Discovery could explain why women are more likely to get Alzheimer's

December 14, 2022

Science Daily/Scripps Research Institute

Scientists at Scripps Research and Massachusetts Institute of Technology (MIT) have found a clue to the molecular cause of Alzheimer's -- a clue that may also explain why women are at greater risk for the disease.

In the study, reported on December 14, 2022, in Science Advances, the researchers found that a particularly harmful, chemically modified form of an inflammatory immune protein called complement C3 was present at much higher levels in the brains of women who had died with the disease, compared to men who had died with the disease. They also showed that estrogen -- which drops in production during menopause -- normally protects against the creation of this form of complement C3.

"Our new findings suggest that chemical modification of a component of the complement system helps drive Alzheimer's, and may explain, at least in part, why the disease predominantly affects women," says study senior author Stuart Lipton, MD, PhD, professor and Step Family Foundation Endowed Chair in the Department of Molecular Medicine at Scripps Research and a clinical neurologist in La Jolla, California.

The study was a collaboration with a team led by Steven Tannenbaum, PhD, Post Tenure Underwood-Prescott Professor of Biological Engineering, Chemistry and Toxicology at MIT.

Alzheimer's, the most common form of dementia that occurs with aging, currently afflicts about six million people in the U.S. alone. It is always fatal, usually within a decade of onset, and there is no approved treatment that can halt the disease process, let alone reverse it. The shortcomings of treatments reflect the fact that scientists have never fully understood how Alzheimer's develops. Scientists also don't know fully why women account for nearly two-thirds of cases.

Lipton's lab studies biochemical and molecular events that may underlie neurodegenerative diseases, including the chemical reaction that forms a modified type of complement C3 -- a process called protein S-nitrosylation. Lipton and his colleagues previously discovered this chemical reaction, which happens when a nitric oxide (NO)-related molecule binds tightly to a sulfur atom (S) on a particular amino acid building-block of proteins to form a modified "SNO-protein." Protein modifications by small clusters of atoms such as NO are common in cells and typically activate or deactivate a target protein's functions. For technical reasons, S-nitrosylation has been more difficult to study than other protein modifications, but Lipton suspects that "SNO-storms" of these proteins could be a key contributor to Alzheimer's and other neurodegenerative disorders.

For the new study, the researchers used novel methods for detecting S-nitrosylation to quantify proteins modified in 40 postmortem human brains. Half of the brains were from people who had died of Alzheimer's, and half were from people who hadn't -- and each group was divided equally between males and females.

In these brains, the scientists found 1,449 different proteins that had been S-nitrosylated. Among the proteins most often modified in this way, there were several that have already been tied to Alzheimer's, including complement C3. Strikingly, the levels of S-nitrosylated C3 (SNO-C3) were more than six-fold higher in female Alzheimer's brains compared to male Alzheimer's brains.

The complement system is an evolutionarily older part of the human immune system. It consists of a family of proteins, including C3, that can activate one another to drive inflammation in what is called the "complement cascade." Scientists have known for more than 30 years that Alzheimer's brains have higher levels of complement proteins and other markers of inflammation, compared to neurologically normal brains. More recent research has shown specifically that complement proteins can trigger brain-resident immune cells called microglia to destroy synapses -- the connection points through which neurons send signals to one another. Many researchers now suspect that this synapse-destroying mechanism at least partly underlies the Alzheimer's disease process, and loss of synapses has been demonstrated to be a significant correlate of cognitive decline in Alzheimer's brains.

Why would SNO-C3 be more common in female brains with Alzheimer's? There has long been evidence that the female hormone estrogen can have brain-protective effects under some conditions; thus, the researchers hypothesized that estrogen specifically protects women's brains from C3 S-nitrosylation -- and this protection is lost when estrogen levels fall sharply with menopause. Experiments with cultured human brain cells supported this hypothesis, revealing that SNO-C3 increases as estrogen (?-estradiol) levels fall, due to the activation of an enzyme that makes NO in brain cells. This increase in SNO-C3 activates microglial destruction of synapses.

"Why women are more likely to get Alzheimer's has long been a mystery, but I think our results represent an important piece of the puzzle that mechanistically explains the increased vulnerability of women as they age," Lipton says.

He and his colleagues now hope to conduct further experiments with de-nitrosylating compounds -- which remove the SNO modification -- to see if they can reduce pathology in animal models of Alzheimer's and eventually in humans.

https://www.sciencedaily.com/releases/2022/12/221214180658.htm

Not-so private eyes: Eye movements hold clues to how we make decisions

December 13, 2022

Science Daily/University of Colorado at Boulder

New research led by scientists at the University of Colorado Boulder suggests that eyes may really be the window to the soul -- or, at least, how humans dart their eyes may reveal valuable information about how they make decisions.

The new findings offer researchers a rare opportunity in neuroscience: the chance to observe the inner workings of the human brain from the outside. Doctors could also potentially use the results to, one day, screen their patients for illnesses like depression or Parkinson's Disease.

"Eye movements are incredibly interesting to study," said Colin Korbisch, doctoral student in the Paul M. Rady Department of Mechanical Engineering at CU Boulder and lead author of the study. "Unlike your arms or legs, the speed of eye movements is almost totally involuntary. It's a much more direct measurement of these unconscious processes happening in your brain."

He and his colleagues, including researchers at Johns Hopkins University in Baltimore, published their findings in November in the journal Current Biology.

In the study, the team asked 22 human subjects to walk on a treadmill then choose between different settings displayed on a computer screen: a brief walk up a steep grade or a longer walk on flat ground.

Researchers discovered that the subjects' eyes gave them away: Even before they made their choices, the treadmill users tended to move their eyes faster when they looked toward the options they ended up choosing. The more vigorously their eyes moved, the more they seemed to prefer their choice.

"We discovered an accessible measurement that will tell you, in only a few seconds, not just what you prefer but how much you prefer it," said Alaa Ahmed, senior author of the study and associate professor of mechanical engineering at CU Boulder.

Shifty eyes

Ahmed explained that how or why humans make choices (Tea or coffee? Dogs or cats?) is notoriously difficult to study. Researchers don't have many tools that will easily allow them to peer inside the brain. Ahmed, however, believes that our eyes could provide a glimpse into some of our thought processes. She's particularly interested in a type of movement known as a "saccade."

"The primary way our eyes move is through saccades," Ahmed said. "That's when your eyes quickly jump from one fixation point to another."

Quickly is the key word: Saccades usually take just a few dozen milliseconds to complete, making them faster than an average blink.

To find out if these darting motions give clues about how humans come to decisions, Ahmed and her colleagues decided to hit the gym.

In the new study, the team set up a treadmill on the CU Boulder campus. Study subjects exercised on various inclines for a period of time then sat down in front of a monitor and a high-speed, camera-based device that tracked their eye movements. While at the screen, they pondered a series of options, getting 4 seconds to pick between two choices represented by icons: Did they want to walk for 2 minutes at a 10% grade or for 6 minutes at a 4% grade? Once done, they returned to the treadmill to feel the burn based on what they chose.

The team found that subjects' eyes underwent a marathon of activity in just a short span of time. As they considered their options, the individuals flitted their eyes between the icons, first slowly and then faster.

"Initially, the saccades to either option were similarly vigorous," Ahmed said. "Then, as time passed, that vigor increased and it increased even faster for the option they eventually chose."

The researchers also discovered that people who made the hastiest decisions -- the most impulsive members of the group, perhaps -- also tended to move their eyes more vigorously. Once the subjects decided on their pick, their eyes slowed again.

"Real-time read-outs of this decision-making process typically require invasive electrodes placed into the brain. Having this more easily measured variable opens a lot of possibilities," Korbisch said.

Diagnosing illness

Flicks of the eye could matter for a lot more than understanding how humans make decisions. Studies in monkeys, for example, have suggested that some of the same pathways in the brain that help primates pick between this or that may also break down in people with Parkinson's -- a neurological illness in which individuals experience tremors, difficulty moving and other issues.

"Slowed movements aren't just a symptom of Parkinson's but also appear in a lot of mental health disorders, such as depression and schizophrenia," Ahmed said. "We think these eye movements could be something that medical professionals track as a diagnostic tool, a way to identify the progress of certain illnesses."

Eyes, in other words, could be windows to a lot more than just the soul.

https://www.sciencedaily.com/releases/2022/12/221213094812.htm

A Mediterranean diet not only boosts health, but also improves fertility

December 13, 2022

Science Daily/University of South Australia

With an emphasis on fruits, vegetables and legumes, the Mediterranean diet has long been applauded for its multiple health benefits. Now, new research shows that it may also help overcome infertility, making it a non-intrusive and affordable strategy for couples trying to conceive.

Conducted by Monash University, the University of the Sunshine Coast, and the University of South Australia, the review found that the Mediterranean diet can improve fertility, assisted reproductive technology (ART) success, and sperm quality in men.

Specifically, researchers identified that the anti-inflammatory properties of a Mediterranean diet can improve couples' chances of conception.

Infertility is a global health concern affecting 48 million couples and 186 million individuals worldwide.

UniSA researcher, Dr Evangeline Mantzioris, says modifying preconception nutrition is a non-invasive and potentially effective means for improving fertility outcomes.

"Deciding to have a baby is one of life's biggest decisions, but if things don't go as planned, it can be very stressful for both partners," Dr Mantzioris says.

"Research shows inflammation can affect fertility for both men and women, affecting sperm quality, menstrual cycles, and implantation. So, in this study we wanted to see how a diet that reduces inflammation -- such as the Mediterranean diet -- might improve fertility outcomes.

"Encouragingly, we found consistent evidence that by adhering to an anti-inflammatory diet -- one that includes lots of polyunsaturated or 'healthy' fats, flavonoids (such as leafy green vegetables), and a limited amount of red and processed meat -- we can improve fertility."

The Mediterranean diet is primarily plant-based, and includes whole grains, extra virgin olive oil, fruits, vegetables, beans and legumes, nuts, herbs, and spices. Yoghurt, cheese, and lean protein sources such as fish, chicken, or eggs; red and processed meats are only eaten in small amounts.

In comparison, a western diet comprises excessive saturated fats, refined carbohydrates, and animal proteins, making it energy-dense and lacking dietary fibre, vitamins, and minerals. Typically, a western diet is associated with higher levels of inflammation.

Monash University researcher, Simon Alesi, says understanding the association between anti-inflammatory diets such as the Mediterranean diet, and fertility, could be a gamechanger for couples hoping to start a family.

"The Mediterranean diet is consistently ranked among the healthiest diets in the world. But knowing that it may also boost your chances of conceiving and having a baby is extremely promising," Alesi says.

"Modifying your diet is a non-intrusive and affordable strategy that could potentially improve infertility.

"Of course, more research needs to be done, but at the very least, shifting to a Mediterranean diet will not only improve your overall health, but also your chances of conceiving."

https://www.sciencedaily.com/releases/2022/12/221213094801.htm

Extremely hot and cold days linked to cardiovascular deaths

December 12, 2022

Science Daily/American Heart Association

Extremely hot and cold temperatures both increased the risk of death among people with cardiovascular diseases, such as ischemic heart disease (heart problems caused by narrowed heart arteries), stroke, heart failure and arrhythmia, according to new research published today in the American Heart Association's flagship journal Circulation.

Among the cardiovascular diseases examined in this study, heart failure was linked to the highest excess deaths from extreme hot and cold temperatures.

"The decline in cardiovascular death rates since the 1960s is a huge public health success story as cardiologists identified and addressed individual risk factors such as tobacco, physical inactivity, Type 2 diabetes, high blood pressure and others. The current challenge now is the environment and what climate change might hold for us," said Barrak Alahmad, M.D., M.P.H., Ph.D., research fellow at the Harvard T.H. Chan School of Public Health at Harvard University in Boston and a faculty member at the College of Public Health at Kuwait University in Kuwait City.

Researchers explored how extreme temperatures may affect heart diseases -- the leading cause of death globally. They analyzed health data for more than 32 million cardiovascular deaths that occurred in 567 cities in 27 countries on 5 continents between 1979 and 2019. The global data came from the Multi-Country Multi-City (MCC) Collaborative Research Network, a consortium of epidemiologists, biostatisticians and climate scientists studying the health impacts of climate and related environmental stressors on death rates.

Climate change is associated with substantial swings in extreme hot and cold temperatures, so the researchers examined both in the current study. For this analysis, researchers compared cardiovascular deaths on the hottest and the coldest 2.5% of days for each city with cardiovascular deaths on the days that had optimal temperature (the temperature associated with the least rates of deaths) in the same city.

For every 1,000 cardiovascular deaths, the researchers found that:

• Extreme hot days accounted for 2.2 additional deaths.

• Extreme cold days accounted for 9.1 additional deaths.

• Of the types of heart diseases, the greatest number of additional deaths was found for people with heart failure (2.6 additional deaths on extreme hot days and 12.8 on extreme cold days).

"One in every 100 cardiovascular deaths may be attributed to extreme temperature days, and temperature effects were more pronounced when looking at heart failure deaths," said Haitham Khraishah, M.D., co-author of the study and a cardiovascular disease fellow at the University of Maryland School of Medicine and the University of Maryland Medical Center in Baltimore. "While we do not know the reason, this may be explained by the progressive nature of heart failure as a disease, rendering patients susceptible to temperature effects. This is an important finding since one out of four people with heart failure are readmitted to the hospital within 30 days of discharge, and only 20% of patients with heart failure survive 10 years after diagnosis."

Researchers suggest targeted warning systems and advice for vulnerable people may be needed to prevent cardiovascular deaths during temperature extremes.

"We need to be on top of emerging environmental exposures. I call upon the professional cardiology organizations to commission guidelines and scientific statements on the intersection of extreme temperatures and cardiovascular health. In such statements, we may provide more direction to health care professionals, as well as identify clinical data gaps and future priorities for research," Alahmad said.

The underrepresentation of data from South Asia, the Middle East and Africa limits the ability to apply these findings to make global estimates about the impact of extreme temperatures on cardiovascular deaths.

"This study contributes important information to the ongoing societal discussions regarding the relationship between climate and human health. More work is needed to better define these relationships in a world facing climate changes across the globe in the years ahead, especially as to how those environmental changes might impact the world's leading cause of death and disability, heart disease," said AHA Past President Robert A. Harrington, M.D., FAHA, who is the Arthur L. Bloomfield Professor of Medicine and chair of the department of medicine at Stanford University.

https://www.sciencedaily.com/releases/2022/12/221212140743.htm

Trouble falling asleep at night? Chase that daytime light

December 12, 2022

Science Daily/University of Washington

A study measuring the sleep patterns of students at the University of Washington has turned up some surprises about how and when our bodies tell us to sleep -- and illustrates the importance of getting outside during the day, even when it's cloudy.

Published online Dec. 7 in the Journal of Pineal Research, the study found that UW students fell asleep later in the evening and woke up later in the morning during -- of all seasons -- winter, when daylight hours on the UW's Seattle campus are limited and the skies are notoriously overcast.

The team behind this study believes it has an explanation: The data showed that in winter students received less light exposure during the day. Other research has indicated that getting insufficient light during the day leads to problems at night, when it's time for bed.

"Our bodies have a natural circadian clock that tells us when to go to sleep at night," said senior author Horacio de la Iglesia, a UW professor of biology. "If you do not get enough exposure to light during the day when the sun is out, that 'delays' your clock and pushes back the onset of sleep at night."

The study used wrist monitors to measure sleep patterns and light exposure for 507 UW undergraduate students from 2015 to 2018. Data indicated that students were getting roughly the same amount of sleep each night regardless of season. But, on school days during the winter, students were going to bed on average 35 minutes later and waking up 27 minutes later than summer school days. This finding surprised the team, since Seattle -- a high-latitude city -- receives nearly 16 hours of sunlight on the summer solstice, with plenty evening light for social life, and just over eight hours of sunlight on the winter solstice.

"We were expecting that in the summer students would be up later due to all the light that's available during that season," said de la Iglesia.

Based on student sleep data, the researchers hypothesized that something in winter was "pushing back" the students' circadian cycles. For most humans, including college students, the innate circadian cycle governing when we're awake and asleep runs at about 24 hours and 20 minutes -- and is "calibrated" daily by input from our environment. For UW students in the study, sleep data indicated that their circadian cycles were running up to 40 minutes later in winter compared to summer.

The team focused on light as a potential explanation for this winter delay. But light has different impacts on circadian rhythms at different times of the day.

"Light during the day -- especially in the morning -- advances your clock, so you get tired earlier in the evening, but light exposure late in the day or early night will delay your clock, pushing back the time that you will feel tired," said de la Iglesia. "Ultimately, the time that you fall asleep is a result of the push and pull between these opposite effects of light exposure at different times of the day."

Data showed that daytime light exposure had a greater impact than evening light exposure in the UW study. Each hour of daytime light "moved up" the students' circadian phases by 30 minutes. Even outdoor light exposure on cloudy or overcast winter days in Seattle had this effect, since that light is still significantly brighter than artificial indoor lighting, said de la Iglesia. Each hour of evening light -- light from indoor sources like lamps and computer screens -- delayed circadian phases by an average of 15 minutes.

"It's that push-and-pull effect," said de la Iglesia. "And what we found here is that since students weren't getting enough daytime light exposure in the winter, their circadian clocks were delayed compared to summer."

The study offers lessons not just for college students.

"Many of us live in cities and towns with lots of artificial light and lifestyles that keep us indoors during the day," said de la Iglesia. "What this study shows is that we need to get out -- even for a little while and especially in the morning -- to get that natural light exposure. In the evening, minimize screen time and artificial lighting to help us fall asleep."

https://www.sciencedaily.com/releases/2022/12/221212140707.htm

Unraveling the secrets of a good night's sleep

December 12, 2022

Science Daily/University of Tsukuba

A good night's sleep can work wonders for both mind and body. But what is it that determines how much we need to sleep, and what can cause us to sleep more deeply? In a new study, researchers from the University of Tsukuba have now provided some answers, revealing a signaling pathway within brain cells that regulates the length and depth of sleep.

"We examined genetic mutations in mice and how these affect their patterns of sleep," says senior author of the study, Professor Hiromasa Funato. "We identified a mutation that led to the mice sleeping much longer and more deeply than usual." The researchers found that this was caused by low levels of an enzyme called histone deacetylase 4 (HDAC4), which is known to suppress the expression of target genes.

Previous studies on HDAC4 have shown that it is greatly affected by the attachment of phosphate molecules in a process known as phosphorylation. When this occurs, HDAC4 tends to move away from the cell nucleus, and the suppression of certain proteins is reduced. The researchers were interested in whether this phosphorylation of HDAC4 would affect sleep.

"We focused on a protein called salt-inducible kinase 3, otherwise known as SIK3, which phosphorylates HDAC4," says Professor Funato. "We previously found that this protein has strong effects on sleep." The team found that when there was a lack of SIK3 or when HDAC4 was modified to prevent phosphorylation, the mice slept less. In contrast, when the mice had a more active version of SIK3, which increased the phosphorylation of HDAC4, they slept a lot more. They also identified a further protein, LKB1, which phosphorylates SIK3, and has similar sleep-suppressing effects when deficient.

"Our findings indicate that there is a signaling pathway within brain cells from LKB1 to SIK3 and then to HDAC4," says study co-senior author, Professor Masashi Yanagisawa. "This pathway leads to the phosphorylation of HDAC4, which promotes sleep, most probably because it affects the expression of sleep-promoting genes."

The team carried out further experiments to identify the brain cells in which these pathways regulate sleep. This involved altering the amounts of SIK3 and HDAC4 in different cell types and brain regions. The results indicated that signaling within the cells of the cortex regulates the depth of sleep, while signaling within the hypothalamus regulates the amount of deep sleep. For both brain regions, the excitatory neurons, which can activate other neurons, were identified as playing a key role.

These results provide an important insight into how sleep is regulated, which could potentially lead to a greater understanding of sleep disorders as well as the development of new treatments.

https://www.sciencedaily.com/releases/2022/12/221212140635.htm

Light therapy relieves fatigue syndrome in Multiple Sclerosis

December 12, 2022

Science Daily/Medical University of Vienna

Multiple Sclerosis (MS) is almost always accompanied by fatigue, a massive tiredness that is described by the vast majority of patients as the most distressing symptom. In a recent scientific study, a research group led by Stefan Seidel from the Department of Neurology at MedUni Vienna and AKH Vienna identified light therapy as a promising non-drug treatment option: patients included in the study showed a measurable improvement after just 14 days of use. The study results were recently published in the Multiple Sclerosis Journal -- Experimental, Translational and Clinical.

For the first time, Stefan Seidel's research team relied not only on surveys but also on objective measurements when selecting the test persons. For example, sleep-wake disorders were ruled out in the 26 participating MS patients, particularly with the assistance of various sleep medicine examinations. "In this manner, for example, we ensured that MS patients with fatigue do not suffer from sleep apnea or periodic leg movements during sleep. Both are sleep disorders that can lead to fatigue in everyday life," elaborated study leader Stefan Seidel.

Performance improvement

The test persons -- all patients of the Neurology Department at MedUni Vienna and AKH Vienna -- were equipped with commercially available light sources for self-testing at home: Half of the participants received a daylight lamp with a brightness of 10,000 lux, while the other half received an identical lamp that emitted a red light with an intensity of <300 lux due to a filter. While the red light used by the control group showed no effect, the researchers were able to observe measurable successes in the other group after only 14 days: The participants who used their 10,000 lux daylight lamp for half an hour every day showed improved physical and mental performance after only a short period of time. In addition, the group of participants who had consumed bright light displayed less daytime sleepiness in comparison with the other group.

Up to 99 percent of patients

Fatigue is a severe form of tiredness and fatigability that occurs in 75 to 99 percent of people with MS and is described as particularly distressing. Nerve damage triggered by MS is being discussed as the cause. In addition to behavioural measures, such as regular rest breaks, various medications are currently available to alleviate fatigue, but some of these are associated with severe side effects. "The findings from our study represent a promising non-drug therapeutic approach," Stefan Seidel affirms. However, the results still need to be confirmed in a subsequent larger-scale study. The exact background of the invigorating effect of light therapy on MS patients will also be the subject of further scientific research.

https://www.sciencedaily.com/releases/2022/12/221212140501.htm

Adding yoga to regular exercise improves cardiovascular health and wellbeing

December 8, 2022

Science Daily/Elsevier

A three-month pilot study of patients with hypertension appearing in the Canadian Journal of Cardiology, published by Elsevier, demonstrates that adding yoga to a regular exercise training https://www.sciencedaily.com/releases/2022/12/221208123538.htmregimen supports cardiovascular health and wellbeing and is more effective than stretching exercises. Incorporation of yoga reduced systolic blood pressure and resting heart rate and improved 10-year cardiovascular risk.

Yoga is part of spiritual and exercise practices for millions of people worldwide. With yoga practice becoming a widely accepted form of exercise, the body of yoga research is growing. It is a multifaceted lifestyle activity that can positively enhance cardiovascular health and wellbeing. Physical exercises such as stretching exercises and the physical components of yoga practices have several similarities, but also important differences.

"The aim of this pilot study was to determine whether the addition of yoga to a regular exercise training regimen reduces cardiovascular risk," explained lead investigator Paul Poirier, MD, PhD, Quebec Heart and Lung Institute -- Laval University, and Faculty of Pharmacy, Laval University, Quebec, Canada. "While there is some evidence that yoga interventions and exercise have equal and/or superior cardiovascular outcomes, there is considerable variability in yoga types, components, frequency, session length, duration, and intensity. We sought to apply a rigorous scientific approach to identify cardiovascular risk factors for which yoga is beneficial for at-risk patients and ways it could be applied in a healthcare setting such as a primary prevention program."

Investigators recruited 60 individuals with previously diagnosed high blood pressure and metabolic syndrome for an exercise training program. Over the 3-month intervention regimen, participants were divided into 2 groups, which performed 15 minutes of either structured yoga or stretching in addition to 30 minutes of aerobic exercise training 5 times weekly. Blood pressure, anthropometry, high-sensitivity C-reactive protein (hs-CRP), glucose and lipids levels as well as the Framingham and Reynolds Risk Scores were measured. At baseline, there was no difference between groups in age, sex, smoking rates, body mass index (BMI), resting systolic and diastolic blood pressure, resting heart rate and pulse pressure.

After 3 months, there was a decrease in resting systolic and diastolic blood pressure, mean arterial blood pressure and heart rate in both groups. However, systolic blood pressure was reduced by 10 mmHg with yoga vs 4 mmHg with stretching. The yoga approach also reduced resting heart rate and 10-year cardiovascular risk assessed using Reynold's Risk score.

While yoga has been shown to benefit hypertensive patients, the exact mechanism underlying this positive effect is not fully understood. This pilot randomized study shows that its benefits cannot be simply attributed to stretching alone.

"This study provides evidence for an additional non-pharmacologic therapy option for cardiovascular risk reduction and blood pressure control in patients with high blood pressure, in the setting of a primary prevention exercise program," noted Dr. Poirier. "As observed in several studies, we recommend that patients try to find exercise and stress relief for the management of hypertension and cardiovascular disease in whatever form they find most appealing. Our study shows that structured yoga practices can be a healthier addition to aerobic exercise than simply muscle stretching."

https://www.sciencedaily.com/releases/2022/12/221208085826.htm

Co-working spaces limit creativity in the long run

Shared spaces can be inhibitors to new business collaborations, according to researchers

December 8, 2022

Science Daily/City University London

Co-working spaces can limit the creativity and innovation of new businesses, a study has found.

These shared spaces, which have boomed in popularity since the pandemic, may offer initial opportunities to collaborate but, before long, they ultimately inhibit the emergence of collaborative practices.

The study, co-authored by Bayes Business School, investigated how collaborative practices emerge in co-working spaces, using Level 39 -- a leading co-working space in the financial district in Canary Wharf, and one of the largest in Europe, which is mainly occupied by tech and fintech sectors -- as a base.

Findings show that the informal setting of the space initially supported collective explorations between start-ups but inhibited collaborations from developing.

While the space allowed for social interactions and networking in communal kitchen, lounge and breakout areas, findings showed that firms left the space as the collaborative benefits were small and interactions became less meaningful and stilted over time. Also, firms highlighted that the space became increasingly reliant on occupancy and scalability amid its growth which negatively impacted optimal special layout and more tailored relationships with start-ups.

Professor Stefan Haefliger, lead author and Bayes academic, conducted the research with former Bayes PhD student Ghassan Yacoub, and said the findings were of particular significance to managers and hosts of co-working spaces. He highlighted the need for a catalyst -- actors who facilitate and encourage activities that sustain interactions and encourage co-operation -- to drive impactful cross-working.

Professor Haefliger said: "The rise of co-working spaces as new forms of work has redefined our understanding of the traditional physical, temporal and spatial boundaries of organisations.

"It is the responsibility of the host of the space and those that use it to make it a setting that can see booming partnerships and a hotbed of next generation ideas. Entrepreneurs need to embrace the early-stage interactions to take the first step towards collaborative working, with workspace managers working as catalysts to drive these partnerships."

"Post pandemic we can expect more uncertainty in how space is re-appropriated by individuals and entrepreneurial teams forming collaboration. Workspace managers may need to leave room for experimentation and allow flexibility.

"The built environment represents a key strength and characteristic of Dubai and how, post-pandemic, work habits have changed, and how routines of collaboration might require updated spaces and interaction opportunities. How will a city like Dubai attract new work and cater to contemporary collaborative work? Dubai is both a hub for global collaboration and an experimental opportunity to drive change and inspire other global locations who might be slower to change."

https://www.sciencedaily.com/releases/2022/12/221208123538.htm

Researchers gain a better understanding of how the most commonly used ADHD medication works

December 8, 2022

Science Daily/Elsevier

For decades, doctors have treated kids with attention-deficit/hyperactivity disorder (ADHD) with methylphenidate, a stimulant drug sold as Ritalin and Concerta, making it one of the most widely prescribed medications aimed at the central nervous system. One might expect that researchers would know how methylphenidate works in the brain by now, but little is known about the drug's mechanism of action. Now, a new study seeks to close this gap and understand how methylphenidate interacts with cognitive control networks and attentional behavior.

The new study appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

What researchers do know is that individuals with ADHD have lower dopamine signaling activity than neurotypical individuals in the interconnected brain networks that control attention and goal-directed behaviors. Specifically, methylphenidate is hypothesized to ameliorate ADHD symptoms by increasing dopamine levels in the nucleus accumbens (NAc), a hub for dopamine signaling.

In the new study, researchers led by Yoshifumi Mizuno, MD, PhD, Weidong Cai, PhD, and Vinod Menon, PhD, used brain imaging to explore the effects of methylphenidate on the NAc and a so-called triple network system that plays a key role in behaviors that require adaptive control of attention. The three networks include the salience, frontoparietal, and default mode networks. Aberrant activity was detected in the NAc and in multiple brain networks in children with ADHD, suggesting that dysregulation in the system may underlie ADHD symptoms, and that correcting the dysfunction might alleviate those symptoms.

"Our findings demonstrate in two independent cohorts that methylphenidate changes spontaneous neural activity in reward and cognitive control systems in children with ADHD. Medication-induced changes in cognitive control networks result in more stable sustained attention. Our findings reveal a novel brain mechanism underlying methylphenidate treatment in ADHD and inform biomarker development for evaluating treatment outcomes," noted Dr. Menon, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine.

The researchers used functional magnetic resonance imaging (fMRI) to measure the effects of methylphenidate on spontaneous brain activity in 27 children with ADHD and 49 typically developing controls. Children with ADHD were scanned during two different visits one to six weeks apart -- once while receiving methylphenidate and once while receiving a placebo. (Typically developing children did not receive medication or placebo.) Outside the scanner, children with ADHD also performed a standardized task to assess sustained attention. Additionally, the researchers tested the replicability of methylphenidate's effects on spontaneous brain activity in a second independent cohort.

Not surprisingly, children performed better on the attention tasks when they were medicated. And as the researchers hypothesized, they also saw greater spontaneous neural activity in the NAc and the salience and default mode networks when methylphenidate was administered. Children with ADHD who displayed enhanced changes in brain activity patterns in the default mode network with medication performed better on the attention tasks with medication. Findings were replicated across two independent cohorts, providing further evidence that methylphenidate may alleviate ADHD symptoms by its actions on the NAc and the triple network cognitive system.

Cameron Carter, MD, editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the study, "The findings, which used the widely available technique of resting-state functional MRI, confirm the positive effects of methylphenidate on attention in children with ADHD and reveal the likely mechanism of action, through improved coordinated brain network activity and a likely key role for enhanced dopamine effects in the NAc region of the brain."

The work advances researchers' understanding of how ADHD affects cognitive control networks in the brain and how methylphenidate interacts with these networks to shift behavior. The findings could guide future work using brain imaging as a clinically useful biomarker of response to treatments.

https://www.sciencedaily.com/releases/2022/12/221208123533.htm

Fearlessness can be learned

December 5, 2022

Science Daily/Ruhr-University Bochum

The absence of a certain serotonin receptor supports the reduction of previously learned fear responses.

The neurotransmitter serotonin plays a key role in both the onset and in the unlearning of fear and anxiety. A research team from the Department of General Zoology and Neurobiology headed by Dr Katharina Spoida and Dr Sandra Süß in the Collaborative Research Centre "Extinction Learning" at Ruhr University Bochum, Germany, has been investigating the underlying mechanisms. The researchers showed that mice lacking a specific serotonin receptor unlearn fear much faster than the wild type. The results of the study provide a viable explanation how drugs that are typically used for the treatment of post-traumatic stress disorder (PTSD) alter our brain activity. The ability to unlearn fear is often impaired in PTSD patients, making it more difficult to carry out therapies. The study was published in the journal Translational Psychiatry on 19 November 2022.

Fear responses triggered by everyday sensory input

People who have been affected by a traumatic experience sometimes suffer from a long lasting exaggerated fear response. In such cases, the fear response is triggered by certain sensory impressions that occur in our everyday environment and which then can become overwhelming. Experts refer to this condition as post-traumatic stress disorder (PTSD). In this disorder, it is not possible, or only with difficulty, for affected individuals to unlearn the once-learned connection between a neutral environmental stimulus and the learned fear response, which impairs the success of therapies.

Knowing that the neurotransmitter serotonin plays an important role in the development of fear, the research team explored its role in extinction learning, i.e. the unlearning of fear, in greater detail. To this end, they examined so-called knock-out mice that lack a certain serotonin receptor -- the 5-HT2C receptor -- due to genetic modifications. These mice learned in one day to associate a certain sound with a mild but unpleasant electrical stimulus. "As a result of this learning process, on the following day they showed a fear response that was characterized by a motionless pause as soon as the tone was played, which we refer to as 'freezing'," explains Katharina Spoida.

Absence of the receptor is an advantage

In the next step, the researchers repeatedly played the tone to the mice without applying the electrical stimulus. "Interestingly, we noticed that knock-out mice learned much faster that the tone does not predict the fear stimulus than mice who lacked this specific genetic modification," says Katharina Spoida. "Consequently, it looks like the absence of the serotonin receptor provides an advantage for extinction learning."

The researchers investigated this phenomenon in more detail and found that the knock-out mice showed changes in their neuronal activity in two different brain areas. One of these is a specific sub-region of the dorsal raphe nucleus (DRN), which is typically the main site of serotonin production in our brains. In addition, the researchers discovered aberrant neuronal activity in the so-called bed nucleus of the stria terminalis (BNST), which is a part of the so called extended amygdala. "In the knock-out mice, we first found an increased basal activity in certain serotonin-producing cells of the dorsal raphe nucleus. In a subsequent step, we showed that the absence of the receptor also alters neuronal activity in two subnuclei of the BNST, which ultimately supports extinction learning," describes first author Sandra Süß. The research results also indicate a connection between the two brain regions, which leads the scientists to assume that an interplay is significant for improved extinction learning.

Possible effect of medication revealed

The results of the study may reveal how drugs typically used in the treatment of PTSD affect the brain regions analysed in this study. "There are already drugs in clinical use that regulate the amount of available serotonin, so-called selective serotonin reuptake inhibitors, or SSRIs for short," points out Katharina Spoida.

"Taking these drugs over a prolonged period of time causes the relevant receptor to become less responsive to serotonin, similar to our knock-out model. Therefore, we assume that the changes we've described could be essential for the positive effect of SSRIs," adds Sandra Süß. The researchers hope that their findings will help to develop more targeted treatment strategies for PTSD patients in the future.

https://www.sciencedaily.com/releases/2022/12/221205104218.htm

Studies ID ways to help young adults avoid health impacts of stress

December 5, 2022

Science Daily/North Carolina State University

It's well established that experiencing stress can hurt our physical health. Now two new studies find that younger adults who take preemptive steps to respond to stress are better able to avoid those negative health outcomes.

"The fact that we have two studies with the same results highlights the importance of proactive coping for younger adults when it comes to handling stress," says Shevaun Neupert, corresponding author of a paper on the two studies and a professor of psychology at North Carolina State University.

"These results are important for helping us work with people to build resilience, since proactive coping refers to skills that can be taught. The findings also suggest that younger adults, in particular, can benefit significantly from these skills."

Proactive coping is an umbrella term for behaviors that allow people to avoid future stressors or prepare themselves to respond to those stressors. These can be behavioral, such as saving money to deal with unexpected expenses, or cognitive, such as visualizing how to deal with potential challenges.

"You can also think of proactive coping as a way of helping people continue to work toward their goals, even when dealing with challenges," Neupert says.

The first of the two studies focused on skills that allowed people to concentrate on their goals when dealing with stressors. For this study, the researchers enlisted 223 people: 107 younger adults (ages 18-36) and 116 older adults (ages 60-90). Study participants completed an initial survey that focused on understanding goal-oriented proactive coping behaviors that the participants engaged in. The participants then completed daily surveys for the next eight days, recording the stressors they experienced each day, as well as their physical health symptoms.

"We found that younger adults who consistently engaged in proactive coping, such as thinking about what they need in order to be successful, experienced fewer negative physical health symptoms on stressful days," Neupert says. "However, there was no positive or negative effect of proactive coping for older adults."

The second study focused on efforts aimed at avoiding or preventing stressors. For this study, the researchers enlisted 140 people between the ages of 19 and 86. Study participants completed a baseline survey designed to capture their stress-prevention proactive coping behaviors. After that, the study participants completed daily surveys for 29 consecutive days, reporting on their daily stressors and physical health.

For this study, the researchers found that adults between the ages of 19 and 36 who engaged in proactive coping reported little or no drop-off in physical health on stressful days, compared to adults in the same age range who engage in less proactive coping. However, as with the first study, proactive coping had no effect for older adults.

"The effects in the both studies were linear, so the more proactive coping younger adults engaged in, the better their physical health on stressful days," Neupert says.

"These findings suggest there is tremendous value in teaching young people how to engage in proactive coping, starting with college-age young adults, but extending through to people who are established in adulthood."

https://www.sciencedaily.com/releases/2022/12/221205104145.htm

Playing the piano boosts brain processing power and helps lift the blues

December 2, 2022

Science Daily/University of Bath

A new study published by researchers at the University of Bath demonstrates the positive impact learning to play a musical instrument has on the brain's ability to process sights and sounds, and shows how it can also help to lift a blue mood.

Publishing their findings in the academic journal Nature Scientific Reports, the team behind the study shows how beginners who undertook piano lessons for just one hour a week over 11 weeks reported significant improvements in recognising audio-visual changes in the environment and reported less depression, stress and anxiety.

In the randomised control study, 31 adults were assigned into either a music training, music listening, or a control group. Individuals with no prior musical experiences or training were instructed to complete weekly one-hour sessions. Whilst the intervention groups played music, the control groups either listened to music or used the time to complete homework.

The researchers found that within just a few weeks of starting lessons*, people's ability to process multisensory information -- i.e., sight and sound -- was enhanced. Improved 'multisensory process' has benefits for almost every activity we participate in -- from driving a car and crossing a road, to finding someone in a crowd or watching TV.

These multisensory improvements extended beyond musical abilities. With musical training, people's audio-visual processing became more accurate across other tasks. Those who received piano lessons showed greater accuracy in tests where participants were asked to determine whether sound and vision 'events' occurred at the same time.

This was true both for simple displays presenting flashes and beeps, and for more complex displays showing a person talking. Such fine-tuning of individuals' cognitive abilities was not present for the music listening group (where participants listened to the same music as played by the music group), or for the non-music group (where members studied or read).

In addition, the findings went beyond improvements in cognitive abilities, showing that participants also had reduced depression, anxiety and stress scores after the training compared to before it. The authors suggest that music training could be beneficial for people with mental health difficulties, and further research is currently underway to test this.

Cognitive psychologist and music specialist Dr Karin Petrini from the University of Bath's Department of Psychology, explained: "We know that playing and listening to music often brings joy to our lives, but with this study we were interested in learning more about the direct effects a short period of music learning can have on our cognitive abilities.

"Learning to play an instrument like the piano is a complex task: it requires a musician to read a score, generate movements and monitor the auditory and tactile feedback to adjust their further actions. In scientific terms, the process couples visual with auditory cues and results in a multisensory training for individuals.

"The findings from our study suggest that this has a significant, positive impact on how the brain processes audio-visual information even in adulthood when brain plasticity is reduced."

Notes

·       Each music training session included two segments. The first 20-minute segment was dedicated to finger exercise. The second segment consisted of learning songs from the ABRSM 2017-2018 piano grade one exam list for 40 minutes. All training sessions were carried out on a one-to-one basis. Participants learned these pieces in the order presented below. They proceeded to the next song once they could play the former one correctly and fluently:

·       William Gillock A Stately Sarabande. Classic Piano Repertoire (Elementary).

·       Johann Christian Bach Aria in F, BWV Anh. II 131.

·       Giuseppe Verdi La donna è mobile (from Rigoletto).

·       Bryan Kelly Gypsy Song: No. 6 from A Baker's Dozen.

·       Traditional American Folk Song: When the saints go marching in.

https://www.sciencedaily.com/releases/2022/12/221202124841.htm

Pregnant moms' stress may accelerate cell aging of white, not Black, kids

December 2, 2022

Science Daily/University of California - San Francisco

Does stress during pregnancy impact children's cell aging, and does race matter? The answer is yes, according to a new UC San Francisco study published Dec. 2 in Psychological Medicine.

UCSF researchers followed 110 white and 112 Black women from age 10 to about 40 as well as their first child (average age 8) to understand stress influences on the women's health and its effects on their children.

What they found surprised them. Financial stress during pregnancy, such as job loss and the inability to pay bills, was linked to accelerated cellular aging of white children but not Black children.

"Ours is the first study we know of that examined effects of stressor type and timing on this aspect of health for white and Black mothers and their children," said lead study author Stefanie Mayer, PhD, UCSF assistant professor of psychiatry at the Weill Institute for Neurosciences. "We can speculate on the reasons for the results, but the truth is we need to do more research to understand them."

Cellular age can be measured by the length of one's telomeres, the protective DNA caps at the end of chromosomes. Telomere length naturally shortens with age, and shorter telomeres predict earlier onset of illnesses such as heart disease and diabetes as well as earlier death.

Previous studies showed that prenatal stressors are linked to shorter offspring telomeres, but those studies comprised mostly white mothers. The UCSF study recruited an equal number of white and Black mothers, and examined how stressors that occurred during their adolescence (pre-pregnancy), pregnancy and throughout their lifespan affected their children's telomeres.

No Effect Seen Outside Prenatal Period

The telomere effect in white children was seen only for stressors during pregnancy -- not adolescence or across the lifespan. Non-financial stressors, such as divorce or death of a loved one, had no observable telomere effect on children of either race.

While the reason for the difference in prenatal results by race is unknown, researchers offered several possibilities. One is that coping strategies developed by Black women may reduce the impact of maternal stress.

"We must continue to study and understand how stress -- and resilience to stress -- is transmitted in Black mothers, as well as in other understudied racial-ethnic communities," Mayer said. "Understanding how racial disparities in health originate and transmit across generations is a critical public health issue."

Prenatal Support is Key

More research is also needed to understand definitively whether and how pregnancy stress affects Black children's telomeres, as the stress measures used in this study may not have captured the unique stressors of Black women, such as discrimination and institutionalized racism, noted Elissa Epel, PhD, the study's senior author and UCSF professor of psychiatry at Weill Institute for Neurosciences.

"Given racial health disparities and the role of stress in other important pregnancy health outcomes, such as birth weight and preterm birth, it is critical to support all women during this important period," said Epel. "We must work harder to identify women with high levels of toxic stress and social adversity to provide interventions that address not just feelings of stress and depression but issues such as food insecurity, financial strain and housing instability."

Mindfulness interventions can reduce stress and depression during pregnancy and for years after, UCSF researchers reported this week in a separate study.

https://www.sciencedaily.com/releases/2022/12/221202124830.htm

Small studies of 40Hz sensory stimulation confirm safety, suggest Alzheimer's benefits

December 1, 2022

Science Daily/Picower Institute at MIT

Researchers report early stage clinical study results of tests with non-invasive 40Hz light and sound treatment.

A pair of early stage clinical studies testing the safety and efficacy of 40Hz sensory stimulation to treat Alzheimer's disease has found that the potential therapy was well tolerated, produced no serious adverse effects and was associated with some significant neurological and behavioral benefits among a small cohort of participants.

"In these clinical studies we were pleased to see that volunteers did not experience any safety issues and used our experimental light and sound devices in their homes consistently," said Li-Huei Tsai, Picower Professor in the The Picower Institute for Learning and Memory at MIT and senior author of the paper describing the studies in PLOS ONE Dec. 1. "While we are also encouraged to see some significant positive effects on the brain and behavior, we are interpreting them cautiously given our study's small sample size and brief duration. These results are not sufficient evidence of efficacy, but we believe they clearly support proceeding with more extensive study of 40Hz sensory stimulation as a potential non-invasive therapeutic for Alzheimer's disease."

In three studies spanning 2016-2019, Tsai's lab discovered that exposing mice to light flickering or sound clicking at the gamma-band brain rhythm frequency of 40Hz -- or employing the light and sound together -- produced widespread beneficial effects. Treated mice modeling Alzheimer's disease pathology experienced improvements in learning and memory; reduced brain atrophy, neuron and synapse loss; and showed lower levels of the hallmark Alzheimer's proteins amyloid beta and phosphorylated tau compared to untreated controls. The stimulation appears to produce these effects by increasing the power and synchrony of the 40Hz brain rhythm, which the lab has shown profoundly affects the activity of several types of brain cells, including the brain's vasculature.

Study designs

Based on those encouraging results, Diane Chan, a neurologist at Massachusetts General Hospital and a postdoctoral clinical fellow in Tsai's lab, led the two new clinical studies at MIT. One set of tests, a "Phase 1" study, enrolled 43 volunteers of various ages including 16 people with early stage Alzheimer's to confirm that exposure to 40Hz light and sound was safe and test whether it increased 40Hz rhythm and synchrony after a few minutes of exposure, as measured with EEG electrodes. The study also included two patients with epilepsy at the University of Iowa who consented to having measurements taken in deeper brain structures during exposure to 40Hz sensory stimulation while undergoing epilepsy-related surgery.

The second set of tests, a "Phase 2A" pilot study, enrolled 15 people with early stage Alzheimer's disease in a single-blinded, randomized, controlled study to receive exposure to 40Hz light and sound (or non-40Hz "sham" stimulation for experimental controls) for an hour a day for at least three months. They underwent baseline and follow-up visits including EEG measurements during stimulation, MRI scans of brain volume, and cognitive testing. The stimulation device the volunteers used in their homes (a light panel synchronized with a speaker) was equipped with video cameras to monitor device usage. Participants also wore sleep-monitoring bracelets during their participation in the trial.

The Phase 2A trial launched just before the onset of the Covid-19 pandemic in 2020, causing some participants to become unable to undergo follow ups after three months. The study therefore only reports results through a four-month period.

Study results

In the Phase 1 study volunteers filled out a questionnaire on side effects, reporting a few minor but no major adverse effects. The most common was feeling "sleepy or drowsy." Meanwhile, measurements taken with EEG scalp electrodes clustered at frontal and occipital sites showed significant increases in 40Hz rhythm power at each cortical site among cognitively normal younger and older participants as well as volunteers with mild Alzheimer's. The readings also demonstrated significant increase in coherence at the 40Hz frequency between the two sites. Between the two volunteers with epilepsy, measurements showed significant increases in 40Hz power in deeper brain regions such as the gyrus rectus, amygdala, hippocampus and insula with no adverse events including seizures.

In the Phase 2A study, neither treated nor control volunteers reported serious adverse events. Both groups used their devices 90 percent of the time. The eight volunteers treated with 40Hz stimulation experienced several beneficial effects that reached statistical significance compared to the seven volunteers in the control condition. Control participants exhibited two signs of brain atrophy as expected with disease progression: reduced volume of the hippocampus and increased volume of open spaces, or ventricles. Treated patients did not experience significant changes in these measures. Treated patients also exhibited better connectivity across brain regions involved in the brain's default mode and medial visual networks, which are related to cognition and visual processing respectively. Treated patients also exhibited more consistent sleep patterns than controls.

Neither the treatment and control groups showed any differences after just three months on most cognitive tests, but the treatment group did perform significantly better on a face-name association test, a memory task with a strong visual component. The two groups, which were evenly matched by age, gender, APOE risk gene status, and cognitive scores, differed by years of education but that difference had no relationship to the results, the researchers wrote.

"After such a short time we didn't expect to see significant effects on cognitive measures so it was encouraging to see that at least on face-name association the treatment group did perform significantly better," Chan said.

In PLOS ONE the researchers concluded: "Overall, these findings suggest that 40Hz GENUS has positive effects on AD-related pathology and symptoms and should be studied more extensively to evaluate its potential as a disease-modifying intervention for AD."

After the study ended all participants were permitted to continue using the devices set to provide the 40Hz stimulation.

The MIT team is now planning new clinical studies to test whether 40Hz sensory stimulation may be effective in preventing the onset of Alzheimer's in high-risk volunteers and is launching preliminary studies to determine its therapeutic potential for Parkinson's disease and Down syndrome. Cognito Therapeutics, an MIT spin-off company co-founded by Tsai and co-author Ed Boyden, Y. Eva Tan Professor of Neurotechnology at MIT, has launched Phase 3 trials of 40Hz sensory stimulation as an Alzheimer's treatment using a different device.

Tsai, Boyden and co-author Emery N. Brown, Edward Hood Taplin Professor of Computational Neuroscience and Medical Engineering at MIT, are among the co-founders of MIT's Aging Brain Initiative, which has advanced this collaboration and other neurodegeneration research at MIT.

In addition to Tsai, Chan, Boyden and Brown, the study's other authors are Ho-Jun Suk, Brennan Jackson, Noah Milman, Danielle Stark, Elizabeth Klerman, Erin Kitchener, Vanesa S. Fernandez Avalos, Gabrielle de Weck, Arit Banerjee, Sara D. Beach, Joel Blanchard, Colton Stearns, Aaron D. Boes, Brandt Uitermarkt, Phillip Gander, Matthew Howard III, Eliezer J. Sternberg, Alfonso Nieto-Castanon, Sheeba Anteraper, Susan Whitfield-Gabrieli, and Bradford C. Dickerson.

Funding for the study came from sources including the Robert A. and Renee E. Belfer Family Foundation, Ludwig Family Foundation, JPB Foundation, Eleanor Schwartz Charitable Foundation, the Degroof-VM Foundation, Halis Family Foundation, and David B Emmes, Gary Hua and Li Chen, the Ko Han Family, Lester Gimpelson, Elizabeth K. and Russell L. Siegelman, Joseph P. DiSabato and Nancy E. Sakamoto, Alan and Susan Patricof, Jay L. and Carroll D Miller, Donald A. and Glenda G. Mattes, the Marc Haas Foundation, Alan Alda, and Dave Wargo.

https://www.sciencedaily.com/releases/2022/12/221201163449.htm

Peek of how ketamine acts as 'switch' in the brain

December 1, 2022

Science Daily/University of Pennsylvania School of Medicine

Ketamine, an established anesthetic and increasingly popular antidepressant, dramatically reorganizes activity in the brain, as if a switch had been flipped on its active circuits, according to a new study by Penn Medicine researchers. In a Nature Neuroscience paper released this month, the team described starkly changed neuronal activity patterns in the cerebral cortex of animal models after ketamine administration -- observing normally active neurons that were silenced and another set that were normally quiet suddenly springing to action. This ketamine-induced activity switch in key brain regions tied to depression may impact our understanding of ketamine's treatment effects and future research in the field of neuropsychiatry.

"Our surprising results reveal two distinct populations of cortical neurons, one engaged in normal awake brain function, the other linked to the ketamine-induced brain state," said the co-lead and co-senior author Joseph Cichon, MD, PhD, an assistant professor of Anesthesiology and Critical Care and Neuroscience in the Perelman School of Medicine at the University of Pennsylvania. "It's possible that this new network induced by ketamine enables dreams, hypnosis, or some type of unconscious state. And if that is determined to be true, this could also signal that it is the place where ketamine's therapeutic effects take place."

Anesthesiologists routinely deliver anesthetic drugs before surgeries to reversibly alter activity in the brain so that it enters its unconscious state. Since its synthesis in the 1960s, ketamine has been a mainstay in anesthesia practice because of its reliable physiological effects and safety profile. One of ketamine's signature characteristics is that it maintains some activity states across the surface of the brain (the cortex). This contrasts with most anesthetics, which work by totally suppressing brain activity. It is these preserved neuronal activities that are thought to be important for ketamine's antidepressant effects in key brain areas related to depression. But, to date, how ketamine exerts these clinical effects remains mysterious.

In their new study, the researchers analyzed mouse behaviors before and after they were administered ketamine, comparing them to control mice who received placebo saline. One key observation was that those given ketamine, within minutes of injection, exhibited behavioral changes consistent with what is seen in humans on the drug, including reduced mobility, impaired responses to sensory stimuli, which are collectively termed "dissociation."

"We were hoping to pinpoint exactly what parts of the brain circuit ketamine affects when it's administered so that we might open the door to better study of it and, down the road, more beneficial therapeutic use of it," said co-lead and co-senior author Alex Proekt, MD, PhD, an associate professor of Anesthesiology and Critical Care at Penn.

Two-photon microscopy was used to image cortical brain tissue before and after ketamine treatment. By following individual neurons and their activity, they found that ketamine turned on silent cells and turned off previously active neurons.

The neuronal activity observed was traced to ketamine's ability to block the activity of synaptic receptors -- the junction between neurons -- called NMDA receptors and ion channels called HCN channels. The researchers found that they could recreate ketamine's effects without the medications by simply inhibiting these specific receptors and channels in the cortex. The scientists showed that ketamine weakens several sets of inhibitory cortical neurons that normally suppress other neurons. This allowed the normally quiet neurons, the ones usually being suppressed when ketamine wasn't present, to become active.

The study showed that this dropout in inhibition was necessary for the activity switch in excitatory neurons -- the neurons forming communication highways, and the main target of commonly prescribed antidepressant medications. More work will need to be undertaken to determine whether the ketamine-driven effects in excitatory and inhibitory neurons are the ones behind ketamine's rapid antidepressant effects.

"While our study directly pertains to basic neuroscience, it does point at the greater potential of ketamine as a quick-acting antidepressant, among other applications," said co-author Max Kelz, MD, PhD,a distinguished professor of Anesthesiology and vice chair of research in Anesthesiology and Critical Care. "Further research is needed to fully explore this, but the neuronal switch we found also underlies dissociated, hallucinatory states caused by some psychiatric illnesses."

Support for the study was provided by the Foundation for Anesthesia Education and Research, and the National Institutes of Health (T32NS091006, R01GM124023-01A1, R01GM088156-08, R01 EY020765).

https://www.sciencedaily.com/releases/2022/12/221201141927.htm

Prenatal wellness classes cut moms' depression in half up to eight years later

November 30, 2022

Science Daily/University of California - San Francisco

A low-cost, prenatal intervention benefits mothers' mental health up to eight years later, a new UC San Francisco study finds.

In the study, one of the first to look at outcomes so far into the future, pregnant women who participated in a group wellness class that met weekly for eight weeks were half as likely to be depressed eight years later compared to women who received standard care, according to the study published in the Journal of Consulting and Clinical Psychology.

Previous research on the same group of women found the intervention also cut their short-term risk of depression and diabetes, and supported healthier stress responses in their children.

"Given the economic and social burden of maternal depression and its potential impact on offspring, our findings suggest a meaningful benefit of a modest investment during pregnancy that supports well-being across two generations," said Danielle Roubinov, PhD, UCSF assistant professor of psychiatry and first author of the study.

The eight-week class intervention, led by Elissa Epel, PhD, UCSF professor of psychiatry and her team, involved groups of eight to 10 pregnant women who met for two hours a week to practice mindfulness-based stress reduction exercises, focusing especially on mindful eating, breathing and movement. They were led through group lessons and activities by a master's degree-level health professional. The women also received two phone sessions and a postpartum "booster" group session with their infants.

BIPOC Study Participants Were Priority

Historically, most studies on prenatal depression have comprised primarily white women -- but not this one, noted Nicki Bush, PhD, professor of pediatrics and psychiatry at the UCSF Weill Institute for Neurosciences and senior author on the study.

"Our participants were lower-income, racially and ethnically diverse women who are systemically exposed to factors that put them at risk for depression, such as racism and economic hardship," Bush said. "Also, the final years of the study were during the COVID-19 pandemic, when depression rates were higher for everyone, and the burden placed on communities of color was even greater. Even so, the treatment effects held up."

In the study, 162 women were assigned to either the intervention group or standard care group. The women's depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9) before the wellness intervention classes, after the wellness classes, and 1, 2, 3-4, 5, 6 and 8 years later.

Though both groups of women had equal symptoms of depression before the class, 12 percent of the women who were part of the wellness class reported moderate or severe depressive symptoms at the eight-year mark compared to 25 percent of the women who received standard care, which was a consistent pattern throughout the years.

"Mindfulness practice is known to help alleviate stress in many situations and can meaningfully affect coping and health, and it seems here that it was particularly powerful during pregnancy, with enduring effects," Bush said. "Our sense is that the community connections and social support involved with the (wellness class) group were therapeutic as well."

Stress Management, Nutrition and Exercise During Pregnancy

The researchers are currently collecting additional data to better understand how the intervention had such a long-term effect. Potential mechanisms include long-term changes in coping and stress reactivity, nutrition, and exercise.

Up to 27 percent of pregnant women suffer prenatal depression, which is predictive of postnatal depression. Maternal depression is also associated with social, emotional and cognitive deficits in offspring.

"This dramatic demonstration of both short-term reduction of depressive symptoms and long-term prevention of more severe maternal depression, even during the pandemic, is remarkable, even to us researchers," Epel said. "It's likely that the effects of increased stress resilience in these women is having pervasive effects on their own health and their children. We would never have known about the durability of these changes if Dr. Bush and her team had not followed them for eight years. We already know pregnancy is a critical period and the lesson here is that we need to heavily invest in pregnancy wellness interventions."

The researchers hope the low cost and relatively short time commitment of the intervention class will make it easy to scale up to larger groups of pregnant women -- especially women of color and those with lower incomes.

"It's critical to have interventions that meet the needs of lower-income, Black, Indigenous, and people of color, who are especially likely to experience the stress of social inequities," said Roubinov. "We're excited to see how these results can be scaled to reach more women, and a more diverse pool of women."

https://www.sciencedaily.com/releases/2022/11/221130151542.htm

Fear of professional backlash may keep women from speaking up at academic conferences

November 30, 2022

Science Daily/Association for Psychological Science

Academic conferences provide invaluable opportunities for researchers to present their work and receive feedback from attendees during question-and-answer sessions. Women are less likely to ask questions during these sessions, however, and research in Psychological Science suggests that this may be due to anxiety about how colleagues will receive their comments.

Addressing these concerns could help women academics contribute more proportionally to the scientific process, said lead author Shoshana N. Jarvis (University of California, Berkeley), who conducted the research with Charles R. Ebersole (American Institutes for Research), Christine Q. Nguyen, Minwan Zhu, and Laura J. Kray (University of California, Berkeley).

"More men participate in Q&A sessions compared to what we would expect based on who's in the audience. When asked, men say they are more comfortable participating, and women are more afraid of experiencing backlash for their participation," Jarvis said in an interview.

In the first of two studies, Jarvis and colleagues observed recordings of 193 Q&A interactions that occurred following 32 research talks at a single-track interdisciplinary conference. Approximately 63% of the conference's 375 attendees identified as men and 35% identified as women, according to attendees' conference registrations, survey responses, pronoun listings on personal websites, appearances, and names. The remaining 2% of attendees were excluded from the analysis because they identified as nonbinary or the researchers could not determine their gender.

In line with previous research on how gender influences conference participation, 78% of Q&A interactions were found to be initiated by men stepping up to the microphone, whereas women did so just 22% of the time. Men were also more likely than women to be one of the first four audience members to participate in a Q&A session.

Gender was not found to significantly influence attendees' behavior when they did ask questions, however. Research assistants who were unaware of what Jarvis and colleagues were studying rated men and women attendees as equally likely to challenge other researchers by questioning their expertise or the quality of their work. Men and women were also rated as equally likely to perform polite behaviors such as thanking a speaker for sharing their research or complimenting their work. Additionally, attendees were 24% more likely to be rated as polite when the speaker they were addressing was a woman, regardless of their own gender.

"When people are in power, they use that power to display dominant behaviors and disproportionately occupy space," as has historically been the case with men in academia, Jarvis and colleagues wrote. "Men's dominance in Q&A sessions seems to be driven by their greater willingness to jump into the discussion rather than in how they communicate while at the microphone."

In the second study, Jarvis and colleagues surveyed researchers by email 6 months after they attended a psychology conference in the United States. The surveys were completed by 234 conference attendees, of whom 69% were women and 28% were men. The remaining 3% of respondents were excluded from the analysis because they were nonbinary or did not disclose their gender on the survey.

The survey results showed that women respondents reported being less comfortable participating in Q&A sessions and more likely to fear experiencing professional backlash if they did participate. Women and men were equally likely to report holding back questions, but they gave different reasons for doing so: Women were more likely to hold back because of anxiety, but men did so to allow other people time to ask questions.

"While we expected men to ask more questions than women, we were surprised to learn that men report holding back questions to make space for other people. Despite this level of self-awareness, it does not seem to be enough to mitigate the collective gender differences," Jarvis said.

Future work could extend these findings by exploring how race and other identities may influence conference attendees' willingness to participate in Q&A sessions, as well as what changes could help mitigate gender differences in participation, Jarvis and colleagues concluded.

"By understanding the psychological barriers impacting women's participation in Q&A sessions, we set the stage to begin work toward structural changes that would create a more equitable space for scientific discourse," the researchers wrote.

https://www.sciencedaily.com/releases/2022/11/221130151540.htm

Experiences of daily stress decrease as people age

November 30, 2022

Science Daily/Penn State

Stories about how daily stress can negatively impact people's lives, from physical health to mental and emotional well-being, are frequently in the media. But there is good news about the experience of daily stress as people age. Results from a recent research study led by David Almeida, professor of human development and family studies at Penn State, showed that the number of daily stressors and people's reactivity to daily stressors decreases with age. The findings were published in the journal Developmental Psychology.

"There's something about growing old that leads to fewer stressors," said Almeida. "This could be the types of social roles that we fill as we age. As younger people, we may be juggling more, including jobs, families and homes, all of which create instances of daily stress. But as we age, our social roles and motivations change. Older people talk about wanting to maximize and enjoy the time they have."

The research team utilized data from the National Study of Daily Experiences (NSDE), a national study led by Almeida at Penn State that has collected comprehensive data on daily life from over 40,000 days in the lives of more than 3,000 adults across a 20-year time span, starting in 1995. Respondents were aged 25 to 74 when the study began and were invited to participate in the NSDE from the larger Midlife in the United States (MIDUS) project led by the University of Wisconsin-Madison Institute on Aging.

Respondents participated in telephone interviews that assessed daily levels of stress for eight consecutive days. These daily assessments were repeated at approximately nine-year intervals, providing a longitudinal daily diary across 20 years.

The researchers noted a decrease in the effects of daily stress both in the number of daily stressors that people reported, as well as their emotional reactivity to them. For example, 25-year-olds reported stressors on nearly 50% of days, while 70-year-olds reported stressors on only 30% of days.

In addition to the decrease in the number of daily stressors reported, Almeida and the research team also found that as people age, they are less emotionally reactive to daily stressors when they do happen.

"A 25-year-old is much grumpier on the days when they experience a stressor, but as we age, we really figure out how to decrease those exposures," said Almeida, who noted that daily stress steadily decreases until mid-50s, when people are the least affected by stress exposures.

While these findings show a decrease in reports of, and reactivity to, daily stressors into the mid-50s, Almeida notes that early indicators show that older age, into the late 60s and early 70s, may bring more challenges and a slight increase in instances of daily stress.

With this finding, Almeida is looking forward to the next round of data collection for MIDUS, which will be the first since the COVID-19 pandemic began in early 2020. This new round of data collection will allow Almeida and his team to assess the impact of the pandemic on daily stress reactivity.

The next round of data collection also will allow the team to further study how people grow and change during adulthood.

"Growing older from 35 to 65 is very different than growing older from 65 to 95," said Almeida. "We've started to see that in the data already, but this next round of data collection and analysis will give us an even greater understanding of what that looks like."

"At the end of the next post-pandemic data collection in a couple of years, I'll be in my early 60s, and when I started this project, I was in my late 20s," he continued. "My own development has occurred during this study of midlife, and it has been enlightening to watch these findings play out in my own life."

According to Almeida, we are all aging and growing older in various ways. How we age is depending on not only the challenges we face, but how we handle those challenges.

"A lot of my prior work looked at these small, daily stressors -- being late to a meeting, having an argument with a partner, caring for a sick child -- and found that our emotional responses to these events are predictive of later health and well-being, including chronic conditions, mental health and even mortality. With this new research, it's encouraging to see that as we age, we begin to deal with these stressors better. On average, the experience of daily stress won't get worse, but in fact get better."

https://www.sciencedaily.com/releases/2022/11/221130151532.htm

Excessive television viewing in childhood is a risk factor for later smoking and gambling disorders

November 30, 2022

Science Daily/University of Otago

Excessive television viewing as a child can lead to a higher risk of tobacco use and gambling disorders in adulthood, a new University of Otago study shows.

The researchers used unique, follow-up data from the Dunedin Multidisciplinary Health and Development Study (known as the Dunedin Study) to investigate how television viewing in childhood was related to the risk of having a substance use disorder or disordered gambling in adulthood.

Study author Dr Helena McAnally says that the study indicates that excessive leisure time television viewing between the age of 5 and 15, may be a risk factor for the development of later disorders.

"People often talk of television viewing as an addiction; this research indicates that, for some people, television viewing may be an early expression of an addictive disorder or may lead to later substance-related and other addictive disorders," she says.

Spending time watching television during childhood and adolescence was associated with a higher risk of alcohol, tobacco, cannabis disorders and disordered gambling in adulthood. For tobacco and gambling, these associations were independent of other potential influences on these outcomes such as sex, socioeconomic status, and measures of childhood self-control.

Co-author Professor Bob Hancox says excessive leisure time television viewing in childhood and adolescence has been associated with a range of poorer adult health and wellbeing outcomes, but "to our knowledge this research is among the first to assess how a common, but potentially addictive behaviour, such as television viewing is related to later substance disorder and disordered gambling."

The study highlights the potential need for guidance on digital health and wellbeing, he says.

"Public health agencies have put great effort into advocating for safer alcohol use and safe sexual practices; similar campaigns could be used to advocate for safe screen use.

"The American Academy of Pediatrics' previous recommendation of a daily average limit of two hours of screen time may remain a reasonable guide for leisure-time screen time in children and adolescents," Professor Hancox says.

https://www.sciencedaily.com/releases/2022/11/221129184438.htm