Deep sleep takes out the trash

January 20, 2021

Science Daily/Northwestern University

A new Northwestern University study reaffirms the importance of getting a good night's sleep.

By examining fruit flies' brain activity and behavior, the researchers found that deep sleep has an ancient, restorative power to clear waste from the brain. This waste potentially includes toxic proteins that may lead to neurodegenerative disease.

"Waste clearance could be important, in general, for maintaining brain health or for preventing neurogenerative disease," said Dr. Ravi Allada, senior author of the study. "Waste clearance may occur during wake and sleep but is substantially enhanced during deep sleep."

The study will publish tomorrow (Jan. 20) in the journal Science Advances.

Allada is the Edward C. Stuntz Distinguished Professor in Neuroscience and chair of the Department of Neurobiology in the Northwestern's Weinberg College of Arts and Sciences. He also is associate director of Northwestern's Center for Sleep and Circadian Biology. Bart van Alphen, a postdoctoral fellow in Allada's laboratory, was the paper's first author.

Although fruit flies seem very different from humans, the neurons that govern flies' sleep-wake cycles are strikingly similar to our own. For this reason, fruit flies have become a well-studied model organism for sleep, circadian rhythms and neurodegenerative diseases.

In the current study, Allada and his team examined proboscis extension sleep (PES), a deep-sleep stage in fruit flies, which is similar to deep, slow-wave sleep in humans. The researchers discovered that, during this stage, fruit flies repeatedly extend and retract their proboscis (or snout).

"This pumping motion moves fluids possibly to the fly version of the kidneys," Allada said. "Our study shows that this facilitates waste clearance and aids in injury recovery."

When Allada's team impaired flies' deep sleep, the flies were less able to clear an injected non-metabolizable dye from their systems and were more susceptible to traumatic injuries.

Allada said this study brings us closer to understanding the mystery of why all organisms need sleep. All animals -- especially those in the wild -- are incredibly vulnerable when they sleep. But research increasingly shows that the benefits of sleep -- including crucial waste removal -- outweigh this increased vulnerability.

"Our finding that deep sleep serves a role in waste clearance in the fruit fly indicates that waste clearance is an evolutionary conserved core function of sleep," the paper's coauthors write. "This suggests that waste clearance may have been a function of sleep in the common ancestor of flies and humans."

https://www.sciencedaily.com/releases/2021/01/210120151044.htm

Fragmented sleep patterns can predict vulnerability to chronic stress

January 13, 2021

Science Daily/New York University

New research from NYU Abu Dhabi's Laboratory of Neural Systems and Behavior for the first time used an animal model to demonstrate how abnormal sleep architecture can be a predictor of stress vulnerability. These important findings have the potential to inform the development of sleep tests that can help identify who may be susceptible -- or resilient -- to future stress.

In the study, Abnormal Sleep Signals Vulnerability to Chronic Social Defeat Stress, which appears in the journal Frontiers in Neuroscience, NYUAD Assistant Professor of Biology Dipesh Chaudhury and Research Associate Basma Radwan describe their development of a mouse model to detect how disruptions in Non-rapid Eye Movement (NREM) sleep result in increased vulnerability to future stress.

The researchers assessed the sleep characteristics of both stress-susceptible and stress-resilient mice before and after experiencing chronic social defeat (CSD) stress. The social behavior of the mice post-stress was classified in two main phenotypes: those susceptible to stress that displayed social avoidance and those that were resilient to stress. Pre-CSD, mice susceptible to stress displayed increased fragmentation of Non-Rapid Eye Movement (NREM) sleep due to increased switching between NREM and wake and shorter average duration of NREM bouts, relative to mice resilient to stress. Their analysis showed that the pre-CSD sleep features from both phenotypes of mice allowed prediction of susceptibility to stress with more than 80 percent accuracy. Post-CSD, susceptible mice maintained high NREM fragmentation during the light and dark phase while resilient mice exhibited high NREM fragmentation only in the dark.

The findings demonstrate that mice that become susceptible to CSD stress exhibit pre-existing abnormal sleep/wake characteristics prior to stress exposure. In addition, subsequent exposure to stress further impairs sleep and the homeostatic response.

"Our study is the first to provide an animal model to investigate the relationship between poor sleep continuity and vulnerability to chronic stress and depressive disorders," said Chaudhury and Radwan. "This marker of vulnerability to stress opens up avenues for many possible future studies that could further explain the underlying molecular processes and neural circuitry that lead to mood disorders."

https://www.sciencedaily.com/releases/2021/01/210112085407.htm

Study shows meaningful lockdown activity is more satisfying than busyness

January 11, 2021

Science Daily/RMIT University

New research shows people who pursue meaningful activities -- things they enjoy doing -- during lockdown feel more satisfied than those who simply keep themselves busy.

The study, published in PLOS ONE, shows you're better off doing what you love and adapting it to suit social distancing, like swapping your regular morning walk with friends for a zoom exercise session.

Simply increasing your level of activity by doing mindless busywork will leave you unsettled and unsatisfied.

Co-lead researcher Dr Lauren Saling from RMIT University in Melbourne, Australia said while novelty lockdown activities -- like baking or painting -- have their place, trying to continue what you enjoyed before lockdown can be more rewarding.

"Busyness might be distracting but it won't necessarily be fulfilling," she said.

"Rather, think about what activities you miss most and try and find a way of doing them."

Survey participants rated their level of wellbeing as it was during social distancing and retrospectively one month beforehand.

They also indicated how much time they spent engaged in various activities and nominated how important each activity was for them.

Although participants reported feeling more positive emotions while doing novelty 'meaningless' activities like binge watching TV, they also felt more negative emotions -- they felt unhappy just as much as they felt happy.

But when substituting activities enjoyed before lockdown -- like dining with friends -- for a virtual alternative, their positive and negative emotions were more subdued.

Saling said busyness riles you up, prompting you to change your behaviour, but meaningful activity -- doing what you enjoy -- calms you down.

"Extreme emotions are not necessarily a good thing," she said.

"Emotions are a mechanism to make you change your behaviour.

"But when you're doing what you love, it makes sense that you feel more balanced -- simply keeping busy isn't satisfying."

Saling said the study challenged assumptions that we are either happy or sad and that we can stave off sadness by keeping busy.

Rather, those who kept busy with mindless tasks felt more frustrated and even when they were happy felt less fulfilled.

"The study showed positive and negative affect worked together, not as opposites," Saling said.

"Respondents who simply stayed busy during lockdown reported an increase in both positive and negative emotions.

"This heightened emotionality will tend to shift you away from activity in general and towards meaningful activity."

The study also found the biggest change in positive emotions before and during lockdown was experienced by people aged under 40.

Saling said this was likely because it was harder for that age group to successfully substitute meaningful activities into a lockdown context.

https://www.sciencedaily.com/releases/2021/01/210111112126.htm

Heading outdoors keeps lockdown blues at bay

Study finds time spent outdoors is associated with higher levels of happiness

January 8, 2021

Science Daily/Anglia Ruskin University

A new study has found that spending time outdoors and switching off our devices is associated with higher levels of happiness during a period of COVID-19 restrictions.

Previous academic studies have indicated how being outdoors, particularly in green spaces, can improve mental health by promoting more positive body image, and lowering levels of depression and anxiety.

Jointly led by academics from Anglia Ruskin University (ARU) in the UK, the Karl Landsteiner University of Health Sciences in Austria, and Perdana University in Malaysia, this new research examined how levels of happiness during a national lockdown were affected by being outdoors, the amount of daily screen time (use of TV, computer and smartphone) and feelings of loneliness.

Using an experience sampling method (ESM), the researchers measured levels of happiness amongst a group of 286 adults three times a day, at random intervals, over a 21-day period. This allowed the participants to provide data in real-time rather than retrospectively, helping to avoid recall biases.

The research, published in the Journal of Happiness Studies, was carried out in April 2020, when the Austrian participants were allowed to leave their homes only for specific activities, which included exercise.

It found that levels of happiness were higher when participants were outdoors rather than indoors. In addition, more daily screen time and higher levels of loneliness were both associated with lower levels of happiness. The impact of loneliness on happiness was also weaker when participants were outdoors.

Co-lead author Viren Swami, Professor of Social Psychology at Anglia Ruskin University (ARU), said: "While lockdowns can help slow down the transmission of COVID-19, research has also shown that prolonged periods of lockdown take their toll on mental health.

"Our results are important in this context because they show that being able to spend time outdoors under conditions of lockdown has a beneficial impact on psychological wellbeing. Being outdoors provides opportunities to escape from the stresses of being confined at home, maintain social relationships with others, and engage in physical activity -- all of which can improve mental health.

"Our findings have practical health policy implications. Given that further lockdown restrictions have now become necessary in the UK, public health messages that promote getting some fresh air instead of staying indoors and staring at our screens could really help to lift people's mood this winter."

https://www.sciencedaily.com/releases/2021/01/210108084121.htm

Increase in pleasurable effects of alcohol over time can predict alcohol use disorder

New research challenges existing dogma that higher tolerance for stimulating and rewarding effects of alcohol leads to addiction

January 5, 2021

Science Daily/University of Chicago Medical Center

A new study out of the University of Chicago Medicine following young adult drinkers for 10 years has found that individuals who reported the highest sensitivity to alcohol's pleasurable and rewarding effects at the start of the trial were more likely to develop an alcohol use disorder (AUD) over the course of the study.

Moreover, when retested on their responses 10 years later, those who became alcoholics had the highest levels of alcohol stimulation, liking and wanting -- and these were heightened compared to their baseline with no signs of tolerance to these pleasurable effects.

The research, published on Jan. 5 in the American Journal of Psychiatry, followed a cohort of 190 young adults in a laboratory-based binge-drinking scenario at three regular intervals over the course of 10 years.

These results indicate that individuals developing an AUD are more likely to be sensitized to the effects of alcohol -- that is, they experience a stronger positive response -- rather than habituated to the substance with a lower level of response. In these same individuals, alcohol was less sedating for them from the beginning and this did not change over time.

"Prior longitudinal studies have looked at young drinkers' response to alcohol and focused primarily on the fatiguing and impairing effects of alcohol," said lead author Andrea King, PhD, professor of psychiatry and behavioral neuroscience at UChicago Medicine. "The thinking that alcoholics do not like the effects of alcohol over time is based on ad-hoc reports of patients entering treatment. Only by testing the same people over a substantial amount of time to see if alcohol responses change over time were we able to observe this elevated response to alcohol compared with placebo, and in participants who did not know the contents of the drinks, so expectancy effects were minimized."

The study showed that higher sensitivity to the euphoric and rewarding effects of alcohol can predict who will go on to have an AUD as they progress through their 20s and 30s.

"These pleasurable alcohol effects grow in intensity over time, and do not dissipate, in people progressing in excessive drinking," said King. "This tells us that having a higher sensitivity to the rewarding effects of alcohol in the brain puts such individuals at higher risk for developing addiction. It all fits a picture of persistent pleasure-seeking that increases the likelihood of habitual excessive drinking over time. Alcoholics were thought to need to drink more to finally get their desired effect when they drink, but these well-controlled data do not support that contention. They get the desirable alcohol effect early in the drinking bout and that seems to fuel wanting more alcohol."

While it may seem relatively intuitive that individuals who experience alcohol's pleasurable effects most intensely are at the greatest risk for developing drinking problems, King's findings run counter to current prominent addiction theories.

"Our results support a theory called incentive-sensitization," said King. "In response to a standard intoxicating dose of alcohol in the laboratory, ratings of wanting more alcohol increased substantially over the decade among the individuals who developed more severe AUD. Additionally, the hedonic response -- essentially, how much a person liked the effects -- remained elevated over this interval and didn't go down at all. This has traditionally been the crux of the lore of addiction -- that addicts don't like the drug (alcohol) but can't stop using it."

The participants were regular light or heavy social drinkers in their mid-20s at the start of the trial from 2004 to 2006. They were brought back for repeated testing of alcohol responses in the laboratory five and 10 years later as they approached middle adulthood. In between testing periods, participants were interviewed at near-annual intervals to track their drinking patterns and symptoms of AUD over time.

King hopes that these results can help improve our understanding of how some individuals have more vulnerability to developing AUD, while others remain social drinkers over their lifespan. She also points out that the results can help to develop better treatments for AUDs and inform earlier interventions for individuals who may be at high risk for developing an addiction.

"I'm already using this information to inform how I talk about addiction with my therapy clients," King said. "It can be frustrating for them to see other people who can have a couple drinks and just stop there. They can't understand why they repeatedly seem unable to do that, too, and I tell them, it may be because your brain responds differently to alcohol that makes it harder to stop drinking once you start. Knowing that information can empower a person to make different decisions. Even with our current pandemic, a person may drink to cope with stress or reduce negative feelings, but that doesn't mean that they don't also experience the buzz, or pleasurable effects from drinking. This is most concerning for at-risk drinkers as those responses may intensify as they progress with heavier drinking."

Based on this research, King sees the potential for a sort of "personalized medicine" approach for treating AUDs, describing how sharing an individual's "thumbprint" response to alcohol can make a difference in how they think about their consumption.

"This could be an opportunity for early intervention, comparable to how someone may get their cholesterol tested and then may be more motivated to change their diet, exercise more or start a medication to rein it in," King said. "Similarly, knowing one's acute response to alcohol and how it may indicate a person's future risk for drinking problems, one may decide to change their drinking on their own or seek help to avoid the progression to addiction."

https://www.sciencedaily.com/releases/2021/01/210105084649.htm

Difference in blood pressure between arms linked to greater early death risk

December 21, 2020

Science Daily/University of Exeter

Robust evidence from a large international study confirms that a difference in blood pressure readings between arms is linked to greater risk of heart attack, stroke and death.

Led by the University of Exeter, the global INTERPRESS-IPD Collaboration conducted a meta-analysis of all the available research, then merged data from 24 global studies to create a database of nearly 54,000 people. The data spanned adults from Europe, the US, Africa and Asia for whom blood pressure readings for both arms were available.

Funded by the National Institute for Health Research (NIHR) and published today in Hypertension, the study is the first to conclude that the greater the inter-arm blood pressure difference, the greater the patient's additional health risk.

Currently, international blood pressure guidelines advise health professionals to measure blood pressure in both arms when assessing cardiovascular risk,- yet this is widely ignored. The new study provides a new upper limit of 'normal' for an inter-arm difference in blood pressure, which is significantly lower than the current guidance. The research could lead to a change in international hypertension guidelines, meaning more at-risk patients could be identified and receive potentially life-saving treatment.

In a methodology that put patients at its heart, working with a patient advisory group at every step of the research, the team analysed data on inter-arm blood pressure difference, and tracked the number of deaths, heart attacks and strokes that occurred in the cohort over 10 years.

Lead author and GP Dr Chris Clark, of the University of Exeter Medical School, said: "Checking one arm then the other with a routinely used blood pressure monitor is cheap and can be carried out in any healthcare setting, without the need for additional or expensive equipment. Whilst international guidelines currently recommend that this is done, it only happens around half of the time at best, usually due to time constraints. Our research shows that the little extra time it takes to measure both arms could ultimately save lives."

"We've long known that a difference in blood pressure between the two arms is linked to poorer health outcomes. The large numbers involved in the INTERPRESS-IPD study help us to understand this in more detail. It tells us that the higher the difference in blood pressure between arms, the greater the cardiovascular risk, so it really is critical to measure both arms to establish which patients may be at significantly increased risk. Patients who require a blood pressure check should now expect that it's checked in both arms, at least once."

Blood pressure rises and falls in a cycle with each pulse. It is measured in units of millimetres of mercury (mmHg), and the reading is always given as two numbers: the upper (systolic) reading represents the maximum blood pressure and the lower (diastolic) value is the minimum blood pressure. A high systolic blood pressure indicates hypertension. This affects one third of the adult population and is the single leading cause globally of preventable heart attacks, strokes and deaths. A significant difference between the systolic blood pressure measurements in the two arms could be indicative of a narrowing, or a stiffening, of the arteries, which can affect blood flow. These arterial changes are recognised as a further risk marker for subsequent heart attack, stroke or early death, and should be investigated for treatment.

The researchers concluded that each mmHg difference found between the two arms, elevated predicted 10-year risk of one of the following occurring by one percent; new angina, a heart attack or stroke.

At the moment, both UK and European guidelines recognise a systolic difference of 15 mmHg or more between the two arms as the threshold indicative of additional cardiovascular risk. This new study found that a lower threshold of 10 mmHg was clearly indicative of additional risk, which would mean that far more people should be considered for treatment if such a difference between arms is present. To this end, the research team has created a tool that is easy for clinicians to use, to establish who should be considered for treatment based on their risk, incorporating the blood pressure reading in both arms.

Research co-author Professor Victor Aboyans, head of the department of cardiology at the Dupuytren University Hospital in Limoges, France, said "We believe that a 10 mmHg difference can now reasonably be regarded as an upper limit of normal for systolic inter-arm blood pressure, when both arms are measured in sequence during routine clinical appointments. This information should be incorporated into future guidelines and clinical practice in assessing cardiovascular risk. It would mean many more people were considered for treatment that could reduce their risk of heart attack, stroke and death."

An interarm difference of greater than 10 mmHg occurs in 11 per cent of people with high blood pressure (hypertension) -- itself a known health risk -- and in four per cent of the general population.

https://www.sciencedaily.com/releases/2020/12/201221101208.htm

How hope can make you happier with your lot in life

December 16, 2020

Science Daily/University of East Anglia

Having hope for the future could protect people from risky behaviours such as drinking and gambling -- according to new research from the University of East Anglia.

Researchers studied 'relative deprivation' -- the feeling that other people have things better than you in life.

They wanted to find out why only some people experiencing this turn to escapist and risky behaviours such as drinking alcohol, taking drugs, over-eating or gambling, while others do not.

And they found that the answer lies in hope.

Postgraduate researcher Shahriar Keshavarz, from UEA's School of Psychology, said: "I think most people have experienced relative deprivation at some point in their lives. It's that feeling of being unhappy with your lot, the belief that your situation is worse than others, that other people are doing better than you.

"Roosevelt famously said that 'comparison is the thief of joy'. It's that feeling you have when a friend buys a new car, or your sister gets married, or a colleague finds a better job or has a better income.

"Relative deprivation can trigger negative emotions like anger and resentment, and it has been associated with poor coping strategies like risk taking, drinking, taking drugs or gambling.

"But not everyone scoring high on measures of relative deprivation makes these poor life choices. We wanted to find out why some people seem to cope better, or even use the experience to their advantage to improve their own situation.

"There is a lot of evidence to show that remaining hopeful in the face of adversity can be advantageous, so we wanted to see if hope can help people feel happier with their lot and buffer against risky behaviours."

The research team carried out two lab-based experiments with 55 volunteers. The volunteers were quizzed to find out how much they feel relative deprivation and hope.

The researchers also induced feelings of relative deprivation in the volunteers, by telling them how deprived they were compared to their peers, based on a questionnaire about their family income, age and gender.

They then took part in specially designed gambling games that involved risk-taking and placing bets with a chance to win real money.

Dr Piers Fleming, also from UEA's School of Psychology, said: "The aim of this part of the study was to see whether feeling relatively deprived -- elicited by the knowledge that one has less income than similar others -- causes greater risk-taking among low-hopers and decreased risk-taking among high-hopers.

"We looked at the people who scored high for relative deprivation, the ones that thought their situation in life was worse than those around them. And we looked at those who also scored high for hope.

"We found that the volunteers who scored high for hope, were much less likely to take risks in the game. Those who weren't too hopeful, were a lot more likely to take risks."

Another experiment looked at whether hope helped people in the real world. They worked with 122 volunteers who had gambled at least once in the last year. The volunteers took part in questionnaires to gauge how hopeful they are, whether they feel relatively deprived and to measure problem gambling.

Of the participants, 33 had no gambling problems (27 per cent), 32 had low level of problems (26 per cent), 46 had moderate level of problems leading to some negative consequences (38 per cent) and 11 were problem gamblers with a possible loss of control (9 per cent).

Mr Keshavarz said: "When we looked at these scores compared to scores for hope and relative deprivation, we found that increased hope was associated with a decreased likelihood of losing control of gambling behaviour -- even in those who experienced relative deprivation.

"Interestingly, our study found no significant relation between hope and gambling severity among relatively privileged persons. We don't know why this is, but it could be that they are gambling recreationally or better able to stop when the fun stops."

The research team say that nurturing hope in people who are unhappy with their lot could protect against harmful behaviours like drinking and gambling.

https://www.sciencedaily.com/releases/2020/12/201216104631.htm

Three pillars of mental health: Good sleep, exercise, raw fruits and veggies

December 16, 2020

Science Daily/University of Otago

Getting good quality sleep, exercising, and eating more raw fruits and vegetables predicts better mental health and well-being in young adults, a University of Otago study has found.

The study, published in Frontiers in Psychology, surveyed more than 1100 young adults from New Zealand and the United States about their sleep, physical activity, diet, and mental health.

Lead author Shay-Ruby Wickham, who completed the study as part of her Master of Science, says the research team found sleep quality, rather than sleep quantity, was the strongest predictor of mental health and well-being.

"This is surprising because sleep recommendations predominantly focus on quantity rather than quality. While we did see that both too little sleep -- less than eight hours -- and too much sleep -- more than 12 hours -- were associated with higher depressive symptoms and lower well-being, sleep quality significantly outranked sleep quantity in predicting mental health and well-being.

"This suggests that sleep quality should be promoted alongside sleep quantity as tools for improving mental health and well-being within young adults," Ms Wickham says.

Along with quality sleep, exercising, and eating more raw fruits and vegetables -- in that order -- were three modifiable behaviours which correlated with better mental health and well-being in young adults.

Depressive symptoms were lowest for young adults who slept 9.7 hours per night, and feelings of well-being were highest for those who slept 8 hours per night.

Well-being was highest for young adults who ate 4.8 servings of raw fruit and vegetables per day; those who ate less than two servings, and also more than eight servings, reported lower feelings of well-being.

"Sleep, physical activity, and a healthy diet can be thought of as three pillars of health, which could contribute to promoting optimal well-being among young adults, a population where the prevalence of mental disorders is high and well-being is suboptimal," Ms Wickham says.

Senior author, Associate Professor Tamlin Conner, of the Department of Psychology, says most prior research examines these health behaviours in isolation of each other.

"We showed that they are all important for predicting which young adults are flourishing versus suffering."

She also stressed the study's findings were correlations only.

"We didn't manipulate sleep, activity, or diet to test their changes on mental health and well-being. Other research has done that and has found positive benefits. Our research suggests that a 'whole health' intervention prioritising sleep, exercise, and fruit and vegetable intake together, could be the next logical step in this research," she says.

https://www.sciencedaily.com/releases/2020/12/201216094647.htm

New insights about depression

Researchers find links between inflammation, menopause, and depressive disorder

December 14, 2020

Science Daily/UT Southwestern Medical Center

Recently published UT Southwestern research reveals new insights about risk factors for depression based on data from a landmark longitudinal study focused on heart disease.

One study, published in the Journal of Clinical Psychiatry, shows a link between an inflammatory molecule in the blood and a person's likelihood of depressive symptoms. The other study, in the journal Maturitas, indicates which symptoms of menopause are most predictive of depression.

Both studies are based on data from the Dallas Heart Study (DHS), which since 2000 has tracked the health of thousands of participants with the goal of improving the diagnosis, prevention, and treatment of heart disease.

"The DHS dataset is an extraordinary resource at UT Southwestern," says Sherwood Brown, M.D., Ph.D., senior author of both papers and professor of psychiatry and vice chair for clinical research at UTSW.

The first two years of the study, more than 6,000 residents of Dallas County completed a detailed medical survey; 3,500 of them, aged 30 to 65, provided blood samples and underwent imaging studies. The DHS put particular emphasis on recruiting a diverse group; more than half of all participants were African American and 17 percent were Hispanic.

In the process of collecting information, data useful for studying other medical conditions was amassed. Brown immediately saw the utility for the DHS data in his own work on depression.

Inflammation and depression

Depression is estimated to affect 4.4 percent of the world's population, making it one of the leading causes of disability. Researchers have struggled to understand all the molecular changes in the body that accompany major depressive disorder. More than 20 years ago, clinicians found that a pro-inflammatory drug used to treat some diseases could cause depression. Since that time, researchers including Brown have wondered about the link between inflammatory molecules and depression.

To that end, Brown and Samara Huckvale -- an undergraduate at Columbia University who as a high school student worked in Brown's lab in 2019 through UT Southwestern's STARS (Science Teacher Access to Resources at Southwestern) Summer Research Program -- analyzed data on 3,033 adults who had provided blood samples and completed a depression screening questionnaire as part of the DHS. The STARS Program, begun in 1991, provides summer research opportunities to high school students.

They discovered that levels of GlycA, an inflammatory molecule that's not routinely tested for in patients, correlated with the severity of depressive symptoms. Even after controlling for factors such as sex, ethnicity, antidepressant use, education, and body mass index, GlycA levels remained associated with depression severity.

"This study suggests that maybe we could predict or diagnose depression based on inflammatory scores," says Huckvale, who aspires to be a chemist. "Or maybe eventually we'll be able to design therapies that actually target this inflammation to treat depression."

Brown, who holds the Lou and Ellen McGinley Distinguished Chair in Psychiatric Research and the Aradine S. Ard Chair in Brain Science, adds that he'd like to study whether GlycA levels can predict how well a treatment for depression works or help guide the best antidepressants for particular patients. He'd also like to follow patients over time to gauge whether GlycA levels rise before or after the onset of depression symptoms.

Menopause and depression

In the Maturitas paper, Brown and his colleagues used DHS data to study menopausal women, a group known to have an increased risk of depression.

Previous studies have found a correlation between the most common symptoms of menopause -- hot flashes, night sweats, and sleep disturbances -- and the onset of depression. Menopause also causes sexual symptoms, including vaginal dryness and low libido, but few studies have looked at the association between these symptoms and depression.

In the study, Brown and colleagues analyzed DHS data on 384 women aged 37 to 73 years old who self-reported being in menopause. Sixty-four percent of the women were non-Hispanic Black, 26.8 percent were non-Hispanic white, and 9.11 percent were Hispanic.

"There are very different cultural and ethnic experiences around menopause, so it was important to us to look at a very diverse sample of women," says Michael Xincheng Ji, co-first author of the study and a fourth-year UTSW medical student.

As part of the Dallas Heart Study, the women reported whether they had symptoms classically associated with menopause, which the researchers grouped into vasomotor, psychosocial, physical, or sexual symptoms. In addition, each woman completed the Quick Inventory of Depressive Symptomatology-Self Report survey (QIDS-SR), which gauged the presence of depression symptoms.

The prevalence of sexual symptoms of menopause was positively associated with a higher score on the QIDS-SR. This association remained even after excluding women who were taking antidepressants, and there was also an association between psychosocial symptoms of menopause and the QIDS-SR score. No association was found between vasomotor or physical symptoms and the QIDS-SR score, and ethnicity was not a strong predictor of the depression symptoms.

"Recognizing patterns in who is most likely to develop depression is really important to help guide our screening efforts," says Sydney Singleterry, co-first author of the new work and a fourth-year UTSW medical student.

"What we hope is that these findings make clinicians think about the possibility of depression when they hear a woman reporting these symptoms," says Brown, also a member of the Peter O'Donnell Jr. Brain Institute.

https://www.sciencedaily.com/releases/2020/12/201214150337.htm

The power of validation in helping people stay positive

Supporting someone's negative emotions can help foster a positive outlook

December 14, 2020

Science Daily/Ohio State University

Telling a distressed friend or family member something as simple as "I understand why you feel that way" can go a long way toward helping loved ones feel better, new research suggests.

In the study, participants described to the researchers a real-life incident that made them angry.

When researchers didn't show support or understanding for the anger participants were describing, the story-tellers showed declines in positive emotions. But when the researchers validated what the participants were saying, their positive emotions were protected and stayed the same.

Similarly, study participants reported dips in their overall mood as they recalled the anger-provoking event, and only those who were validated reported a recovery of mood back to their starting point.

There was no significant difference found in participants' negative emotions -- a result that speaks to the value of focusing on protecting positivity, said Jennifer Cheavens, senior author of the study and a professor of psychology at The Ohio State University.

"We have underestimated the power of positive emotions. We spend so much time thinking about how to remedy negative emotions, but we don't spend much time thinking about helping people harness and nurture positive emotions," Cheavens said.

"It's really important to help people with their depression, anxiety and fear, but it's also important to help people tap into curiosity, love, flexibility and optimism. People can feel sad and overwhelmed, and also hopeful and curious, in the same general time frame."

The study is published online in the Journal of Positive Psychology.

In three experiments, the researchers assessed the effects of validation and invalidation on what are known clinically as positive and negative affect. Positive affect refers to positive emotions and expression that Cheavens said allow us to be curious, connected and flexible in our thinking. Negative affect, on the other hand, refers to negative emotions and expression ranging from disgust to fear to sadness.

A total of 307 undergraduate students participated in the experiments. The students completed questionnaires measuring positive and negative affect at the beginning and end of the study and overall mood at several time points during the experiments.

Researchers asked participants to think and write for five minutes about a time when they felt intense anger, and then verbally describe those experiences to a researcher. Based on randomized assignments, the experimenter either validated or invalidated their angry feelings.

The participants' experiences with anger covered a wide range: roommate troubles, unfaithful romantic partners, being the victim of a theft or getting mad at their parents.

Experimenters listening to their stories used flexible scripts to respond. Validating comments included such phrases as "Of course you'd be angry about that" or "I hear what you're saying and I understand you feel angry."

Invalidating responses ranged from "That doesn't sound like anger" to "Why would that make you so angry?"

Results showed that all participants had a decrease in positive affect while they were thinking and writing about being angry. However, when they started describing the situation to experimenters, the validated participants' positive affect matched or even exceeded their baseline measures. The positive affect scores for those who were invalidated did not recover while talking with the experimenters.

Based on five measures of mood in two of the three studies, participants' mood consistently darkened as they considered what made them angry. Validated participants' moods were restored to normal, but the invalidated students' moods generally continued to get worse.

The research team conducted the studies with plans to apply the results in a therapy setting. But the findings are relevant for relationships as well, Cheavens said.

"When you process negative emotions, that negative affect gets turned on. But if someone validates you, it keeps your positive affect buffered. Validation protects people's affect so they can stay curious in interpersonal interactions and in therapy," she said.

"Adding validation into therapy helps people feel understood, and when we feel understood we can receive feedback on how we also might change. But it's not a uniquely clinical thing -- often the same ways you make therapy better are ways you make parenting, friendships and romantic relationships better.

https://www.sciencedaily.com/releases/2020/12/201214123517.htm

Gut microbiota plays a role in brain function and mood regulation

December 11, 2020

Science Daily/Institut Pasteur

Depression is a mental disorder that affects more than 264 million people of all ages worldwide. Understanding its mechanisms is vital for the development of effective therapeutic strategies. Scientists from the Institut Pasteur, Inserm and the CNRS recently conducted a study showing that an imbalance in the gut bacterial community can cause a reduction in some metabolites, resulting in depressive-like behaviors. These findings, which show that a healthy gut microbiota contributes to normal brain function, were published in Nature Communications on December 11, 2020.

The bacterial population in the gut, known as the gut microbiota, is the largest reservoir of bacteria in the body. Research has increasingly shown that the host and the gut microbiota are an excellent example of systems with mutually beneficial interactions. Recent observations also revealed a link between mood disorders and damage to the gut microbiota. This was demonstrated by a consortium of scientists from the Institut Pasteur, the CNRS and Inserm, who identified a correlation between the gut microbiota and the efficacy of fluoxetine, a molecule frequently used as an antidepressant. But some of the mechanisms governing depression, the leading cause of disability worldwide, remained unknown.

Using animal models, scientists recently discovered that a change to the gut microbiota brought about by chronic stress can lead to depressive-like behaviors, in particular by causing a reduction in lipid metabolites (small molecules resulting from metabolism) in the blood and the brain.

These lipid metabolites, known as endogenous cannabinoids (or endocannabinoids), coordinate a communication system in the body which is significantly hindered by the reduction in metabolites. Gut microbiota plays a role in brain function and mood regulation

Endocannabinoids bind to receptors that are also the main target of THC, the most widely known active component of cannabis. The scientists discovered that an absence of endocannabinoids in the hippocampus, a key brain region involved in the formation of memories and emotions, resulted in depressive-like behaviors.

The scientists obtained these results by studying the microbiotas of healthy animals and animals with mood disorders. As Pierre-Marie Lledo, Head of the Perception and Memory Unit at the Institut Pasteur (CNRS/Institut Pasteur) and joint last author of the study, explains: "Surprisingly, simply transferring the microbiota from an animal with mood disorders to an animal in good health was enough to bring about biochemical changes and confer depressive-like behaviors in the latter."

The scientists identified some bacterial species that are significantly reduced in animals with mood disorders. They then demonstrated that an oral treatment with the same bacteria restored normal levels of lipid derivatives, thereby alleviating the depressive-like behaviors. These bacteria could therefore serve as an antidepressant. Such treatments are known as "psychobiotics."

"This discovery shows the role played by the gut microbiota in normal brain function," continues Gérard Eberl, Head of the Microenvironment and Immunity Unit (Institut Pasteur/Inserm) and joint last author of the study. If there is an imbalance in the gut bacterial community, some lipids that are vital for brain function disappear, encouraging the emergence of depressive-like behaviors. In this particular case, the use of specific bacteria could be a promising method for restoring a healthy microbiota and treating mood disorders more effectively.

https://www.sciencedaily.com/releases/2020/12/201211115507.htm

Biological diversity evokes happiness

More bird species in their vicinity increase life satisfaction of Europeans as much as higher income

December 4, 2020

Science Daily/German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig

A high biodiversity in our vicinity is as important for life satisfaction as our income, scientists found. All across Europe, the individual enjoyment of life correlates with the number of surrounding bird species. An additional 10% of bird species therefore increases the Europeans' life satisfaction as much as a comparable increase in income. Nature conservation thus constitutes an investment in human well-being.

Under the current pandemic conditions, activities out in nature are a popular pastime. The beneficial effects of a diverse nature on people's mental health have already been documented by studies on a smaller scale. Scientists of the Senckenberg Gesellschaft für Naturforschung, the iDiv, and the University of Kiel now examined for the first time whether a diverse nature also increases human well-being on a Europe- wide scale.

To this end, the researchers used the data from the "2012 European quality of Life Survey" to study the connection between the species diversity in their surroundings and the life satisfaction in more than 26,000 adults from 26 European countries. Species diversity was measured based on the diversity of avian species, as documented in the European breeding bird atlas.

"Europeans are particularly satisfied with their lives if their immediate surroundings host a high species diversity," explains the study's lead author, Joel Methorst, a doctoral researcher at the Senckenberg Biodiversity and Climate Research Centre, the iDiv, and the Goethe University in Frankfurt. "According to our findings, the happiest Europeans are those who can experience numerous different bird species in their daily life, or who live in near-natural surroundings that are home to many species."

Birds are well-suited as indicators of biological diversity, since they are among the most visible elements of the animate nature -- particularly in urban areas. Moreover, their song can often be heard even if the bird itself is not visible, and most birds are popular and people like to watch them. But there is also a second aspect that affects life satisfaction: the surroundings. A particularly high number of bird species can be found in areas with a high proportion of near-natural and diverse landscapes that hold numerous greenspaces and bodies of water.

"We also examined the socio-economic data of the people that were surveyed, and, much to our surprise, we found that avian diversity is as important for their life satisfaction as is their income," explains Prof. Dr. Katrin Böhning-Gaese, director of the Senckenberg Biodiversity and Climate Research Centre, professor at the Goethe University in Frankfurt am Main, and member of the iDiv. This result becomes particularly obvious when both values increase by ten percent. Fourteen additional bird species in the vicinity raise the level of life satisfaction at least as much as an extra 124 Euros per month in the household account, based on an average income of 1,237 Euro per month in Europe.

According to the study, a diverse nature therefore plays an important role for human well-being across Europe -- even beyond its material services. At the same time, the researchers draw attention to impending health-related problems. "The Global Assessment 2019 by the World Biodiversity Council IPBES and studies of avian species in agricultural landscapes in Europe clearly show that the biological diversity is currently undergoing a dramatic decline. This poses the risk that human well-being will also suffer from an impoverished nature. Nature conservation therefore not only ensures our material basis of life, but it also constitutes an investment in the well-being of us all," adds Methorst in conclusion.

https://www.sciencedaily.com/releases/2020/12/201204110246.htm

Drinking linked to a decline in brain health from cradle to grave

December 3, 2020

Science Daily/BMJ

The evidence for the harmful effects of alcohol on brain health is compelling, but now experts have pin-pointed three key time periods in life when the effects of alcohol are likely to be at their greatest.

Writing in The BMJ today, researchers in Australia and the UK say evidence suggests three periods of dynamic brain changes that may be particularly sensitive to the harmful effects of alcohol: gestation (from conception to birth), later adolescence (15-19 years), and older adulthood (over 65 years).

They warn that these key periods "could increase sensitivity to the effects of environmental exposures such as alcohol" and say harm prevention policies "must take the long view."

Globally, around 10% of pregnant women consume alcohol, with the rates considerably higher in European countries than the global average, they write.

Heavy alcohol use during pregnancy can cause fetal alcohol spectrum disorder, associated with widespread reductions in brain volume and cognitive impairment. But data suggest that even low or moderate alcohol consumption during pregnancy is significantly associated with poorer psychological and behavioural outcomes in offspring.

In terms of adolescence, more than 20% of 15-19 year olds in European and other high income countries report at least occasional binge drinking (defined as 60 g of ethanol on a single occasion), they add.

Studies indicate that the transition to binge drinking in adolescence is associated with reduced brain volume, poorer white matter development (critical for efficient brain functioning), and small to moderate deficits in a range of cognitive functions.

And in older people, alcohol use disorders were recently shown to be one of the strongest modifiable risk factors for all types of dementia (particularly early onset) compared with other established risk factors such as high blood pressure and smoking.

Although alcohol use disorders are relatively rare in older adults, the authors point out that even moderate drinking has been shown to be linked to a small but significant loss of brain volume in midlife, although further studies are needed to test whether these structural changes translate into functional impairment.

Furthermore, demographic trends may compound the effect of alcohol use on brain health, they write. For example, women are now just as likely as men to drink alcohol and experience alcohol related harms, and global consumption is forecast to rise further in the next decade.

The effects of the covid-19 pandemic on alcohol use and related harms are unclear, but alcohol use increased in the long term after other major public health crises, they add.

As such, they call for an integrated approach to harm reduction at all ages.

"Population based interventions such as guidelines on low risk drinking, alcohol pricing policies, and lower drink driving limits need to be accompanied by the development of training and care pathways that consider the human brain at risk throughout life," they conclude.

https://www.sciencedaily.com/releases/2020/12/201203200605.htm

Researchers find how stress and the circadian clock affect sleep

The findings could lead to the development of new therapies for sleep disorders caused by stress or a disturbed circadian rhythm

November 30, 2020

Science Daily/Nagoya University

A Nagoya University-led research team in Japan has found a new neural pathway that links the circadian clock, stress, and wakefulness in mammals. The team identified a neuron, called the corticotropin-releasing factor (CRF) neuron, that becomes excessively active when the mammal is under stress, which could trigger insomnia and other sleep disorders. Their findings were recently published in the journal Science Advances.

Living organisms exhibit a 24-hour oscillation called the circadian rhythm. In mammals, the central circadian clock, located in the brain's suprachiasmatic nucleus (SCN) neurons, regulates the sleep-wake cycle. However, in the event of life-threatening situations, the circadian rhythm signal is shut off to keep the animal awake so that it can escape from danger even when it would normally be time to sleep. Although the temporary shutoff of the sleep-wake cycle is necessary for survival, excessive or prolonged stress caused by such dangers can trigger insomnia and other sleep disorders.

"It is well-known that the circadian clock and stress have an effect on sleep, but it was unclear which neural pathway is crucial for the circadian regulation of sleep and wakefulness," says Dr. Daisuke Ono of the Research Institute of Environmental Medicine at Nagoya University. To determine the pathway, a Nagoya University research team led by Prof. Akihiro Yamanaka and Dr. Ono, in collaboration with Takashi Sugiyama at Olympus Corporation in Japan, conducted a study using mice.

The researchers focused on CRF neurons -- which are known to play a role in stress response -- that are located in the paraventricular nucleus of the hypothalamus. They investigated how sleep and wakefulness in mice would be affected when the CRF neurons were activated. The results showed that the activated CRF neurons kept the animals awake and made them move around vigorously, indicating that their wakefulness was promoted. The researchers also observed that CRF neurons remained active when the mice were awake, and that when the neurons' activity was suppressed, the animals' wakefulness and locomotor activities were reduced.

Further investigations also showed that inhibitory neurons in the SCN, called GABAergic neurons, play a significant role in regulating the activity of CRF neurons, and that the activation of CRF neurons stimulates orexin neurons in the lateral hypothalamus, which results in the promotion of wakefulness.

The team thus concluded that GABAergic neurons in the SCN control the activity of CRF neurons, which ultimately regulates the sleep-wake cycle. "We identified this neural pathway in mice, which are nocturnal animals. Further studies are required to elucidate how the nocturnal and diurnal difference is regulated in the brain," says Dr. Ono.

"In today's society, sleep disorders are a serious problem. We hope our finding will contribute to the development of new therapies for insomnia and other sleep disorders caused by stress or a disturbed circadian rhythm."

https://www.sciencedaily.com/releases/2020/11/201130113534.htm

Gut microbes: a key to normal sleep

November 30, 2020

Science Daily/University of Tsukuba

Researchers used a cocktail of antibiotics to deplete gut microbes in mice. They found that metabolites in the gut differed in these mice compared with controls. In particular, metabolic pathways involved in making important neurotransmitters like serotonin were affected. Additionally, these mice showed abnormal day-night distribution in sleep/wake patterns, particularly the amount of REM sleep, and frequent transitions between REM and non-REM sleep episodes.

With fall and winter holidays coming up, many will be pondering the relationship between food and sleep. Researchers led by Professor Masashi Yanagisawa at the University of Tsukuba in Japan hope they can focus people on the important middlemen in the equation: bacterial microbes in the gut. Their detailed study in mice revealed the extent to which bacteria can change the environment and contents of the intestines, which ultimately impacts behaviors like sleep.

The experiment itself was fairly simple. The researchers gave a group of mice a powerful cocktail of antibiotics for four weeks, which depleted them of intestinal microorganisms. Then, they compared intestinal contents between these mice and control mice who had the same diet. Digestion breaks food down into bits and pieces called metabolites. The research team found significant differences between metabolites in the microbiota-depleted mice and the control mice. As Professor Yanagisawa explains, "we found more than 200 metabolite differences between mouse groups. About 60 normal metabolites were missing in the microbiota-depleted mice, and the others differed in the amount, some more and some less than in the control mice."

The team next set out to determine what these metabolites normally do. Using metabolome set enrichment analysis, they found that the biological pathways most affected by the antibiotic treatment were those involved in making neurotransmitters, the molecules that cells in the brain use to communicate with each other. For example, the tryptophan-serotonin pathway was almost totally shut down; the microbiota-depleted mice had more tryptophan than controls, but almost zero serotonin. This shows that without important gut microbes, the mice could not make any serotonin from the tryptophan they were eating. The team also found that the mice were deficient in vitamin B6 metabolites, which accelerate production of the neurotransmitters serotonin and dopamine.

The team also analyzed how the mice slept by looking at brain activity in EEGs. They found that compared with the control mice, the microbiota-depleted mice had more REM and non-REM sleep at night -- when mice are supposed to be active -- and less non-REM sleep during the day -- when mice should be mostly sleeping. The number of REM sleep episodes was higher both during the day and at night, whereas the number of non-REM episodes was higher during the day. In other words, the microbiota-depleted mice switched between sleep/wake stages more frequently than the controls.

Professor Yanagisawa speculates that the lack of serotonin was responsible for the sleep abnormalities; however, the exact mechanism still needs to be worked out. "We found that microbe depletion eliminated serotonin in the gut, and we know that serotonin levels in the brain can affect sleep/wake cycles," he says. "Thus, changing which microbes are in the gut by altering diet has the potential to help those who have trouble sleeping."

So, this holiday season, when you're feeling sleepy after eating tryptophan-stuffed turkey, please don't forget to thank your gut microbes!

https://www.sciencedaily.com/releases/2020/11/201130113532.htm

Anxiety associated with faster Alzheimer's disease onset

November 24, 2020

Science Daily/Radiological Society of North America

Anxiety is associated with an increased rate of progression from mild cognitive impairment to Alzheimer's disease, according to a study being presented at the annual meeting of the Radiological Society of North America (RSNA).

Alzheimer's disease represents a major public health crisis worldwide. The number of deaths from the disease has more than doubled since 2000, and it is currently the fifth-leading cause of death among individuals over 65 in the U.S.

Many people with Alzheimer's disease first suffer from mild cognitive impairment, a decline in cognitive abilities like memory and thinking skills that is more rapid than normally associated with aging. Anxiety has been frequently observed in patients with mild cognitive impairment, although its role in disease progression is not well understood.

"We know that volume loss in certain areas of the brain is a factor that predicts progression to Alzheimer's disease," said study senior author Maria Vittoria Spampinato, M.D., professor of radiology at the Medical University of South Carolina (MUSC) in Charleston. "In this study, we wanted to see if anxiety had an effect on brain structure, or if the effect of anxiety was independent from brain structure in favoring the progression of disease."

The study group included 339 patients, average age of 72 years, from the Alzheimer's Disease Neuroimaging Initiative 2 cohort. Each person had a baseline diagnosis of mild cognitive impairment; 72 progressed to Alzheimer's disease while 267 remained stable.

The researchers obtained brain MRIs to determine the baseline volumes of the hippocampus and the entorhinal cortex, two areas important to forming memories. They also tested for the presence of the ApoE4 allele, the most prevalent genetic risk factor for Alzheimer's disease. Anxiety was measured with established clinical surveys.

As expected, patients who progressed to Alzheimer's disease had significantly lower volumes in the hippocampus and the entorhinal cortex and greater frequency of the ApoE4 allele. Most notably though, the researchers found that anxiety was independently associated with cognitive decline.

"Mild cognitive impairment patients with anxiety symptoms developed Alzheimer's disease faster than individuals without anxiety, independently of whether they had a genetic risk factor for Alzheimer's disease or brain volume loss," said study first author Jenny L. Ulber, a medical student at MUSC.

The link between anxiety symptoms and a faster progression to Alzheimer's disease presents an opportunity for improving the screening and management of patients with early mild cognitive impairment, the researchers said.

"We need to better understand the association between anxiety disorders and cognitive decline," Dr. Spampinato said. "We don't know yet if the anxiety is a symptom -- in other words, their memory is getting worse and they become anxious -- or if anxiety contributes to cognitive decline. If we were able in the future to find that anxiety is actually causing progression, then we should more aggressively screen for anxiety disorders in the elderly."

"The geriatric population is routinely screened for depression in many hospitals, but perhaps this vulnerable population should also be assessed for anxiety disorders," Ulber added. "Middle-aged and elderly individuals with high level of anxiety may benefit from intervention, whether it be pharmacological or cognitive behavioral therapy, with the goal of slowing cognitive decline."

The study was based on MRI scans done at one point in time. For future research, the team would like to study MRIs obtained after the initial scan to better understand the connection between anxiety and brain structure.

"We're now interested in looking at changes over time to see if anxiety has an effect one way or the other on how fast the brain damage progresses," Dr. Spampinato said. "We will also take a closer look at gender differences in the association between anxiety and cognitive decline."

https://www.sciencedaily.com/releases/2020/11/201124092156.htm

Everyday activities enhance personal well-being

November 25, 2020

Science Daily/Karlsruher Institut für Technologie (K

Physical activity makes happy and is important to maintain psychic health. Researchers of Karlsruhe Institute of Technology (KIT) and the Central Institute of Mental Health (CIMH) in Mannheim studied the brain regions which play a central role in this process. Their findings reveal that even everyday activities, such as climbing stairs, significantly enhance well-being, in particular of persons susceptible to psychiatric disorders. The study is published in Science Advances.

Exercise enhances physical well-being and mental health. However, impacts of everyday activities, such as climbing stairs, walking, or going to the tram station instead of driving, on a person's mental health have hardly been studied so far. For example, it is not yet clear which brain structures are involved. A team of the Central Institute of Mental Health (CIMH) in Mannheim, KIT's Institute of Sports and Sports Science, and the GIScience / Geoinformatics Research Group of Heidelberg University has now studied everyday activities that make up the highest share of our daily exercise. "Climbing stairs every day may help us feel awake and full of energy. This enhances well-being," the study's first authors explain. These are Dr. Markus Reichert who conducts research at CIMH and KIT and Dr. Urs Braun, Head of the Complex Systems Research Group of the Psychiatry and Psychotherapy Clinic of CIMH.

The research findings are of particular relevance in the current situation with Corona restrictions and the coming winter. "Currently, we are experiencing strong restrictions of public life and social contacts, which may adversely affect our well-being," Professor Heike Tost, Head of the Systems Neuroscience Psychiatry Research Group of the Psychiatry and Psychotherapy Clinic, says. "To feel better, it may help to more often climb stairs."

Everyday Activities Enhance Alertness and Physical Energy 

"For our studies, we newly combined various research methods in everyday life and at the laboratory," says Professor Ulrich Ebner-Priemer, Head of the mHealth Methods in Psychiatry Research Group, Deputy Head of IfSS, and Head of the Mental mHealth Lab of KIT. Among the methods used were ambulant assessments with movement sensors as well as smartphone surveys on the well-being that were triggered by geolocation data as soon as the subjects moved.

67 persons were subjected to ambulant assessments to determine the impact of everyday activity on alertness for seven days. It was found that the persons felt more alert and were bursting with even more energy directly after the activity. Alertness and energy were proved to be important components of well-being and psychic health of the participants.

Brain Regions for Everyday Activities and Well-being Identified

These analyses were combined with magnetic resonance tomography at CIMH for another group of 83 persons. The volume of gray brain matter was measured to find out which brain areas play a role in these everyday processes. It was found that the subgenual cingulate cortex, a section of the cerebral cortex, is important to the interaction between everyday activity and affective well-being. It is in this brain region where emotions and resistance to psychiatric disorders are regulated. The authors identified this brain region to be a decisive neural correlate that mediates the relationship between physical activity and subjective energy. "Persons with a smaller volume of gray brain matter in this region and a higher risk of psychiatric disorders felt less full of energy when they were physically inactive," Heike Tost describes the results. "After everyday activity, however, these persons felt even more filled with energy than persons with a larger brain volume."

Specific Use of Physical Activity in Everyday Life

Professor Andreas Meyer-Lindenberg, Director of CIMH and Medical Director of the Psychiatry and Psychotherapy Clinic, concludes that "the results suggest that physical activity in everyday life is beneficial to well-being, in particular in persons susceptible to psychiatric disorders." In future, the findings of the study might be used in a smartphone app that will motivate users to be active to enhance their well-being in case of decreasing energy." It remains to be studied whether everyday activities may change the well-being and the brain volume and how these results may help prevent and treat psychiatric disorders," Urs Braun says.

https://www.sciencedaily.com/releases/2020/11/201125104348.htm

High blood pressure in midlife is linked to increased brain damage in later life

November 25, 2020

Science Daily/European Society of Cardiology

Higher than normal blood pressure is linked to more extensive brain damage in the elderly, according to a new study published today (Thursday) in the European Heart Journal.

In particular, the study found that there was a strong association between diastolic blood pressure (the blood pressure between heart beats) before the age of 50 and brain damage in later life, even if the diastolic blood pressure was within what is normally considered to be a healthy range.

The findings come from a study of 37,041 participants enrolled in UK Biobank, a large group of people recruited from the general population aged between 40 and 69 years, and for whom medical information, including MRI brain scans was available.

The research, carried out by Dr Karolina Wartolowska, a clinical research fellow at the Centre for Prevention of Stroke and Dementia, University of Oxford, UK, looked for damage in the brain called "white matter hyperintensities" (WMH). These show up on MRI brain scans as brighter regions and they indicate damage to the small blood vessels in the brain that increases with age and blood pressure. WMH are associated with an increased risk of stroke, dementia, physical disabilities, depression and a decline in thinking abilities.

Dr Wartolowska said: "Not all people develop these changes as they age, but they are present in more than 50% of patients over the age of 65 and most people over the age of 80 even without high blood pressure, but it is more likely to develop with higher blood pressure and more likely to become severe."

Information on the participants was collected when they enrolled in UK Biobank between March 2006 and October 2010, and follow-up data, including MRI scans, were acquired between August 2014 and October 2019. The researchers adjusted the information to take account of factors such as age, sex, risk factors such as smoking and diabetes, and diastolic as well as systolic blood pressure. Systolic blood pressure is the maximum blood pressure reached each time the heart beats and is the top number in blood pressure measurements.

"To compare the volume of white matter hyperintensities between people and to adjust the analysis for the fact that people's brains vary slightly in size, we divided the volume of WMH by the total volume of white matter in the brain. In that way, we could analyse the WMH load, which is the proportion of the WMH volume to the total volume of white matter," said Dr Wartolowska.

The researchers found that a higher load of WMH was strongly associated with current systolic blood pressure, but the strongest association was for past diastolic blood pressure, particularly when under the age of 50. Any increase in blood pressure, even below the usual treatment threshold of 140 mmHg for systolic and below 90 mmHg for diastolic, was linked to increased WMH, especially when people were taking medication to treat high blood pressure.*

For every 10mmHg increase in systolic blood pressure above the normal range, the proportion of WMH load increased by an average (median) of 1.126-fold and by 1.106-fold for every 5mmHg increase in diastolic blood pressure. Among the top 10% of people with the greatest WMH load, 24% of the load could be attributed to having a systolic blood pressure above 120mmHg, and 7% could be attributed to having diastolic blood pressure above 70mmHg, which reflects the fact that there is a greater incidence of elevated systolic rather than diastolic blood pressure in older patients.

Dr Wartolowska said: "We made two important findings. Firstly, the study showed that diastolic blood pressure in people in their 40s and 50s is associated with more extensive brain damage years later. This means that it is not just the systolic blood pressure, the first, higher number, but the diastolic blood pressure, the second, lower number, that is important to prevent brain tissue damage. Many people may think of hypertension and stroke as diseases of older people, but our results suggest that if we would like to keep a healthy brain well into our 60s and 70s, we may have to make sure our blood pressure, including the diastolic blood pressure, stays within a healthy range when we are in our 40s and 50s.

"The second important finding is that any increase in blood pressure beyond the normal range is associated with a higher amount of white matter hyperintensities. This suggests that even slightly elevated blood pressure before it meets the criteria for treating hypertension has a damaging effect on brain tissue.

"Our results suggest that to ensure the best prevention of white matter hyperintensities in later life, control of diastolic blood pressure, in particular, may be required in early midlife, even for diastolic blood pressure below 90mmHg, whilst control of systolic blood pressure may be more important in late life. The long time interval between the effects of blood pressure in midlife and the harms in late life emphasises how important it is to control blood pressure long-term, and that research has to adapt to consider the very long-term effects of often asymptomatic problems in midlife."

Potential mechanisms for the development of WMH include damage to the delicate blood vessels in the brain through sustained elevated pressures over time that directly cause damage to the blood vessels; this leads to the lining of the vessels becoming leaky and results in WMH. Alternatively, diastolic pressure might cause large blood vessels to become stiffer with time, which increases pulsations of blood pressure to the brain; this causes high blood pressure with each heart beat, rapid changes in blood pressure, and blood flow that is too low between heart beats, resulting in damage to white matter.

As MRI scans were only available at one time point, the researchers could not quantify the progression of WMH directly. Other limitations include that further analysis is needed to identify differences in different regions of white matter, and that although the researchers showed associations with smoking and diabetes, the potential complex interaction between risk factors, which also include high cholesterol levels, obesity and kidney problems, require further investigation.

Notes: 

* Patients with a 'low normal' blood pressure of 120/70mmHg were used as the 'reference group' with whom the researchers compared the other groups of patient in this analysis. Consistent with most guidelines, the researchers referred to people with blood pressure over 140/90 mmHg as 'hypertensive' and requiring treatment, and those between 140/90 and 130/80 mmHg as 'pre-hypertensive'. People with blood pressure below the pre-hypertensive values were referred to as 'high normotensive' and those with values below 120/70 as 'low normotensive'.

https://www.sciencedaily.com/releases/2020/11/201125190737.htm

Stress in pregnancy may influence baby brain development

November 24, 2020

Science Daily/University of Edinburgh

Infants' brains may be shaped by levels of stress their mother experiences during pregnancy, a study has revealed.

Stress levels in mothers -- measured by a hormone linked to anxiety and other health problems -- is related to changes in areas of the infant brain associated with emotional development, the study suggests.

Doctors say the findings highlight the urgent need for women to be better supported with their mental and physical health before and during pregnancy, and could help them spot mums and babies who need help.

The experts add that pregnant women who feel stressed or unwell should seek help from their midwife or consultant and that with support, most health issues can be well managed in pregnancy.

Maternal stress is known to influence the development of the child's behaviour and ability to regulate its emotions as it grows. This is usually measured by questionnaires, which are not always reliable.

The new study is the first time that scientists have used an objective measure -- levels of the hormone cortisol -- in the mother to study links with baby brain development.

Cortisol is involved in the body's response to stress -- with higher levels indicating higher stress -- and also plays a role in fetal growth.

A research team led by the University of Edinburgh showed that levels of cortisol are linked to the development of the baby's amygdala, an area of the brain known to be involved in emotional and social development in childhood.

For the study, scientists took hair samples from 78 pregnant women to determine the women's levels of cortisol in the previous three months.

The women's babies underwent a series of brain scans using Magnetic Resonance Imaging, or MRI, a non-invasive scan that took place whilst the baby slept.

The researchers found that higher levels of cortisol in the mother's hair were linked to structural changes in the infants' amygdala as well as differences in brain connections.

Doctors say this could explain why children whose mothers experienced high levels of stress during pregnancy may be more likely to have emotional issues in later life.

They caution, however, that the study did not assess emotion in children.

The study was funded by the global children's charity, Theirworld, and is published in the journal eLife.

Lead researcher, Professor James Boardman, Director of the Jennifer Brown Research Laboratory at the MRC Centre for Reproductive Health at the University of Edinburgh, said: "Our findings are a call to action to detect and support pregnant women who need extra help during pregnancy as this could be an effective way of promoting healthy brain development in their babies."

Professor Rebecca Reynolds, Personal Chair of Metabolic Medicine at the University of Edinburgh, who co-led the study, said: "Thankfully, psychological treatments are very successful at helping mothers and children and we hope that our findings could guide therapies in future to help spot those who might be most in need of support."

Sarah Brown, Chair of Theirworld, said: "This research highlights how important it is to support women's mental health during pregnancy to ensure that their needs are met and that their babies have the best start in life. Helping mothers cope with stress is an important step to ensure both mum and baby thrive."

https://www.sciencedaily.com/releases/2020/11/201124111105.htm

Cocoa flavanols boost brain oxygenation, cognition in healthy adults

November 24, 2020

Science Daily/University of Illinois at Urbana-Champaign, News Bureau

The brains of healthy adults recovered faster from a mild vascular challenge and performed better on complex tests if the participants consumed cocoa flavanols beforehand, researchers report in the journal Scientific Reports. In the study, 14 of 18 participants saw these improvements after ingesting the flavanols.

Previous studies have shown that eating foods rich in flavanols can benefit vascular function, but this is the first to find a positive effect on brain vascular function and cognitive performance in young healthy adults, said Catarina Rendeiro, a researcher and lecturer in nutritional sciences at the University of Birmingham who led the research with University of Illinois at Urbana-Champaign psychology professors Monica Fabiani and Gabriele Gratton.

"Flavanols are small molecules found in many fruits and vegetables, and cocoa, too," Rendeiro said. "They give fruits and vegetables their bright colors, and they are known to benefit vascular function. We wanted to know whether flavanols also benefit the brain vasculature, and whether that could have a positive impact on cognitive function."

The team recruited adult nonsmokers with no known brain, heart, vascular or respiratory disease, reasoning that any effects seen in this population would provide robust evidence that dietary flavanols can improve brain function in healthy people.

The team tested the 18 participants before their intake of cocoa flavanols and in two separate trials, one in which the subjects received flavanol-rich cocoa and another during which they consumed processed cocoa with very low levels of flavanols. Neither the participants nor researchers knew which type of cocoa was consumed in each of the trials. This double-blind study design prevents researchers' or participants' expectations from affecting the results.

About two hours after consuming the cocoa, participants breathed air with 5% carbon dioxide -- about 100 times the normal concentration in air. This is a standard method for challenging brain vasculature to determine how well it responds, Gratton said.

The body typically reacts by increasing blood flow to the brain, he said.

"This brings in more oxygen and also allows the brain to eliminate more carbon dioxide," he said.

With functional near-infrared spectroscopy, a technique that uses light to capture changes in blood flow to the brain, the team measured oxygenation in the frontal cortex, a brain region that plays a key role in planning, regulating behavior and decision-making.

"This allows you to measure how well the brain defends itself from the excess carbon dioxide," Fabiani said.

Researchers also challenged participants with complex tasks that required them to manage sometimes contradictory or competing demands.

Most of the participants had a stronger and faster brain oxygenation response after exposure to cocoa flavanols than they did at baseline or after consuming cocoa lacking flavanols, the researchers found.

"The levels of maximal oxygenation were more than three times higher in the high-flavanol cocoa versus the low-flavanol cocoa, and the oxygenation response was about one minute faster," Rendeiro said.

After ingesting the cocoa flavanols, participants also performed better on the most challenging cognitive tests, correctly solving problems 11% faster than they did at baseline or when they consumed cocoa with reduced flavanols. There was no measurable difference in performance on the easier tasks, however.

"This suggests that flavanols might only be beneficial during cognitive tasks that are more challenging," Rendeiro said.

Participants varied in their responses to cocoa flavanols, the researchers found.

"Although most people benefited from flavanol intake, there was a small group that did not," Rendeiro said. Four of the 18 study subjects had no meaningful differences in brain oxygenation response after consuming flavanols, nor did their performance on the tests improve.

"Because these four participants already had the highest oxygenation responses at baseline, this may indicate that those who are already quite fit have little room for improvement," Rendeiro said. "Overall, the findings suggest that the improvements in vascular activity after exposure to flavanols are connected to the improvement in cognitive function."

https://www.sciencedaily.com/releases/2020/11/201124092154.htm