucuronide suggests a new hypothesis to explain red wine headaches” by Apramita Devi, Morris Levin and Andrew L. Waterhouse, 20 November 2023, Scientific Reports.
DOI: 10.1038/s41598-023-46203-y

Funding for this initial investigation came from people who supported the project via 2022 Crowdfund UC Davis.