Women with prolonged mental health problems up to three years after childbirth may be suffering from irregular immune system responses, suggests new research published in the American Journal of Reproductive Immunology.
“We found that women who had clinically elevated symptoms of depression, anxiety, and/or post-traumatic stress disorder (PTSD) two to three years after delivery had genetic evidence of a higher prevalence of immune system defence mechanism activation,” said Eynav Accortt, PhD, principal investigator of the study and director of the Reproductive Psychology Program at Cedars-Sinai.
“These women also appeared to have a reduction in the activity of genes related to antiviral immune responses that can offer the body protection from pathogens,” said Accortt, a clinical psychologist.
Roughly 1 in 8 women experience significant symptoms of perinatal mood and anxiety disorders that can interfere with health and quality of life. Much of the research into maternal mental health to date has focused on the perinatal period and the first year after childbirth.
Cedars-Sinai investigators surveyed 33 women about their mental health over a longer period, two to three years after giving birth. Study participants also provided a blood sample, and scientists performed bioinformatic analyses of differential gene expression.
“Delayed or persistent postpartum anxiety, depression and PTSD is an area that is woefully understudied,” said study co-author Sarah Kilpatrick, MD, PhD, chair of the Department of Obstetrics and Gynecology at Cedars-Sinai.
“In this preliminary research, we have identified genetic differences related to inflammation when comparing women experiencing prolonged symptoms of mood and anxiety disorders to those who did not report poor mental health. Additional studies will be needed for a deeper dive into the role inflammation may play in postpartum mental illness,” said Kilpatrick.
One of the research aims is to design a blood test to identify those at high risk for serious and prolonged postpartum mood disorders, according to Accortt.
“A blood test could help us develop early interventions that provide medical and mental health treatments and support. We want to figure out why some women are at greater risk for depression, anxiety and PTSD. No one should have to suffer for years after childbirth,” said Accortt.
Drugs that block the cancer-promoting activity of oestrogen are known to reduce the risk of developing new breast cancers. A new computer modelling study in the Journal of Clinical Oncology has shown that these treatments could also reduce the risk of dying from the disease in women who are at high risk.
“Recent studies have shown that women diagnosed with oestrogen receptor (ER) positive tumours continue to experience breast cancer recurrence and death for as long as 30 years after their primary diagnosis,” says Claudine Issacs, MD, of the Georgetown Lombardi Comprehensive Cancer Center, one of the study’s two senior authors.
She says this new evidence prompted researchers to revisit the lifetime benefits and harms of risk-reducing medications developed for the primary prevention of breast cancer to see if the drugs could reduce the rate of death from the disease in the long term.
“Based on the available data, recommendations for preventing ER-positive breast cancer with tamoxifen or aromatase inhibitors presumed that women at elevated risk who took the drugs simply reduced their chances of developing the disease, but our modelling study found that, over the long run, there could also be a significant impact on mortality” Isaacs says. “Giving an oestrogen blocker to a woman in her 30s who is at high risk could potentially forestall death due to breast cancer for 20 years or more, which would be significant.”
Over the past several decades, a number of large, federally-funded randomised clinical trials have shown that risk-reducing antioestrogen medications such as tamoxifen and aromatase inhibitors could decrease the incidence of ER-positive breast cancer by 30 to 50% in women who are at high-risk of developing the disease. Despite evidence from these trials, the drugs have remained underutilised, perhaps due to the risk, albeit low, of endometrial cancer conferred by the drugs as well as other factors.
“What has been missing from our conversation until now is our ability to say to women that these drugs can not only prevent them from getting breast cancer but they can ultimately prevent them from dying of the disease,” Isaacs says.
Studies have shown that chemoprevention drugs are most effective if taken for five years and not longer. This latest study shows that the impact on mortality could confer a lasting benefit for a decade or more.
The study used computer models developed by the Cancer Intervention and Surveillance Modeling Network (CISNET), a National Cancer Institute sponsored consortium, to determine the lifetime benefits and harms of oestrogen blockers for women with a five-year risk of developing breast cancer equal to or greater than three percent. The researchers evaluated the effects of oestrogen blockers, along with annual screening with mammograms and MRI if necessary, to calculate the risk of invasive breast cancer, breast cancer death, side-effects, false positives and chances of overdiagnosis.
Tamoxifen, and the use of annual screening, reduced the risk of developing new invasive breast cancers by 40% and reduced the risk of breast cancer deaths by 57%. This translates to 95 fewer invasive breast cancers and 42 fewer breast cancer deaths per 1000 women compared to women who didn’t get screening or risk-reducing drugs. Tamoxifen was not without downsides, potentially increasing new endometrial cancers by up to 11 per 1000. Furthermore, a randomised clinical trial would be too large and take too long to generate results, Isaacs noted.
Both health minister Dr Joe Phaahla and health authorities in the Free State last week denied claims from activists that there are shortages of antiretroviral medicines at health facilities in the province. Authorities did however confirm that some people living with HIV are only given a two-week supply of medicines at a time.
“I can confidently say that there are no stockouts or shortages of ARVs in the Free State,” Phaahla told Spotlight at the World AIDS Day commemoration event in Mangaung.
This was reiterated by spokesperson for the Free State Department of Health, Mondli Mvambi saying, “We do not have shortages of HIV medicines in the province.”
He says allegations of patients not receiving their medication are very serious and cannot be taken lightly. He says should the department hear from patients who are not receiving their HIV medicine, they will investigate.
But Makhosazana Mkhatshwa, a research officer at the Treatment Action Campaign (TAC), says in the past three months, nine clinics in the province indicated that patients have left their facility without the medicine that they needed and of these nine clinics, three of them had sent people home because there was a stockout of HIV medication. She says impacted clinics include Poly Clinic and MUCPP in Mangaung, and Namahadi Clinic in Thabo Mofutsanyana District.
According to community-led monitoring group Ritshidze’s latest report on clinic services in the Free State, there were 40 patient reports this year of shortages of HIV medication compared to 13 patient reports last year. The report states that the most commonly reported medicine shortages by public healthcare users were contraceptives, HIV, and TB medicines. The report was based on monitoring at 28 clinics. TAC is a Ritshidze partner organisation.
Only 7 or 14-day supply for some
One woman Spotlight spoke to at the World AIDS Day commemoration event held in Mangaung last week says she is a patient at Pule Sefatsa Clinic in Botshabelo, Mangaung. “I am forced to go to clinic every week because they only give me a supply for eight days. This is an inconvenience for me because I have to skip work every week just to get my medication.”
Another public healthcare user from Bloemfontein tells Spotlight that for two weeks in October he was stranded without ARVs. He says that he is usually given a 14-day supply at a time. When he requested a full month’s supply to last him through a work-related trip to Cape Town he says his request was declined at the Poly Clinic at Pelenomi Hospital. He says he ended up going without medication.
Aron Malete, District Health Manager for Mangaung, told Spotlight there are no ARV shortages in the district, but asked for details of the above cases so that he could investigate.
The problem is not stockouts per se, but a shortage of medication, says Sello Mokhalipi, Secretary General of Positive Action Campaign. “You will find that there is a shortage of ARVs for seven days, then the next week it will be available,” he says.
Mokhalipi, like other activists Spotlight spoke to, is opposed to giving people only a seven or 14-day supply of medication at a time. He says people should be given enough for three to six months.
When Spotlight put the concerns and calls for multi-month dispensing to Mvambi he says, “We have identified people who are clinic hoppers who steal medicine. They get three months and thereafter run to another clinic to get another three months’ supply. To curb this practice,” Mvambi says, “we keep people on seven and 14 days’ supply The idea is to give them a few days because they claim to have forgotten their clinic cards.”
According to him, people get three months’ supply when they have their clinic card because clinic staff can verify who they are and what medicine they have been receiving.
Doing ‘exceptionally well’ but there are concerns
According to Phaahla who delivered a speech at the World AIDS Day commemoration event, the province has done “exceptionally well in terms of testing, having already surpassed the 94 percent threshold”. Phaahla said 94 percent of people who are living with HIV in the province know their status, 86 percent of those who know their status are on antiretroviral treatment, and 92 percent of those who are on treatment are virally suppressed.
He, however, singled out some districts such as Xhariep and Lejweleputswa where he says the “number of people with HIV and on treatment fare poorly on the target of being virally suppressed”. “This,” Phaahla says, “is very concerning and we must urgently intervene to create a balance among the targets in order to achieve zero new infections by 2030. This includes ensuring that services are brought closer to the people and that our health facilities are adequately resourced with medicine and related necessities.”
“Results for each of the sub-populations vary with adult females at 95 – 91 – 93, adult males at 93 – 77 – 93, and children at 82 – 65 – 68,” says Mvambi. “To achieve the 95 – 95 -95 targets the Free State must increase the number of adult men on ART by 25 745, adult women on ART by 9 744, and children on ART by 5 138.”
“As you can see,” says Mvambi, “the women are more likely to get tested, be initiated on ART, and have their viral load suppressed than their counterparts.”
According to the Free State Department of Health’s latest annual report for the financial year 2021/2022, the number of patients initiated on ARV treatment dropped from 36 776 in 2019/2020 to 26 364 in 2021/2022. In the report, the department states that it failed to meet its target for retaining adults on ART in care. The ART adult remain-in-care rate in 2019/20 was 68%. In 2020/21, it dropped to 52.8% and picked up in 2020/21 at 67.3%. Among the reasons the department cites are the high number of loss to follow-up of clients and “poor tracing by community healthcare workers due to poor supervision”.
NOTE: An employee of the TAC is quoted in this article. Spotlight is published by SECTION27 and the TAC, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
Public transport is used by more than 10 million commuters in South Africa every day. It’s how people get to work, how they get to the grocery store, how they get their children to school. It’s quite simply a way of life.
For many of these commuters, there is no alternative to minibus taxis. They are an indisputably dominant pillar of the informal public transport system, but they are also notoriously unsafe. The constant threat of an accident is a real concern for commuters, especially those who cannot afford private medical aid.
“We live in a country where 73% of the population doesn’t have access to private medical aid. Couple this with the high number of road accidents in South Africa, and what recourse do the vast majority of commuters have if they are involved in a road accident?” asks Rikus Scheepers, managing director at AcciCare Medical Service Providers.
AcciCare is a medical funding company that assists people who do not have medical aid, to get access to private hospital care when they are involved in a motor vehicle accident. Scheepers started AcciCare in 2017, with the intention of making private medical care accessible to all commuters.
“We started AcciCare in a few hospitals and had limited capital to work with but soon realised the extensive need for this type of service. As a start-up without a long trading history, it became impossible to grow the business to meet the demand. We needed a business partner who shared our vision to supply this essential service throughout the country, and so we approached Standard Bank,” says Scheepers.
“AcciCare is a unique concept not offered in South Africa,” says Jocelyn Hamilton at Standard Bank. “When they approached us for finance we had to apply some out-the-box thinking in order to provide a working capital solution that would enable the business to grow and expand into more provinces in the country.”
In the event a person is injured in a motor vehicle accident, AcciCare will assist treating doctors and hospitals to collect and complete the correct documentation in order for medical costs to be claimed back from the Road Accident Fund (RAF). AcciCare provides financial assistance to these service providers, so they don’t carry the costs while waiting for the RAF to settle accounts.
“We firmly believe that all commuters should have access to private medical care when they need it the most. Through our partnership with Standard Bank we are expanding our footprint and we have exciting initiatives in place for 2023, to educate more people about the reliable private care that is available to them,” says Scheepers. “Together with Standard Bank, AcciCare has saved countless lives and has significantly improved the quality of life of those who have unfortunately been involved in a motor vehicle accident.”
“Our business banking model is centred on partnering with clients to grow their businesses in the communities in which they exist. While we came in as a working capital solution that would see AcciCare achieve their vision, in return we indirectly partnered in improving the long-term quality of life for those unfortunate enough to be in need of medical care at critical times. We hope to continue with this partnership, as they take their business to new heights,” says Hamilton.
Young people with Type 1 diabetes (T1D) who took bromocriptine, a medication used to treat Parkinson’s disease and Type 2 diabetes, had lower blood pressure and less stiff arteries after one month of treatment compared to taking placebo, according to a small study published today in Hypertension.
Hypertension and stiff arteries contribute to the development of heart disease, for which those with T1D are at higher risk. Those diagnosed with T1D as children have even higher risks for heart disease than people diagnosed in adulthood. Therefore, researchers are interested in ways to slow down the onset of vascular disease in children with T1D.
“We know that abnormalities in the large vessels around the heart, the aorta and its primary branches, begin to develop in early childhood in people with Type 1 diabetes,” said lead study author Michal Schäfer, PhD, a researcher and fourth-year medical student at the University of Colorado School of Medicine. “We found that bromocriptine has the potential to slow down the development of those abnormalities and decrease the risk for cardiovascular disease in this population.”
The multidisciplinary team conducted this study to examine the impact of bromocriptine on blood pressure and aortic stiffness compared with a placebo in adolescents with Type 1 diabetes. Bromocriptine is in a class of medications called dopamine receptor agonists. It increases levels of dopamine, a chemical in the brain, which leads to an increase in the body’s responsiveness to insulin, called insulin sensitivity. Bromocriptine has been FDA-approved since 2009 to treat adults with Type 2 diabetes due to its effect on insulin sensitivity.
The study included 34 participants (13 male, 21 female) aged 12 to 21 years who had been diagnosed with Type 1 diabetes for at least a year, and their HbA1c was 12% or less. An HbA1c level of 6.5% or higher indicates diabetes. They were randomly divided into two groups of 17, with one group receiving bromocriptine quick-release therapy and the other receiving a placebo once daily. The study was conducted in two phases. Participants took the first treatment or placebo for 4 weeks in phase 1, then had no treatment for a 4-week “wash-out” period, followed by phase 2 with 4 weeks on the opposite treatment. In this “crossover” design, each participant served as their own control for comparison.
Blood pressure and aortic stiffness were measured at the start of the study and at the end of each phase. Aortic stiffness was determined by assessing the large arteries with cardiovascular magnetic resonance imaging (MRI) and a measurement of the velocity of the blood pressure pulse called pulse wave velocity.
The study found:
Compared to placebo, blood pressure was significantly decreased with bromocriptine. On average, bromocriptine therapy resulted in a systolic blood pressure decrease of 5 mm Hg and a diastolic blood pressure decrease of 2 mm Hg at the end of 4 weeks of treatment.
Aortic stiffness was also reduced with bromocriptine therapy. The improvement in aortic stiffness was most pronounced in the ascending aorta with a lowered pulse wave velocity of about 0.4 meters/second, and an increase in distensibility, or elasticity, of 8%. In the thoraco-abdominal aorta, bromocriptine was associated with a lowered pulse wave velocity of about 0.2 meters/second, with a 5% increase in distensibility.
“A stiff aorta predisposes a patient to other health issues, such as organ dysfunction or atherosclerosis and higher stress or strain on cardiac muscle,” Schäfer said. “We were able to take it a notch further and show, using more sophisticated metrics, that these central large arteries are impaired, and impairment among adolescents and young adults with Type 1 diabetes may be decelerated with this drug.”
The study’s small size is a limitation. However, the researchers note that further research into bromocriptine’s impact on vascular health in a greater number of people with Type 1 diabetes is warranted; they are planning larger trials.
UK and Chinese scientists have demonstrated that laser light therapy is effective in improving short term memory in a study published in Science Advances. The innovative, non-invasive therapy could improve short term, or working memory in people by up to 25%.
The treatment, termed transcranial photobiomodulation (tPBM), is applied to the right prefrontal cortex, an area important for working memory. In their experiment, the team showed how working memory improved among research participants after several minutes of treatment. They were also able to track the changes in brain activity using electroencephalogram (EEG) monitoring during treatment and testing.
Previous studies have shown that laser light treatment will improve working memory in mice, and human studies have shown tPBM treatment can improve accuracy, speed up reaction time and improve high-order functions such as attention and emotion. This is the first study, however, to confirm a link between tPBM and working memory in humans.
Co-author Dongwei Li, a visiting PhD student, said, “People with conditions like ADHD (attention deficit hyperactivity disorder) or other attention-related conditions could benefit from this type of treatment, which is safe, simple and non-invasive, with no side-effects.”
In the study researchers at Beijing Normal University carried out experiments with 90 male and female participants aged between 18 and 25. Participants were treated with laser light to the right prefrontal cortex at wavelengths of 1064 nm, while others were treated at a shorter wavelength, or treatment was delivered to the left prefrontal cortex. Each participant was also treated with a sham, or inactive, tPBM to rule out the placebo effect.
After tPBM treatment over 12 minutes, the participants were asked to remember the orientations or colour of a set of items displayed on a screen. The participants treated with laser light to the right prefrontal cortex at 1064 nm showed clear improvements in memory over those who had received the other treatments. While participants receiving other treatment variations were about to remember between three and four of the test objects, those with the targeted treatment were able to recall between four and five objects.
Data, including from electroencephalogram (EEG) monitoring during the experiment was analysed at the University of Birmingham and showed changes in brain activity that also predicted the improvements in memory performance.
The researchers do not yet know precisely why the treatment results in positive effects on working memory, nor how long the effects will last. Further research is planned to investigate these aspects.
Professor Ole Jensen, also at the Center for Human Brain Health, said, “We need further research to understand exactly why the tPBM is having this positive effect, but it’s possible that the light is stimulating the astrocytes –the powerplants – in the nerve cells within the prefrontal cortex, and this has a positive effect on the cells’ efficiency. We will also be investigating how long the effects might last. Clearly if these experiments are to lead to a clinical intervention, we will need to see long-lasting benefits.”
A widely reported study published in Science that presented evidence for a distributed, ‘stepwise’ origin for Omicron across the African continent has drawn criticism from a number of prominent scientists.
Dr Tulio Oliveira, the director of CERI (Centre for Epidemic Response & innovation) and KRISP (KZN Research Innovation & Sequencing Platform) was one of these scientists expressing their doubts over Twitter.
Dr Oliveira tweeted that, like many other scientists, he was sceptical of the Science paper’s narrative of a stepwise emergence of Omicron in Africa.
“First, the ‘fishing’ of intermediates in Africa should also have been performed in Europe and the USA, which were the regions of the world that introduced the majority of Omicron lineages to Africa -“
He also questioned the accuracy of their results due to possible contamination, and also the strength of their analyses, noting that phylogenetic analyses are weak.
For his fourth point, he says that “the Benin sequences could be recombinants of Delta and Omicron, real recombination, or recombination through contamination of the sequencing process.” He was unable to check for the prevalence of mutations.
He also makes a very simple observation regarding the timing of waves: if Omicron arose first in West Africa, why then did South Africa experience the Omicron wave before them?
The paper was also not presented as a preprint to allow for the research community to give feedback and improved the manuscript, a criticism echoed by biologist and physicist Richard Neher.
“Lastly, the results presented do not reject any of the three hypotheses of Omicron evolution (i.e. unsampled location, immune suppressed individual, animal reservoir).”
Nevertheless, he says that “I have many colleagues and collaborators in this paper and would like to recognize that the allele qPCR system to identify BA.1 is a great tool. Also that their mutation analyses are also good.”
Ketamine, an established anaesthetic and increasingly popular antidepressant, dramatically reorganises activity in the brain, as if a switch had been flipped on its active circuits, according to a new study published in a Nature Neuroscience paper.
Researchers observed greatly altered patterns of neuronal activity in the cerebral cortex of animal models after ketamine administration – normally active neurons were silenced while another set that were normally quiet suddenly sprang to action.
This ketamine-induced activity switch in key brain regions tied to depression may impact our understanding of ketamine’s treatment effects and future research in the field of neuropsychiatry.
“Our surprising results reveal two distinct populations of cortical neurons, one engaged in normal awake brain function, the other linked to the ketamine-induced brain state,” said the co-lead and co-senior author Joseph Cichon, MD, PhD, an assistant professor at the University of Pennsylvania. “It’s possible that this new network induced by ketamine enables dreams, hypnosis, or some type of unconscious state. And if that is determined to be true, this could also signal that it is the place where ketamine’s therapeutic effects take place.”
Anaesthesiologists routinely deliver anesthetic drugs before surgeries to reversibly alter activity in the brain so that it enters its unconscious state. Since its synthesis in the 1960s, ketamine has been a mainstay in anaesthesia practice because of its reliable physiological effects and safety profile. One of ketamine’s signature characteristics is that it maintains some activity states across the surface of the brain (the cortex). This contrasts with most anaesthetics, which work by totally suppressing brain activity. It is these preserved neuronal activities that are thought to be important for ketamine’s antidepressant effects in key brain areas related to depression. But, to date, how ketamine exerts these clinical effects remains mysterious.
In their new study, the researchers analysed mouse behaviours before and after they were administered ketamine, comparing them to control mice who received placebo saline. One key observation was that those given ketamine, within minutes of injection, exhibited behavioural changes consistent with what is seen in humans on the drug, including reduced mobility, impaired responses to sensory stimuli, which are collectively termed “dissociation.”
“We were hoping to pinpoint exactly what parts of the brain circuit ketamine affects when it’s administered so that we might open the door to better study of it and, down the road, more beneficial therapeutic use of it,” said co-lead and co-senior author Alex Proekt, MD, PhD, an associate professor at Penn.
Two-photon microscopy was used to image cortical brain tissue before and after ketamine treatment. By following individual neurons and their activity, they found that ketamine turned on silent cells and turned off previously active neurons.
The neuronal activity observed was traced to ketamine’s ability to block the activity of synaptic receptors called NMDA receptors and ion channels called HCN channels. The researchers found that they could recreate ketamine’s effects without the medications by simply inhibiting these specific receptors and channels in the cortex. The scientists showed that ketamine weakens several sets of inhibitory cortical neurons that normally suppress other neurons. This allowed the normally quiet neurons, the ones usually being suppressed when ketamine wasn’t present, to become active.
The study showed that this dropout in inhibition was necessary for the activity switch in excitatory neurons – the neurons forming communication highways, and the main target of commonly prescribed antidepressant medications. More work will need to be undertaken to determine whether the ketamine-driven effects in excitatory and inhibitory neurons are the ones behind ketamine’s rapid antidepressant effects.
“While our study directly pertains to basic neuroscience, it does point at the greater potential of ketamine as a quick-acting antidepressant, among other applications,” said co-author Max Kelz, MD, PhD. “Further research is needed to fully explore this, but the neuronal switch we found also underlies dissociated, hallucinatory states caused by some psychiatric illnesses.”
In August 2007, a soccer match took place that fans of the club Sevilla FC will not forget: the 22-year-old Antonio Puerta suffered a cardiac arrest and collapsed on the field, passing away in hospital a few days later. It was later discovered that the player was affected from a condition named arrhythmogenic cardiomyopathy.
Arrhythmogenic cardiomyopathy can lead to sudden death, and it particularly affects young athletes. Using genetically modified mice, which develop a similar disease to humans, researchers identified previously unknown mechanisms and potential therapeutic targets. Their results were published in the journal Circulation.
This inherited disease is estimated to occur at 1 in every 5000, with men being more commonly affected than women. “Arrhythmogenic cardiomyopathy leads to arrhythmia with a loss of cardiac muscle cells, deposits of connective tissue and fat within the cardiac muscle. This can cause sudden cardiac death, often during exercise,” says Volker Spindler, anatomist and head of the Cell Adhesion group at the University of Basel’s Department of Biomedicine.
Today, a range of gene mutations are known to trigger the condition. However, even with an early diagnosis there is no cure, only options for the management of symptoms are available. “Patients are advised to avoid any competitive or endurance sports and have to take medications such as beta blockers. Where appropriate, a catheter ablation may be performed or an implantable defibrillator may be used” says the cardiologist Gabriela Kuster, who heads the Myocardial Research group at the Department of Biomedicine. Sometimes the only option is a heart transplant.
Cardiac muscle cells become less ‘sticky’
The starting point for the project was the notion that many of the mutations affect structures known as the desmosomes. These are protein clusters on the surface of cardiac muscle cells that ensure a tight connection between the cells. “You can imagine these clusters to act like a piece of Velcro,” says the physician Dr Camilla Schinner, first author of the study. This led to the theory that the mutations reduce adhesion between the cells, thus weakening the cardiac muscle.
To test this hypothesis, Spindler’s team introduced a mutation similar to that found in patients into the genome of mice. The cardiac function of these animals was then examined by Kuster’s group. The result: the genetically modified animals showed a heart disease with arrhythmia that resembled arrhythmogenic cardiomyopathy in humans. In addition, microscopic and biochemical analysis indeed showed reduced adhesion between the cardiac muscle cells. The researchers also observed the scarring of the cardiac muscle typical for this disease.
Preventing cardiac tissue damage
Their next step was to investigate how diseased cardiac muscle differed from healthy conditions at the molecular level. Mice with the mutation showed an increased amount of a particular protein at the Velcro-like structures of the heart muscle cells. This leads, via a series of events, to connective tissue deposition and scarring of the heart. The addition of a substance which blocks this cascade prevented disease progression – which is why Spindler here sees a potential new treatment approach.
“Nevertheless, there is still a long way to go until an application in humans may be considered,” he points out. “But we now have better options to study the disease in more detail to improve our understanding of the underlying mechanisms.”
Many people struggle with feeling groggy in the morning until they get their first coffee, but those who wake up feeling refreshed each day is not just merely a fluke of genetics. Scientists report in the journal Nature Communications that people can wake up each morning without feeling sluggish by paying attention to three key factors: sleep, exercise and the nutritional composition of their breakfast.
The findings come from a study of 833 participants who, over a two-week period, were given a variety of breakfast meals; wore wristwatches to record their physical activity and sleep quantity, quality, timing and regularity; kept diaries of their food intake; and recorded their alertness levels from the moment they woke up and throughout the day. The study included both fraternal and identical twins to disentangle the influence of genes from environment and behaviour.
The researchers found that the secret to alertness is a three-part prescription requiring substantial exercise the previous day, sleeping longer and later into the morning, and eating a breakfast high in complex carbohydrates, with limited sugar. The researchers also discovered that a healthy controlled blood glucose response after eating breakfast is key to waking up more effectively.
“All of these have a unique and independent effect,” said UC Berkeley postdoctoral fellow Raphael Vallat, first author of the study. “If you sleep longer or later, you’re going to see an increase in your alertness. If you do more physical activity on the day before, you’re going to see an increase. You can see improvements with each and every one of these factors.”
Morning grogginess is more than just an annoyance. It has major societal consequences: Many auto accidents, job injuries and large-scale disasters are caused by people who cannot shake off sleepiness. The Exxon Valdez oil spill in Alaska, the Three Mile Island nuclear meltdown in Pennsylvania and an even worse nuclear accident in Chernobyl, Ukraine, are well-known examples.
“Many of us think that morning sleepiness is a benign annoyance. However, it costs developed nations billions of dollars every year through loss of productivity, increased health care utilisation, work absenteeism. More impactful, however, is that it costs lives – it is deadly,” said senior author Matthew Walker, UC Berkeley professor of neuroscience and psychology. “From car crashes to work-related accidents, the cost of sleepiness is deadly. As scientists, we must understand how to help society wake up better and help reduce the mortal cost to society’s current struggle to wake up effectively each day.”
Personalised approach to eating
Walker and Vallat teamed up with researchers in the UK, the US and Sweden to analyse data acquired by a UK company, Zoe Ltd., that has followed hundreds of people for two-week periods in order to learn how to predict individualised metabolic responses to foods based on a person’s biological characteristics, lifestyle factors and the foods’ nutritional composition.
The participants were given pre-prepared meals, with different amounts of nutrients incorporated into muffins, for the entire two weeks to see how they responded to different diets upon waking. A standardised breakfast, with moderate amounts of fat and carbohydrates, was compared to a high protein (muffins plus a milkshake), high carbohydrate or high sugar (glucose drink) breakfast. The subjects also wore continuous glucose monitors to measure blood glucose levels throughout the day.
The worst type of breakfast, on average, contained high amounts of simple sugar; it was associated with an inability to wake up effectively and maintain alertness. When given this sugar-infused breakfast, participants struggled with sleepiness.
In contrast, the high-carbohydrate breakfast was linked to individuals revving up their alertness quickly in the morning and sustaining that alert state.
“A breakfast rich in carbohydrates can increase alertness, so long as your body is healthy and capable of efficiently disposing of the glucose from that meal, preventing a sustained spike in blood sugar that otherwise blunts your brain’s alertness,” Vallat said
“We have known for some time that a diet high in sugar is harmful to sleep, not to mention being toxic for the cells in your brain and body,” Walker added. “However, what we have discovered is that, beyond these harmful effects on sleep, consuming high amounts of sugar in your breakfast, and having a spike in blood sugar following any type of breakfast meal, markedly blunts your brain’s ability to return to waking consciousness following sleep.”
It wasn’t all about food, however. Sleep mattered significantly. In particular, Vallat and Walker discovered that sleeping longer than you usually do, and/or sleeping later than usual, resulted in individuals ramping up their alertness very quickly after awakening from sleep. According to Walker, between seven and nine hours of sleep is ideal for ridding the body of “sleep inertia” – the inability to reach functional cognitive alertness after waking up. Most people need this amount of sleep to remove adenosine, a chemical that accumulates in the body throughout the day and brings on sleepiness in the evening, something known as sleep pressure.
“Considering that the majority of individuals in society are not getting enough sleep during the week, sleeping longer on a given day can help clear some of the adenosine sleepiness debt they are carrying,” Walker speculated.
“In addition, sleeping later can help with alertness for a second reason,” he said. “When you wake up later, you are rising at a higher point on the upswing of your 24-hour circadian rhythm, which ramps up throughout the morning and boosts alertness.”
It’s unclear, however, what physical activity does to improve alertness the following day.
“It is well known that physical activity, in general, improves your alertness and also your mood level, and we did find a high correlation in this study between participants’ mood and their alertness levels,” Vallat said. “Participants that, on average, are happier also feel more alert.”
But Vallat also noted that exercise is generally associated with better sleep and a happier mood.
“It may be that exercise-induced better sleep is part of the reason exercise the day before, by helping sleep that night, leads to superior alertness throughout the next day,” Vallat said.
Walker noted that the restoration of consciousness from non-consciousness — from sleep to wake — is unlikely to be a simple biological process.
“If you pause to think, it is a non-trivial accomplishment to go from being nonconscious, recumbent and immobile to being a thoughtful, conscious, attentive and productive human being, active, awake, and mobile. It’s unlikely that such a radical, fundamental change is simply going to be explained by tweaking one single thing,” he said. “However, we have discovered that there are still some basic, modifiable yet powerful ingredients to the awakening equation that people can focus on — a relatively simple prescription for how best to wake up each day.”
It’s not in your genes
Comparisons of data between pairs of identical and non-identical twins showed that genetics plays only a minor and insignificant role in next-day alertness, explaining only about 25% of the differences across individuals.
“We know there are people who always seem to be bright-eyed and bushy-tailed when they first wake up,” Walker said. “But if you’re not like that, you tend to think, ‘Well, I guess it’s just my genetic fate that I’m slow to wake up. There’s really nothing I can do about it, short of using the stimulant chemical caffeine, which can harm sleep.
“But our new findings offer a different and more optimistic message. How you wake up each day is very much under your own control, based on how you structure your life and your sleep. You don’t need to feel resigned to any fate, throwing your hands up in disappointment because, ‘… it’s my genes, and I can’t change my genes.’ There are some very basic and achievable things you can start doing today, and tonight, to change how you awake each morning, feeling alert and free of that grogginess.”
Walker, Vallat and their colleagues continue their collaboration with the Zoe team, examining novel scientific questions about how sleep, diet and physical exercise change people’s brain and body health, steering them away from disease and sickness.
