Relaxation response may reduce blood pressure by altering expression of a set of genes
of genes
Researchers identified genes and biological pathways linked to immune regulation, metabolism, and circadian rhythm in people who reduced their hypertension after eight-week relaxation response training
April 4, 2018
Science Daily/Beth Israel Deaconess Medical Center
A new study has identified genes associated with the body's response to relaxation techniques and sheds light on the molecular mechanisms by which certain interventions may work to lower blood pressure.
High blood pressure -- or hypertension -- is a major risk factor for heart attack and stroke that affects as many as 100 million Americans and 1 billion people worldwide. Decades of research have demonstrated that the relaxation response -- the physiological and psychological opposite of the well-known fight-or-flight stress response that can be achieved through relaxation techniques like yoga or mediation -- can reduce blood pressure in people with hypertension. Exactly how these interventions act on the body to lower blood pressure remains unclear.
A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC), Massachusetts General Hospital (MGH), and the Benson-Henry Institute for Mind Body Medicine at MGH identified genes associated with the body's response to relaxation techniques and sheds light on the molecular mechanisms by which these interventions may work to lower blood pressure. The findings were published today in the Journal of Alternative and Complementary Medicine.
"Traditionally, hypertension is treated with pharmacologic therapy, but not all patients respond to drug therapy, and many experience treatment-limiting side effects," said co-senior author Randall Zusman, MD, Director of the Division of Hypertension at MGH's Corrigan Minehan Heart Center. "In these patients, alternative strategies are invaluable. In this study, we found that the relaxation response can successfully help reduce blood pressure in hypertensive patients who are not taking medication."
Towia Libermann, PhD, Director of the Genomics, Proteomics, Bioinformatics, and Systems Biology Center at BIDMC said, "To our knowledge, this is the first study to test such a mind-body intervention for a population of unmedicated adults with carefully documented, persistent hypertension, and this is the first study to identify gene expression changes specifically associated with the impact of a mind-body intervention on hypertension. Our results provide new insights into how integrative medicine -- especially mind-body approaches -- influences blood pressure control at the molecular level."
First described more than four decades ago by Herbert Benson, MD, Director Emeritus of the Benson Henry Institute and a co-author of the current study, the relaxation response is characterized by a set of measurable changes to the body, including decreased respiration rate and heart rate, all of which can be induced by mind-body techniques including meditation and yoga. Long-term relaxation response practice has been associated with increased brain cortical thickness and specific changes in gene expression.
In this study, Libermann, Zusman and colleagues enrolled 58 people with Stage 1 essential hypertension -- defined as having a systolic (top number) blood pressure between 140-159mm Hg and diastolic (bottom number) between 90-104mm Hg. Participants were either not taking medications to control their blood pressure or had tapered off them for five weeks prior to the outset of the study. Participants also filled out standardized questionnaires about stress, depression and anxiety.
Over the next eight weeks, participants attended eight weekly training sessions at which they were guided through mind-body interventions designed to elicit the relaxation response -- including diaphragmatic breathing, mantra repetition and mindfulness meditation -while passively ignoring intrusive thoughts. Participants were also given an audio CD that guided them through the same sequence for use at home once a day.
After the eight weeks of training, patients filled out the same stress, depression and anxiety questionnaires and had blood drawn for gene expression testing along with blood pressure measurement. Overall, 13 of the 24 participants who completed the eight-week intervention experienced a clinically relevant drop in blood pressure -- that is, specific reductions in both systolic and diastolic blood pressure readings that moved participants below 140/90 mm Hg, the clinical definition of stage 1 hypertension.
Patients who demonstrated significant reductions in both systolic and diastolic blood pressure -- enough so that their blood pressure was below the definition of Stage I essential hypertension -- were classified as "responders." Those whose blood pressure still fell within the definition of Stage I hypertension -- and those who did not see reduction in both numbers -- were classified as "non-responders."
When Libermann and colleagues ran gene expression analyses comparing blood samples from the two groups, they found that specific gene expression changes had occurred in the responders over the course of the eight-week relaxation response intervention that were not observed in the non-responders. Specifically, among responders the expression of 1,771 genes differed between the baseline blood tests and those taken after the eight weeks of relaxation response practice. Further, Libermann and colleagues determined that the reduction in blood pressure was correlated with genes linked to immune regulatory pathways, metabolism and glucose metabolism, cardiovascular system development and circadian rhythm.
"Interactive network analysis of the gene signature identified several molecules, particularly immune system-linked genes, as critical molecules for blood pressure reduction," said first author Manoj Bhasin, PhD, Co-Director of the Genomics, Proteomics, Bioinformatics, and Systems Biology Center at BIDMC.
"Our results suggest that the relaxation response reduced blood pressure -- at least in part -- by altering expression of genes in a select set of biological pathways," co-first author John Denninger, MD, PhD, Director of Research at the Benson-Henry Institute, noted. "Importantly, the changes in gene expression associated with this drop in blood pressure are consistent with the physical changes in blood pressure and inflammatory markers that one would anticipate and hope to observe in patients successfully treated for hypertension."
In addition to Zusman and Libermann, investigators included co-first author Manoj Bhasin and Marie Joseph of Beth Israel Deaconess Medical Center; co-first author John Denninger, Jeffrey Huffman, Halsey Niles, Emma Chad-Friedman, Roberta Goldman, Beverly Buczynski Kelley, Barbara Mahoney, Gregory Fricchione and Herbert Benson of Massachusetts General Hospital and Benson-Henry Institute for Mind Body Medicine at MGH; and Jeffery Dusek of Abbott Northwestern Hospital, Institute for Health and Healing.
https://www.sciencedaily.com/releases/2018/04/180404093929.htm
Human daily rhythms: Clocks vs light/dark cycle
April 3, 2018
Science Daily/University of Seville
A new study analyses daily primary activities of European laborers and the sources of social synchronization.
Should people living along a meridian be doing their basic activities (sleep/wake, working, eating, leaving home/coming home) at the same time? A 'yes' is an intuitive answer since solar noon happens simultaneously along the meridian. This phenomenon helps setting clock time. Therefore, a 'yes' is also pointing to clock synchronization, irrespective of latitude.
On a second thought we may understand that nobody gets to work at, say, 8am because it is four hours before noon, the bare meaning of clock ticking 8am. Instead the decision making process (whether 8am is fine, late or early) is driven by light conditions: did the Sun already rise? The answer to this question varies with latitude and season following the natural cycle of light and dark. Therefore, if this question influences human behaviour then people living along a meridian would not be doing their basic activities at the same time.
José María Martín Olalla, professor at University of Seville, addresses this issue in a paper entitled "Latitudinal trends in human primary activities: characterizing the winter day as a synchronizer" published in Scientific Reports, the Springer Nature open access megajournal. From time use surveys in 17 European countries and 2 American countries (located from 35º to 61º latitude) he characterizes laborer's primary activities and get them positioned along the daily and yearly cycle of light and dark.
Results show up latitudinal patterns tied to the light/dark cycle with the winter terminator as a source of synchronization for daily activities of laborers. Societies memorize the shortest photoperiod (daytime) of the year, the most challenging condition in one year. Winter photoperiod decreases by two hours from 40 to 54 degree latitude.
Winter sunrise (the later sunrise of the year and increasingly later with increasing latitude) triggers human activity in the morning year round and dominates morning trends. Its fingerprint can be traced on rising times, leaving home and working start times, all of them occur earlier with decreasing latitude. From 40 to 54 degree latitude, winter sunrise delays by one whole hour, the size of a standard time zone.
Winter sunset (the earliest sunset of the year, increasingly earlier with increasing latitude, it delays another whole hour from 54 to 40 degree latitude) triggers the reverse, shutdown process and dominates evening activities like stop working, coming home or dinning.
Two overturning sequences can also be identified. The first one occur at noon where lunch times exhibit both a meridional behaviour (tied to noon) and a latitudinal trend tied to the winter sunset. In this case people advance lunch times as latitude increases foreseeing the incoming dusk while people delay lunch times with decreasing latitude as light conditions do not worsen comparatively too much.
The second overturning sequence occurs at night and indoors: TV prime time marks and bedtimes are not tied to the winter sunset. Instead, they exhibit meridional behavior or trends weakly coupled to the winter sunrise. Societies are foreseeing the uprise in the following day.
The magnitude of the latitudinal gradient which dominates human activity can be comparatively traced out by observing how the terminator sweeps Europe in winter, when morning times are relatively similar as the sunrise terminator efficiently sweeps the continent, while evening times goes step by step following the sunset terminator.
Indirectly this study also inspects the role of time zone and time advance in human behaviour. The case of France, Belgium and Spain illustrates this issue. There, clocks are set one hour ahead of their physical time zone: that is an advanced clock, not an uncommon option for local time on Earth. Despite this time marks make perfect sense when properly tested against the LD cycle. That means people offset clock advancing by delaying time schedules apparently. In so doing they kept in phase with the LD cycle. This poses no harm to population. It only jeopardizes time comparisons, most notably in Spain due to its Southwestern most location. A rule of thumb valid for comparisons (both academic and non-academic) is subtracting one whole hour. That would convert "advanced clock" reading into standard time values.
https://www.sciencedaily.com/releases/2018/04/180403090052.htm
Frequency of alpha brain waves could be used to assess a person’s predisposition to pain
March 28, 2018
Science Daily/University of Birmingham
The frequency of alpha brain waves can be used as a measure of an individual’s vulnerability to developing and experiencing pain, researchers have discovered.
The personal experience of pain is highly variable among individuals, even in instances where the underlying injury is assessed to be identical.
Previous research has found some genetic factors influence pain susceptibility, but methods to accurately predict pain level consequent to medical intervention such as chemotherapy or surgery are lacking.
The objective of this study was to see if, from the resting brain activity of a healthy individual, it was possible to predict how much pain they would report once prolonged pain had been induced.
The researchers induced the pain using a capsaicin paste -- an ingredient found in hot chili peppers -- to study participants' left forearm and then heated it. Topical capsaicin exposure induces 'robust thermal hyperalgesia' -- a common symptom in chronic pain. All 21 participants in the study were induced in a state of prolonged pain for around an hour.
Using an electroencephalogram (EEG) -- a non-invasive test used to find problems related to the electrical activity of the brain -- the researchers found that across all 21 study participants, those who had a slower frequency of alpha brain waves recorded before the pain, reported being in much more pain than those who had a fast frequency of alpha brain waves.
The researchers also recorded the activity of alpha brain waves during the experience of pain, and if alpha frequency increased (relative to the no-pain condition) the individuals reported to be in less pain than when alpha pain decreased.
Co-senior author Dr Ali Mazaheri, of the University of Birmingham's Center for Human Brain Health, said: "Here we observe that an individual's alpha frequency can be used as a measure of an individual's predisposition to developing pain.
"This has a direct relevance to understanding what makes an individual prone to chronic pain after a medical intervention, such as surgery or chemotherapy.
"Potentially this means we could be able to identify which individuals are more likely to develop pain as a result of a medical procedure and take steps early on in formulating treatment strategies in patients likely to be predisposed to developing chronic pain."
Dr David Seminowicz and Andrew Furman, of the University of Maryland in the US, were also authors of the report.
Andrew Furman said: "Alpha frequency has been found to be slower in individuals who have experienced chronic pain. So the fact we observed that the slowing down of alpha activity as a result of pain correlated with the intensity of an individual's pain report was not that unexpected.
"What was very surprising though, was that prior to the pain -- that is pain-free alpha frequency -- could predict how much pain individuals would experience.
"This would suggest that it could be that the slowing of alpha activity in the chronic pain patients, isn't because of the pain, but rather these individuals had slow alpha frequency to begin with, and as such were more prone or vulnerable to developing pain."
The research, published in Neuroimage, was also carried out in collaboration with the Maryland Exercise and Robotics Center of Excellence in the US.
https://www.sciencedaily.com/releases/2018/03/180328092417.htm
Vagus nerve stimulation boosts post-stroke motor skill recovery
March 27, 2018
Science Daily/University of Texas at Dallas
Researchers have demonstrated a method to accelerate motor skill recovery after a stroke by helping the brain reorganize itself more quickly. In a preclinical study, the scientists paired vagus nerve stimulation with a physical therapy task aimed at improving the function of an upper limb in rodents. The results showed a doubled long-term recovery rate relative to current therapy methods.
In a preclinical study, the scientists paired vagus nerve stimulation (VNS) with a physical therapy task aimed at improving the function of an upper limb in rodents. The results showed a doubled long-term recovery rate relative to current therapy methods, not only in the targeted task but also in similar muscle movements that were not specifically rehabbed. Their work was recently published in the journal Stroke.
A clinical trial to test the technique in humans is underway in Dallas and 15 other sites across the country.
Dr. Michael Kilgard, associate director of the Texas Biomedical Device Center (TxBDC) and Margaret Forde Jonsson Professor of Neuroscience in the School of Behavioral and Brain Sciences, led the research team with Dr. Seth Hays, the TxBDC director of preclinical research and assistant professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science, and postdoctoral researcher Eric Meyers PhD'17.
"Our experiment was designed to ask this new question: After a stroke, do you have to rehabilitate every single action?" Kilgard said. "If VNS helps you, is it only helping with the exact motion or function you paired with stimulation? What we found was that it also improves similar motor skills as well, and that those results were sustained months beyond the completion of VNS-paired therapy."
Kilgard said the results provide an important step toward creating guidelines for standardized usage of VNS for post-stroke therapy.
"This study tells us that if we use this approach on complicated motor skills, those improvements can filter down to improve simpler movements," he said.
Building Stronger Cell Connections
When a stroke occurs, nerve cells in the brain can die due to lack of blood flow. An arm's or a leg's motor skills fail because, though the nerve cells in the limb are fine, there's no longer a connection between them and the brain. Established rehab methods bypass the brain's damaged area and enlist other brain cells to handle the lost functions. However, there aren't many neurons to spare, so the patient has a long-lasting movement deficit.
The vagus nerve controls the parasympathetic nervous system, which oversees elements of many unconscious body functions, including digestion and circulation. Electrical stimulation of the nerve is achieved via an implanted device in the neck. Already used in humans to treat depression and epilepsy, VNS is a well-documented technique for fine-tuning brain function.
The UT Dallas study's application of VNS strengthens the communication path to the neurons that are taking over for those damaged by stroke. The experiments showed a threefold-to-fivefold increase in engaged neurons when adding VNS to rehab.
"We have long hypothesized that VNS is making new connections in the brain, but nothing was known for sure," Hays said. "This is the first evidence that we are driving changes in the brain in animals after brain injury. It's a big step forward in understanding how the therapy works -- this reorganization that we predicted would underlie the benefits of VNS."
In anticipation of the technique's eventual use in humans, the team is working on an at-home rehab system targeting the upper limbs.
"We've designed a tablet app outlining hand and arm tasks for patients to interact with, delivering VNS as needed," Meyers said. "We can very precisely assess their performance and monitor recovery remotely. This is all doable at home."
Expanding the Possibilities for Therapy
The researchers are motivated in part by an understanding of the practical limitations of current therapeutic options for patients.
"If you have a stroke, you may have a limited time with a therapist," Hays said. "So when we create guidelines for a therapist, we now know to advise doing one complex activity as many times as possible, as opposed to a variety of activities. That was an important finding -- it was exciting that not only do we improve the task that we trained on, but also relatively similar tasks. You are getting generalization to related things, and you're getting sustained improvement months down the line."
For stroke patients, the opportunity to benefit from this technology may not be far off.
"A clinical trial that started here at UTD is now running nationwide, including at UT Southwestern," Kilgard said. "They are recruiting patients. People in Dallas can enroll now -- which is only fitting, because this work developed here, down to publishing this in a journal of the American Heart Association, which is based here in Dallas. This is a homegrown effort.
"The ongoing clinical trial is the last step in getting approved as an established therapy," Kilgard said. "We're hopefully within a year of having this be standard practice for chronic stroke."
https://www.sciencedaily.com/releases/2018/03/180327162606.htm
From lullabies to live concerts: How music and rhythm shape our social brains
March 27, 2018
Science Daily/Cognitive Neuroscience Society
A universal sign of motherhood is the lullaby. The world over, mothers sing to their babies, whether Twinkle Twinkle Little Star, their favorite song from the radio, or even random notes. This universality makes the simple lullaby a great window into the human mind. In a new study, cognitive neuroscientists found that lullabies soothe both moms and babies simultaneously, while playsongs increase babies' attention and displays of positive emotion toward their mothers.
The behavioral implications of music are vast, says Laura Cirelli of the University of Toronto Mississauga, who is presenting the new work on maternal singing at the 25th meeting of the Cognitive Neuroscience Society (CNS) in Boston today. "Infant brains must be able to track auditory events in a predictive manner to make sense of music," she explains, and many complex things are going on in their brains to make that possible.
From infancy to old age, music demands much from the human brain. Learning more about how we process music is helping scientists better understand perception, multisensory integration, and social coordination across the lifespan. Technological advancements -- for example, more portable electroencephalography (EEG) and electrophysiology set-ups and- are allowing cognitive neuroscientists to study music in a variety of situations, from mother-child interactions to live concert halls.
"Music and rhythm are human universals but do not appear to be shared by most other species," says Jessica Grahn of the University of Western Ontario who is chairing the CNS session on musical rhythm and who co-authored a new study of live music and brain rhythms. "Rhythm in particular is mysterious: We are sensitive to the 'beat' -- that steady, underlying pulse that we tap our foot or bob our head to -- from early in life. But, even after decades of trying, 'beat-tracking' algorithms can't approach anything like the automaticity and flexibility that humans show to feel the beat across different speeds, genres, and instruments."
Music for mom and baby
While working at a daycare one summer as an undergraduate student, Cirelli was at a playground when a 2-year-old girl asked her for help down the slide. The rest of the toddlers saw this, looked at each other, and excitedly ran over to line up and wait their turn. "I was amazed at the complexity of their social understanding at an age where they can't even tell us what they are thinking," she explains. This sent her down the path of exploring how sociality develops at a young age, and as a piano player and ballerina, the natural fit was to use music as a way to understand the social brain.
In her new study on lullabies, Cirelli and colleagues investigated how mothers adjust their infant-directed singing depending on their goal, to be soothing or to be playful. The participating mothers repeatedly sang Twinkle Twinkle to their babies who were sitting in a highchair facing them. The mothers alternated between singing in a playful way or a soothing manner. At the same time, researchers were tracking the mothers' and babies' arousal responses, measured through skin conductance and behavior. "When we are excited or stressed, arousal levels increase," Cirelli explains. "When we are calm, they decrease."
The researchers found that the moms' arousal levels were higher during playful compared to soothing song. And they found coordinated decreases in arousal for both the moms and babies as the soothing songs progressed. In the playful conditions, the babies' arousal levels remained stable and their attention to mother and displays of positive emotion increased. "The findings show the physiological and behavioral changes by mom and baby to different song styles."
This study builds on a growing body of work about the social implications of musical engagement with others. Cirelli points to past studies showing that when people move together in synchrony, they feel socially connected and are later more likely to help and cooperate with one another. And in a study of toddlers, she and colleagues had similar findings: 14-month-olds who bounced synchronously with unfamiliar adults helped those adults substantially more by retrieving dropped objects than those who bounced with them asynchronously. "Music is a tool that we can use to bring people together, and this starts in infancy."
Music for a live audience
Despite being able to listen to music from virtually anywhere in modern times, people will still pay hundreds of dollars for the opportunity attend a live musical performance. Why? This question helps drive forward the work of Grahn and Molly Henry, both of the University of Ontario.
In new work she will be presenting at the CNS meeting today, Henry used the LIVELab at McMaster University to test how the presence of live performers and an audience changes the experience of concert-goers at a neural level, Specifically, she and colleagues looked at brain rhythm synchronization.
A live band played in front of 80 people, 20 of whom were having their brain activity recorded with EEG. They then compared those EEG measurements to those in two other conditions: one, in which 20 audience members were watching a recording of the first concert on a large movie screen with audio identical to the live concert; and another in which 20 participants in small groups of 2 were seated apart while they observed the recorded musical performance. "Thus, we manipulated the presence of the performers while keeping audience context fixed," the authors explain.
They found that audience members' brain waves were more synchronized with each other when the performers were present. Moreover, individuals whose brain rhythms were more synched up with other audience members enjoyed the concert more and felt more connected to the performers.
"I was extremely excited to see that across the live audience, brain rhythms were synchronized in exactly the frequency range that corresponds to the 'beat' of the music, so it looks as if the beat is driving audience brain rhythms," Henry says. "That may seem common sense, but it's really something. These are novel findings in the context of live music listening that are providing insights into the more social side of music listening."
Music for the future
Moving forward, Henry says that the biggest challenge for studying musical rhythm is that "there's so much other stuff tied up in the experience of music and rhythm listening or performing. Music makes us want to move, it elicits emotions, it triggers memories." Teasing apart these influences will require creative stimulus and experimental design combined with integration of converging evidence across lots of different studies.
In the meantime, Grahn says: "We are seeing relationships between rhythm and language abilities, attention, development, hearing acuity, and even social interactions. Every sensation we have or action we make on the world unfolds over time, and we are now beginning to understand why humans are sensitive to certain types of patterns in time, but not others." Understanding these patterns will inform not only basic science, she says, but also potential music-driven therapies for patients suffering from neurodegenerative diseases.
https://www.sciencedaily.com/releases/2018/03/180327102835.htm
Known risk factors largely explain links between loneliness and first time heart disease/stroke
But social isolation still associated with death among those with preexisting cardiovascular disease
March 26, 2018
Science Daily/BMJ
Conventional risk factors largely explain the links observed between loneliness/social isolation and first time heart disease/stroke, a new study finds. But having few social contacts still remains an independent risk factor for death among those with pre-existing cardiovascular disease.
Recent research has increasingly highlighted links between loneliness and social isolation and cardiovascular disease and death. But most of these studies have not considered a wide range of other potentially influential factors, say the authors.
In a bid to clarify what role these other factors might have, they drew on data from nearly 480,000 people aged between 40 and 69, who were all part of the UK Biobank study between 2007 and 2010.
Participants provided detailed information on their ethnic background, educational attainment, household income, lifestyle (smoking, drinking, exercise) and depressive symptoms.
They were also asked a series of questions to gauge their levels of social isolation and loneliness. Height, weight, and grip strength were measured, and blood samples taken.
Their health was then tracked for an average of 7 years.
Nearly one in 10 (9%) respondents were deemed to be socially isolated, 6 percent lonely, and 1 percent both.
Those who were socially isolated and/or lonely were more likely to have other underlying long term conditions and to be smokers, while those who were lonely reported more depressive symptoms.
During the 7 year monitoring period, 12,478 people died. And 5731 people had a first time heart attack while 3471 had a first time stroke.
Social isolation was associated with a 43 percent higher risk of first time heart attack, when age, sex, and ethnicity were factored in.
But when behavioural, psychological, health, and socioeconomic factors were added into the mix, these factors accounted for most (84%) of the increased risk, and the initial association was no longer significant.
Similarly, social isolation was initially associated with a 39 percent heightened risk of a first time stroke, but the other conventional risk factors accounted for 83 percent of this risk.
Similar results were observed for loneliness and risk of first time heart attack or stroke.
But this was not the case for those with pre-existing cardiovascular disease among whom social isolation was initially associated with a 50 percent heightened risk of death. Although this halved when all the other known factors were considered, it was still 25 percent higher.
Similarly, social isolation was associated with a 32 percent heightened risk of death even after all the other conventional factors had been accounted for.
This is an observational study so no firm conclusions can be drawn about cause and effect, but the findings echo those of other research in the field, say the study authors.
And the size and representative nature of the study prompt the authors to conclude that their findings "indicate that social isolation, similarly to other risk factors such as depression, can be regarded as a risk factor for poor prognosis of individuals with cardiovascular disease."
This is important, they emphasise, as around a quarter of all strokes are recurrent, and targeting treatment of conventional risk factors among the lonely and isolated might help stave off further heart attacks and strokes, they suggest.
https://www.sciencedaily.com/releases/2018/03/180326213304.htm
Coffee affects cannabis and steroid systems
March 15, 2018
Science Daily/Northwestern University
Coffee affects your metabolism in dozens of other ways besides waking you up, including your metabolism of neurotransmitters typically linked to cannabis, a study reports. The neurotransmitters related to the endocannabinoid system -- the same ones affected by cannabis -- decreased after drinking four to eight cups of coffee in a day. That's the opposite of what occurs after someone uses cannabis. The study also gives possible insight in the cause of munchies. Coffee may also increase the elimination of steroids.
It's well known that a morning cup of joe jolts you awake. But scientists have discovered coffee affects your metabolism in dozens of other ways, including your metabolism of steroids and the neurotransmitters typically linked to cannabis, reports a new study from Northwestern Medicine.
In a study of coffee consumption, Northwestern scientists were surprised to discover coffee changed many more metabolites in the blood than previously known. Metabolites are chemicals in the blood that change after we eat and drink or for a variety of other reasons.
The neurotransmitters related to the endocannabinoid system -- the same ones affected by cannabis -- decreased after drinking four to eight cups of coffee in a day. That's the opposite of what occurs after someone uses cannabis. Neurotransmitters are the chemicals that deliver messages between nerve cells.
Cannabinoids are the chemicals that give the cannabis plant its medical and recreational properties. The body also naturally produces endocannabinoids, which mimic cannabinoid activity.
In addition, certain metabolites related to the androsteroid system increased after drinking four to eight cups of coffee in a day, which suggests coffee might facilitate the excretion or elimination of steroids. Because the steroid pathway is a focus for certain diseases including cancers, coffee may have an effect on these diseases as well.
"These are entirely new pathways by which coffee might affect health," said lead author Marilyn Cornelis, assistant professor of preventive medicine at Northwestern University Feinberg School of Medicine. "Now we want to delve deeper and study how these changes affect the body."
Little is known about how coffee directly impacts health. In the new study, Northwestern scientists applied advanced technology that enabled them to measure hundreds of metabolites in human blood samples from a coffee trial for the first time. The study generates new hypotheses about coffee's link to health and new directions for coffee research.
The paper will be published March 15 in the Journal of Internal Medicine.
Drinking lots of coffee for science
In the three-month trial based in Finland, 47 people abstained from coffee for one month, consumed four cups a day for the second month and eight cups a day for the third month. Cornelis and colleagues used advanced profiling techniques to examine more than 800 metabolites in the blood collected after each stage of the study.
Blood metabolites of the endocannabinoid system decreased with coffee consumption, particularly with eight cups per day, the study found.
The endocannabinoid metabolic pathway is an important regulator of our stress response, Cornelis said, and some endocannabinoids decrease in the presence of chronic stress.
"The increased coffee consumption over the two-month span of the trial may have created enough stress to trigger a decrease in metabolites in this system," she said. "It could be our bodies' adaptation to try to get stress levels back to equilibrium."
The endocannabinoid system also regulates a wide range of functions: cognition, blood pressure, immunity, addiction, sleep, appetite, energy and glucose metabolism.
"The endocannabinoid pathways might impact eating behaviors," suggested Cornelis, "the classic case being the link between cannabis use and the munchies."
Coffee also has been linked to aiding weight management and reducing risk of type 2 diabetes.
"This is often thought to be due to caffeine's ability to boost fat metabolism or the glucose-regulating effects of polyphenols (plant-derived chemicals)," Cornelis said. "Our new findings linking coffee to endocannabinoids offer alternative explanations worthy of further study."
It's not known if caffeine or other substances in coffee trigger the change in metabolites.
https://www.sciencedaily.com/releases/2018/03/180315091253.htm
Can't sleep? Could be down to genetics
Large study confirms that insomnia is hereditary
March 9, 2018
Science Daily/Springer
Researchers have identified specific genes that may trigger the development of sleep problems, and have also demonstrated a genetic link between insomnia and psychiatric disorders such as depression, or physical conditions such as type 2 diabetes.
Up to 20 percent of Americans and up to 50 percent of US military veterans are said to have trouble sleeping. The effects insomnia has on a person's health can be debilitating and place a strain on the healthcare system. Chronic insomnia goes hand in hand with various long-term health issues such as heart disease and type 2 diabetes, as well as mental illness such as post-traumatic stress disorder (PTSD) and suicide.
Twin studies have in the past shown that various sleep-related traits, including insomnia, are heritable. Based on these findings, researchers have started to look into the specific gene variants involved. Stein says such studies are important, given the vast range of reasons why people suffer from insomnia, and the different symptoms and varieties of sleeplessness that can be experienced.
"A better understanding of the molecular bases for insomnia will be critical for the development of new treatments," he adds.
In this study, Stein's research team conducted genome-wide association studies (GWAS). DNA samples obtained from more than 33,000 soldiers participating in the Army Study To Assess Risk and Resilience in Servicemembers (STARRS) were analyzed. Data from soldiers of European, African and Latino descent were grouped separately as part of efforts to identify the influence of specific ancestral lineages. Stein and his colleagues also compared their results with those of two recent studies that used data from the UK Biobank.
Overall, the study confirms that insomnia has a partially heritable basis. The researchers also found a strong genetic link between insomnia and type 2 diabetes. Among participants of European descent, there was additionally a genetic tie between sleeplessness and major depression.
"The genetic correlation between insomnia disorder and other psychiatric disorders, such as major depression, and physical disorders such as type 2 diabetes suggests a shared genetic diathesis for these commonly co-occurring phenotypes," says Stein, who adds that the findings strengthen similar conclusions from prior twin and genome-wide association studies.
Insomnia was linked to the occurrence of specific variants on chromosome 7. In people of European descent, there were also differences on chromosome 9. The variant on chromosome 7, for instance, is close to AUTS2, a gene that has been linked to alcohol consumption, as well as others that relate to brain development and sleep-related electric signaling.
"Several of these variants rest comfortably among locations and pathways already known to be related to sleep and circadian rhythms," Stein elaborates. "Such insomnia associated loci may contribute to the genetic risk underlying a range of health conditions including psychiatric disorders and metabolic disease."
https://www.sciencedaily.com/releases/2018/03/180309095520.htm
Is your stress changing my brain?
Stress isn't just contagious; it alters the brain on a cellular level
March 8, 2018
Science Daily/University of Calgary
Scientists have discovered that stress transmitted from others can change the brain in the same way as a real stress does.
In a new study in Nature Neuroscience, Jaideep Bains, PhD, and his team at the Cumming School of Medicine's Hotchkiss Brain Institute (HBI), at the University of Calgary have discovered that stress transmitted from others can change the brain in the same way as a real stress does. The study, in mice, also shows that the effects of stress on the brain are reversed in female mice following a social interaction. This was not true for male mice.
"Brain changes associated with stress underpin many mental illnesses including PTSD, anxiety disorders and depression," says Bains, professor in the Department of Physiology and Pharmacology and member of the HBI. "Recent studies indicate that stress and emotions can be 'contagious'. Whether this has lasting consequences for the brain is not known."
The Bains research team studied the effects of stress in pairs of male or female mice. They removed one mouse from each pair and exposed it to a mild stress before returning it to its partner. They then examined the responses of a specific population of cells, specifically CRH neurons which control the brain's response to stress, in each mouse, which revealed that networks in the brains of both the stressed mouse and naïve partner were altered in the same way.
The study's lead author, Toni-Lee Sterley, a postdoctoral associate in Bains' lab said, "What was remarkable was that CRH neurons from the partners, who were not themselves exposed to an actual stress, showed changes that were identical to those we measured in the stressed mice."
Next, the team used optogenetic approaches to engineer these neurons so that they could either turn them on or off with light. When the team silenced these neurons during stress, they prevented changes in the brain that would normally take place after stress. When they silenced the neurons in the partner during its interaction with a stressed individual, the stress did not transfer to the partner. Remarkably, when they activated these neurons using light in one mouse, even in the absence of stress, the brain of the mouse receiving light and that of the partner were changed just as they would be after a real stress.
The team discovered that the activation of these CRH neurons causes the release of a chemical signal, an 'alarm pheromone', from the mouse that alerts the partner. The partner who detects the signal can in turn alert additional members of the group. This propagation of stress signals reveals a key mechanism for transmission of information that may be critical in the formation of social networks in various species.
Another advantage of social networks is their ability to buffer the effects of adverse events. The Bains team also found evidence for buffering of stress, but this was selective. They noticed that in females the residual effects of stress on CRH neurons were cut almost in half following time with unstressed partners. The same was not true for males.
Bains suggests that these findings may also be present in humans. "We readily communicate our stress to others, sometimes without even knowing it. There is even evidence that some symptoms of stress can persist in family and loved ones of individuals who suffer from PTSD. On the flip side, the ability to sense another's emotional state is a key part of creating and building social bonds."
This research from the Bains lab indicates that stress and social interactions are intricately linked. The consequences of these interactions can be long-lasting and may influence behaviours at a later time.
https://www.sciencedaily.com/releases/2018/03/180308143212.htm
Heart attack patients prescribed antidepressants have worse one-year survival
March 3, 2018
Science Daily/European Society of Cardiology (ESC)
Heart attack patients prescribed antidepressants have lower one-year survival rates, according to new research.
The observational study of nearly 9,000 patients found that those prescribed antidepressants at discharge from hospital after a heart attack had a 66% greater risk of mortality one year later than patients not prescribed the drugs, although they noted the cause is not necessarily related directly to the antidepressants.
Lead author Ms Nadia Fehr, a medical student at the University of Zurich, Switzerland, said: "Previous studies have suggested that cardiovascular disease may increase the likelihood of being depressed. On the other hand, depression appears to increase the probability of developing cardiovascular risk factors. However, little is known about the impact of depression on outcome after a heart attack."
This study assessed the association of antidepressant prescription at hospital discharge with the one-year outcomes of patients with acute myocardial infarction (heart attack).
Data from AMIS Plus, the Swiss nationwide registry for acute myocardial infarction, were used to analyse 8,911 heart attack patients admitted to hospitals in Switzerland between March 2005 and August 2016. Patients were followed up by telephone 12 months after discharge.
The researchers compared patients who received antidepressant medication at discharge with those who did not with regard to baseline characteristics and one-year outcomes including mortality, a subsequent heart attack, and stroke.
A total of 565 (6.3%) patients received antidepressants at discharge from hospital. Compared to those who did not receive the drugs, patients prescribed antidepressants were predominantly female, older, and more likely to have hypertension, diabetes, dyslipidaemia, obesity and comorbidities. They were less likely to undergo percutaneous coronary intervention or receive P2Y12 blockers or statins, and stayed in hospital longer.
After adjusting for baseline characteristics the researchers found that the rates of stroke and subsequent heart attacks were similar between the two groups, but patients prescribed antidepressants had significantly worse survival. The rate of all-cause mortality at one-year after discharge was 7.4% in patients prescribed antidepressants compared to 3.4% for those not prescribed antidepressants (p<0.001).
Antidepressant prescription was an independent predictor for mortality, and increased the odds by 66% (odds ratio: 1.66; 95% confidence interval: 1.16 to 2.39).
"This was an observational study so we cannot conclude that antidepressants caused the higher death rate," noted Ms Fehr.
She concluded: "Our study showed that many patients are treated with antidepressants after a heart attack. More research is needed to pinpoint the causes and underlying pathological mechanisms for the higher mortality we observed in this patient group."
https://www.sciencedaily.com/releases/2018/03/180303095445.htm
Holding hands can sync brainwaves, ease pain
March 1, 2018
Science Daily/University of Colorado at Boulder
A new study by a pain researcher shows that when a romantic partner holds hands with a partner in pain, their brain waves sync and her pain subsides.
Reach for the hand of a loved one in pain and not only will your breathing and heart rate synchronize with theirs, your brain wave patterns will couple up too, according to a study published this week in the Proceedings of the National Academy of Sciences (PNAS).
The study, by researchers with the University of Colorado Boulder and University of Haifa, also found that the more empathy a comforting partner feels for a partner in pain, the more their brainwaves fall into sync. And the more those brain waves sync, the more the pain goes away.
"We have developed a lot of ways to communicate in the modern world and we have fewer physical interactions," said lead author Pavel Goldstein, a postdoctoral pain researcher in the Cognitive and Affective Neuroscience Lab at CU Boulder. "This paper illustrates the power and importance of human touch."
The study is the latest in a growing body of research exploring a phenomenon known as "interpersonal synchronization," in which people physiologically mirror the people they are with. It is the first to look at brain wave synchronization in the context of pain, and offers new insight into the role brain-to-brain coupling may play in touch-induced analgesia, or healing touch.
Goldstein came up with the experiment after, during the delivery of his daughter, he discovered that when he held his wife's hand, it eased her pain.
"I wanted to test it out in the lab: Can one really decrease pain with touch, and if so, how?"
He and his colleagues at University of Haifa recruited 22 heterosexual couples, age 23 to 32 who had been together for at least one year and put them through several two-minute scenarios as electroencephalography (EEG) caps measured their brainwave activity. The scenarios included sitting together not touching; sitting together holding hands; and sitting in separate rooms. Then they repeated the scenarios as the woman was subjected to mild heat pain on her arm.
Merely being in each other's presence, with or without touch, was associated with some brain wave synchronicity in the alpha mu band, a wavelength associated with focused attention. If they held hands while she was in pain, the coupling increased the most.
Researchers also found that when she was in pain and he couldn't touch her, the coupling of their brain waves diminished. This matched the findings from a previously published paper from the same experiment which found that heart rate and respiratory synchronization disappeared when the male study participant couldn't hold her hand to ease her pain.
"It appears that pain totally interrupts this interpersonal synchronization between couples and touch brings it back," says Goldstein.
Subsequent tests of the male partner's level of empathy revealed that the more empathetic he was to her pain the more their brain activity synced. The more synchronized their brains, the more her pain subsided.
How exactly could coupling of brain activity with an empathetic partner kill pain?
More studies are needed to find out, stressed Goldstein. But he and his co-authors offer a few possible explanations. Empathetic touch can make a person feel understood, which in turn -- according to previous studies -- could activate pain-killing reward mechanisms in the brain.
"Interpersonal touch may blur the borders between self and other," the researchers wrote.
The study did not explore whether the same effect would occur with same-sex couples, or what happens in other kinds of relationships. The takeaway for now, Pavel said: Don't underestimate the power of a hand-hold.
"You may express empathy for a partner's pain, but without touch it may not be fully communicated," he said.
https://www.sciencedaily.com/releases/2018/03/180301094822.htm