Excessive screen time among adolescents negatively impacts multiple aspects of sleep, which in turn increases the risk of depressive symptoms – particularly among girls. That is the conclusion of a new study published in the open-access journal PLOS Global Public Healthby Sebastian Hökby of Karolinska Institutet, Sweden, and colleagues.
Recently, the Swedish Public Health Agency published recommendations that adolescents use no more than two-to-three hours of daily leisure screen time, partly to promote better sleep. Previous studies have suggested associations between screen time, sleep disruptions, and depression in teens. However, sleep problems and depression often coincide, and the direction of these associations has been unclear.
In the new study, researchers tracked 4,810 Swedish students aged 12-16, collecting data on sleep quality and quantity, depressive symptoms, and screen usage at three timepoints over the course of a year.
The researchers found that increased screen time led to deteriorated sleep within three months, impacting both the duration and quality of sleep. Screen time was also found to postpone sleep times towards later hours – disrupting multiple aspects of the human sleep-wake cycle at once. Among boys, screen time had a direct adverse effect on depression after twelve months, while among girls the depressive effect was mediated through sleep disturbances. Sleep could explain about half (38%-57%) of the association between screen time and depression in girls. Boys who spent more time on screens also experienced sleep disruptions, but these were not strongly associated to later depression.
The authors summarize: “In this study, we found that adolescents who reported longer screen times also developed poorer sleep habits over time. In turn, this led to increased depression levels, especially among girls.”
They add: “Our results do suggest that less[…] screen time seems healthier, in line with previous World Health Organization statements…if screen times were somehow reduced, for example through public health policies, our results imply that the high burden of depressive states among young Swedish women, and maybe young men, would likely decrease.”
Mass General Brigham investigators have linked difficult early life experiences with reduced quality and quantity of the white matter communication highways throughout the adolescent brain. This reduced connectivity is also associated with lower performance on cognitive tasks. However, certain social resiliency factors like neighbourhood cohesion and positive parenting may have a protective effect. Results are published in Proceedings of the National Academy of Sciences (PNAS).
White matter are the communication highways that allow the brain networks to carry out the necessary functions for cognition and behaviour. They develop over the course of childhood, and childhood experiences may drive individual differences in how white matter matures. Lead author Sofia Carozza, PhD, and senior author Amar Dhand, MD, PhD, of the Department of Neurology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, wanted to understand what role this process plays in cognition once children reach adolescence.
“The aspects of white matter that show a relationship with our early life environment are much more pervasive throughout the brain than we’d thought. Instead of being just one or two tracts that are important for cognition, the whole brain is related to the adversities that someone might experience early in life,” said Carozza.
The team studied data from 9082 children (about half of them girls, with an average age of 9.5) collected in the Adolescent Brain Cognitive Development (ABCD) study. This study, funded by the National Institutes of Health and conducted at 21 centres across the U.S., gathered information on brain activity and structure, cognitive abilities, environment, mood and mental health. The researchers looked at several categories of early environmental factors, including prenatal risk factors, interpersonal adversity, household economic deprivation, neighbourhood adversity, and social resiliency factors.
Carozza and Dhand used diffusion imaging scanning of the brain to measure fractional anisotropy (FA)—a way of estimating the integrity of the white matter connections—and streamline count, an estimate of their strength. They then used a computational model to compare how these features of white matter were related to both childhood environmental factors and current cognitive abilities such as language skills and mental arithmetic.
Their analysis revealed widespread differences in white matter connections throughout the brain depending on the children’s early-life environments. In particular, the researchers found lower quality of white matter connections in parts of the brain tied to mental arithmetic and receptive language. These white matter differences accounted for some of the relationship between adverse life experiences in early childhood and lower cognitive performance in adolescence.
“We are all embedded in an environment, and features of that environment such as our relationships, home life, neighbourhood, or material circumstances can shape how our brains and bodies grow, which in turn affects what we can do with them,” said Carozza. “We should work to make sure that more people can have those stable, healthy home lives that the brain expects, especially in childhood.”
The researchers note that their study is based on observational data, which means they cannot draw strong causal conclusions. Brain imaging was also only available at a single timepoint, offering a snapshot but not allowing researchers to track changes over time. Prospective studies—following children over time and collecting brain imaging information at multiple time points—would be needed to more definitively connect adversity and cognitive performance.
Neuroblastoma is a rare disease that affects children, often before the age of two. Some are born with the disease. Paediatric surgeon Jakob Stenman is investigating whether targeted radioactive drugs can slow down the disease in those with the most severe form.
Neuroblastoma is a complicated disease, with the most aggressive variant called high-risk neuroblastoma. Children with this disease are treated very intensively. They may undergo surgery, chemotherapy, high-dose chemotherapy with stem cell transplantation, radiotherapy and antibody treatment. Treatment often lasts up to a year and a half.
Despite this, the survival rate is around 60%, according to the Swedish Childhood Cancer Foundation.
“Some relapse in their disease, and we currently lack curative treatment for them,” says Jakob Stenman, a researcher at the Department of Women’s and Children’s Health at Karolinska Institutet.
It is these children, those who have relapsed, that he is treating in a study with targeted radioactive drugs. These are molecules that attach to the surface of cancer cells. These molecules have an appendage: the radioactive substance lutetium-177. The drug first moves through the bloodstream but then attaches to the cancer cells. The emitted radiation damages the cancer cells but unfortunately also the neighbouring healthy cells.
“We have treated ten children so far. Unfortunately, the disease has not disappeared in any of these cases, but it seems to be slowing down, and some benefit more than others from the treatment. When it comes to side effects, the children have tolerated the treatment well,” says Jakob Stenman.
The hope is to be able to prevent relapse
He reports that the interest has been great from clinics in other countries where these children are treated. Hospitals from Lithuania, the Netherlands, the United Kingdom and are now involved.
In neuroblastoma, cancer cells often look very different, even in the same patient. In some metastases, there may be many cells with a surface where the drug attaches, while in other metastases there may be fewer such cells. This means that the targeted drug attaches to fewer cells in some of the metastases. As a result, the local radiation dose is too low in these metastases, which can then continue to grow and spread further.
Jakob Stenman therefore believes that the treatment could be more effective if the radioactive substance used is even more potent, which in this context means that it emits even more energy (ie, radiation). If it then attaches to fewer cells in a metastasis, it might still be able to eliminate all the cancer cells there. But it must act even more locally to protect other tissues from the higher radiation dose.
The researchers have identified several substances they believe could work in this way. These include actinium-225, astatine-211 or lead-212. The effects and side effects of actinium-225 are now being investigated in cell studies and animal experiments. The goal is to start a clinical trial with actinium in three to five years.
“If what we believe turns out to be true, we hope to be able to prevent relapse and thereby enable a cure for a larger proportion of children who have developed high-risk neuroblastoma,” says Jakob Stenman.
Text: Annika Lund for Medicinsk Vetenskap nr 4 2024
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health
Exposure to antibiotics during a key developmental window in infancy can stunt the growth of insulin-producing cells in the pancreas and may boost risk of diabetes later in life, new research in mice suggests. The study, published this month in the journal Science, also pinpoints specific microorganisms that may help those critical cells proliferate in early life.
The findings are the latest to shine a light on the importance of the human infant microbiome—the constellation of bacteria and fungi living on and in us during our first few years. The research could lead to new approaches for addressing a host of metabolic diseases.
“We hope our study provides more awareness for how important the infant microbiome actually is for shaping development,” said first author Jennifer Hill, assistant professor in molecular, cellular and developmental biology at CU’s BioFrontiers Institute. “This work also provides important new evidence that microbe-based approaches could someday be used to not only prevent but also reverse diabetes.”
Something in the environment
More than 2 million U.S. adults live with Type 1 diabetes. The disease typically emerges in childhood, and genetics play a strong role. But scientists have found that, while identical twins share DNA that predisposes them to Type 1 diabetes, only one twin usually gets the disease.
“This tells you that there’s something about their environmental experiences that is changing their susceptibility,” said Hill.
For years, she has looked to microbes for answers.
Previous studies show that children who are breastfed or born vaginally, which can both promote a healthy infant microbiome, are less likely to develop Type 1 diabetes than others. Some research also shows that giving babies antibiotics early can inadvertently kill good bugs with bad and boost diabetes risk.
The lingering questions: What microbes are these infants missing out on?
“Our study identifies a critical window in early life when specific microbes are necessary to promote pancreatic cell development,” said Hill.
A key window of opportunity
She explained that human babies are born with a small amount of pancreatic “beta cells,” the only cells in the body that produce insulin. But some time in a baby’s first year, a once-in-a-lifetime surge in beta cell growth occurs.
“If, for whatever reason, we don’t undergo this event of expansion and proliferation, that can be a cause of diabetes,” Hill said.
She conducted the current study as a postdoctoral researcher at the University of Utah with senior author June Round, a professor of pathology.
They found that when they gave broad-spectrum antibiotics to mice during a specific window (the human equivalent of about 7 to 12 months of life), the mice developed fewer insulin producing cells, higher blood sugar levels, lower insulin levels and generally worse metabolic function in adulthood.
“This, to me, was shocking and a bit scary,” said Round. “It showed how important the microbiota is during this very short early period of development.”
Lessons in baby poop
In other experiments, the scientists gave specific microbes to mice, and found that several they increased their production of beta cells and boosted insulin levels in the blood. The most powerful was a fungus called Candida dubliniensis.
The team used faecal samples from The Environmental Determinants of Diabetes in the Young (TEDDY) study to make what Hill calls “poop slushies” and fed them to the mice.
When the researchers inoculated newborn mice with poop from healthy infants between 7 to 12 months in age, their beta cells began to grow. Poop from infants of other ages did not do the same. Notably, Candida dublineinsis was abundant in human babies only during this time period.
“This suggests that humans also have a narrow window of colonisation by these beta cell promoting microbes,” said Hill.
When male mice that were genetically predisposed to Type 1 diabetes were colonised with the fungus in infancy, they developed diabetes less than 15% of the time. Males that didn’t receive the fungus got diabetes 90% of the time.
Even more promising, when researchers gave the fungus to adult mice whose insulin-producing cells had been killed off, those cells regenerated.
Too early for treatments
Hill stresses that she is not “anti-antibiotics.” But she does imagine a day when doctors could give microbe-based drugs or supplements alongside antibiotics to replace the metabolism-supporting bugs they inadvertently kill.
Poop slushies (faecal microbiota transplants) have already been used experimentally to try to improve metabolic profiles of people with Type 2 diabetes, which can also damage pancreatic beta cells.
But such approaches can come with real risk, since many microbes that are beneficial in childhood can cause harm in adults. Instead, she hopes that scientists can someday harness the specific mechanisms the microbes use to develop novel treatments for healing a damaged pancreas—reversing diabetes.
She recently helped establish a state-of-the-art “germ-free” facility for studying the infant microbiome at CU Boulder. There, animals can be bred and raised entirely without microbes, and by re-introducing them one by one scientists can learn they work.
“Historically we have interpreted germs as something we want to avoid, but we probably have way more beneficial microbes than pathogens,” she said. “By harnessing their power, we can do a lot to benefit human health.”
Seizures in newborns are one of the most frequent acute neurological conditions among infants admitted to neonatal care units. A study published in Developmental Medicine & Child Neurology indicates that newborns experiencing such neonatal seizures face an elevated risk of developing epilepsy.
For the study, investigators analysed data on all children born in Denmark between 1997 and 2018, with the goal of comparing the risk of epilepsy in children with and without neonatal seizures.
Among 1,294,377 children, the researchers identified 1,998 who experienced neonatal seizures. The cumulative risk of epilepsy was 20.4% among children with neonatal seizures compared with 1.15% among children without. This indicates that 1 in 5 newborns with neonatal seizures will develop epilepsy.
Epilepsy was diagnosed before 1 year of age in 11.4% of children with neonatal seizures, in an additional 4.5% between 1 and 5 years, 3.1% between 5 and 10 years, and 1.4% between 10 and 22 years. Stroke, hemorrhage, or structural brain malformations in newborns, as well as low Apgar scores, were associated with the highest risks of developing epilepsy.
“Our study highlights that there are risk factors that may be used to identify infants for tailored follow-up and preventive measures,” said corresponding author Jeanette Tinggaard, MD, PhD, of Copenhagen University Hospital – Rigshospitalet. “Importantly, four out of five neonatal survivors with a history of neonatal seizures did not develop epilepsy, and we suggest future studies to explore a potential genetic predisposition.”
A review in Clinical & Experimental Allergy concludes that exposing young children to small amounts of foods that they’re allergic to is safer than avoiding the foods altogether, which could be very dangerous if accidental exposure occurs.
The review notes that exposing preschool-aged children to small amounts of food allergens—called oral immunotherapy—can lessen the severity of a reaction following an accidental exposure. Also, delaying exposure until a later age misses the window of opportunity when oral immunotherapy is safest, and it prolongs unnecessary dietary restrictions. Also, after early childhood avoidance, some people who outgrow their allergy will not reincorporate the food into their diet due to fear and anxiety, thus potentially increasing their chance of redeveloping the allergy.
A growing body of evidence indicates that oral immunotherapy is safe and effective in preschoolers, but additional research is needed to clarify its impact on children’s health and quality of life.
“This research highlights a critical shift in how we approach food allergies—moving from strict avoidance to controlled exposure in early childhood, which not only reduces the risk of severe reactions but also helps prevent long-term negative consequences of living with food allergies,” said corresponding author Lianne Soller, PhD, of the University of British Columbia, in Canada.
Exposure to high ambient temperatures is associated with lower connectivity in three brain networks in preadolescents, suggesting that heat may impact brain function. This is the conclusion of a study led by the Barcelona Institute for Global Health (ISGlobal). The results have been published in the Journal of the American Academy of Child & Adolescent Psychiatry.
The study involved 2229 children aged 9 to 12 from the “Generation R” cohort in Rotterdam, Netherlands. Functional connectivity data from brain networks, i.e., how different regions of the brain communicate and collaborate, were assessed using resting-state magnetic resonance imaging, when the children were not performing any active tasks. Daily mean temperature estimates were obtained from the UrbClim urban climate model, developed by the Flemish Institute for Technological Research. Temperature values were calculated for the period from 2013 to 2015, assigning daily averages to each participant based on their home address.
Higher ambient temperatures during the week preceding the MRI assessment were associated with lower functional connectivity within the medial parietal, salience, and hippocampal networks, which are essential for proper brain functioning. This implies that brain areas may work less synchronously, affecting processes such as attention, memory, and decision-making. The medial parietal network is related to introspection and self-perception; the salience network detects environmental stimuli and prioritises what deserves our attention; and the hippocampal network is critical for memory and learning.
The research shows that the association between high temperatures and lower functional connectivity was strongest on the day before the brain scan and progressively decreased on subsequent days. In contrast, low average daily temperatures were not associated with functional connectivity.
“We hypothesise that dehydration could explain our findings, as children are particularly vulnerable to fluid loss when exposed to heat, which can affect the functional connectivity of brain networks,” says study lead author Laura Granés, researcher at IDIBELL and ISGlobal.
“In the current climate emergency, public health policies aimed at protecting children and adolescents from high temperatures could help mitigate potential effects on brain function,” says Mònica Guxens, ICREA researcher at ISGlobal and senior author of the study.
Implications for mental health
Although brain function alterations have been suggested as a possible mechanism linking temperature and mental health, no study to date has examined the effects of ambient temperature on functional brain networks. In another recent study, the same research team found that exposure to cold and heat can affect psychiatric symptoms such as anxiety, depression and attention problems. In addition, other studies have linked lower connectivity within the brain’s salience network to suicidal ideation and self-harming behaviours in adolescents with depression, as well as to anxiety disorders.
“Given the role of the salience network in suicidal ideation, our findings raise a new hypothesis: high temperatures could decrease the functional connectivity of this network, indirectly contributing to a higher risk of suicide in individuals with pre-existing mental health conditions,” explains Carles Soriano-Mas, researcher at IDIBELL and the University of Barcelona and one of the study’s authors. “While we do not propose that these connectivity changes, triggered by heat exposure, directly induce suicidal behaviours, they could act as a trigger in vulnerable individuals,” adds the researcher.
Neuroblastoma is a solid tumour that occurs in children. When high-risk, the disease has a poor prognosis. Decades ago, adding the drug retinoic acid to neuroblastoma treatment increased survival by 10–15%. However, this effect was only evident in post-chemotherapy consolidation after bulky primary tumours had largely been eliminated. Why retinoic acid is effective in this setting but not against primary tumours, has been speculated about for nearly 50 years.
St. Jude Children’s Research Hospital scientists resolved the mystery in a new study, showing retinoic acid uses a novel mechanism to kill metastasised neuroblastoma. The drug “hijacks” a normal developmental pathway to trigger cancer cell death. The findings, which have implications for future combination therapy approaches, appears in Nature Communications.
“We’ve come up with an explanation for a decades-long contradiction about why retinoic acid works in post-chemotherapy consolidation but has little impact on primary neuroblastoma tumours,” said senior co-corresponding author Paul Geeleher, PhD. “Retinoic acid’s activity heavily depends on the cellular microenvironment.”
The cellular microenvironment is the soup of chemicals, proteins and other signals that surround a cell, and which is unique to that part of the body. For example, the bone marrow microenvironment contains signals to grow blood cells and restructure bone. Metastasised neuroblastoma cells often migrate to bone marrow, where the bone morphogenetic protein (BMP) pathway signalling is highly active. The researchers showed that BMP signaling makes neuroblastoma cells much more vulnerable to retinoic acid.
“Unexpectedly, we found that cells expressing genes from the BMP signaling pathway were very sensitive to retinoic acid,” said co-first and co-corresponding author Min Pan, PhD, St. Jude Department of Computational Biology. “However, since the bone marrow microenvironment causes neuroblastoma cells there to have higher BMP activity, it neatly explained why retinoic acid is very effective at treating those cells during consolidation therapy, but not the primary tumours during up-front treatment.”
Hijacking development to drive metastatic neuroblastoma cell death
Using gene editing technology, the scientists uncovered the relationship between BMP signaling and retinoic acid. They assembled a group of neuroblastoma cell lines susceptible to retinoic acid, then cut out genes to find which were responsible for the drug’s activity. Genes in the BMP pathway had the largest effect while providing a plausible explanation for retinoic acid’s varying outcomes in patients.
“We found that, in neuroblastoma, BMP signaling works with retinoic acid signaling in the same way as during development,” said co-first author Yinwen Zhang, PhD, who characterised how transcription factors, the proteins that bind DNA to regulate gene expression, led to different results in highly retinoic acid-sensitive or insensitive neuroblastoma cells. “If there are a lot of BMP-signaling pathway transcription factors already on DNA, then retinoic acid signaling combines with it to promote downstream cell death–related gene expression. This occurs both in normal embryonic development and neuroblastoma cells in certain microenvironments.”
“We are the first to uncover such an example of ‘hijacking’ a normal embryonic developmental process preserved in cancer that we can exploit therapeutically,” Geeleher said. “Now, we can look for similar processes in other diseases to design less toxic and more effective treatment strategies.”
Obesity rates are set to skyrocket, with one in six children and adolescents worldwide forecast to be obese by 2050, according to a new study. But with significant increases predicted within the next five years, the researchers stress urgent action now could turn the tide on the public health crisis.
The research, led by Murdoch Children’s Research Institute (MCRI) and published in The Lancet, found a third of children and adolescents will be overweight (385 million) or obese (360 million) within the next 25 years. The forecast equates to 356 million children aged 5–14 years and 390 million aged 15–24 years with one in six facing obesity.
The global obesity rate for those between 5-24 years old tripled from 1990 to 2021, rising by 244 per cent to 174 million, suggesting that current approaches to curbing increases in obesity have failed a generation of young people. As of 2021, 493 million children and adolescents were overweight or obese.
MCRI Dr Jessica Kerr said if immediate five-year action plans were not developed, the future was bleak for our youth.
“Children and adolescents remain a vulnerable population within the obesity epidemic,” she said, adding that obesity drives a whole range of diseases. Prevention is key as obesity rarely resolves after adolescence.
“Despite these findings indicating monumental societal failures and a lack of coordinated global action across the entire developmental window to reduce obesity, our results provide optimism that this trajectory can be avoided if action comes before 2030.”
The United Arab Emirates, Cook Islands, Nauru and Tonga are forecast to have the highest prevalence while China, Egypt, India and the US will have the greatest number of children and adolescents with obesity by 2050.
In Australia, children and adolescents have experienced some of the fastest transitions to obesity in the world. Girls are already more likely to be obese than overweight. Overall, by 2050 for those aged 5-24 years, 2.2 million are forecasted to be obese and 1.6 million overweight.
Globally, there will be more boys, 5–14 years, with obesity than being overweight by 2050.
“Without urgent policy reform, the transition to obesity will be particularly rapid in north Africa, the Middle East, Latin America and in the Caribbean, where the rise is concurrent with high population numbers and limited resources,” Dr Kerr said.
“Many regions have historically had to focus on preventing undernutrition and stunting in children. To prevent a public health emergency from this newer threat, an immediate imperative should be creating national surveillance surveys of obesity in children and adolescents in every country.”
Dr Kerr said older adolescent girls, aged 15-24 years entering their reproductive years, were a priority population for intervention.
“Adolescent girls who are obese are a main focus if we are to avoid intergenerational transmission of obesity, chronic conditions and the dire financial and societal costs across future generations,” she said.
“With this age group increasingly being out of school and cared for by adult services, we need to focus interventions at the community and commercial level.”
Getting at least 30 minutes of daily summer sun in the first year of life may mean a lower relapse risk for children who are diagnosed with multiple sclerosis (MS) later, according to a study published in Neurology® Neuroimmunology & Neuroinflammation, an official journal of the American Academy of Neurology. The study also found if a child’s biological mother had at least 30 minutes of daily sun during the second trimester of pregnancy, the child had a lower risk of MS relapses.
The study does not prove that sun lowers relapse risk for children with MS, it only shows an association. “It is important not to spend too much time in the sun without sun protection, however greater exposure to sun has been tied in previous research to a lower risk of developing MS in childhood,” said Gina Chang, MD, MPH, of The Children’s Hospital of Philadelphia and member of the American Academy of Neurology. “It’s encouraging that our study found that greater sun exposure during early development may also be beneficial in helping to reduce disease activity in children who are later diagnosed with MS.”
For the study, researchers looked at health records from 18 MS clinics across the United States to identify 334 children and young people with childhood-onset MS age four to 21. Participants were within four years of experiencing their first symptoms. The median follow-up time was 3.3 years. To determine sun exposure, participants’ parents or guardians completed questionnaires that asked how much time the participant and their biological mother had spent in the sun at various periods of life, what kind of clothing they typically wore and how often they used sunscreen.
Of the total group, 206, or 62%, experienced at least one relapse during the study. Relapses were defined as new or returning symptoms lasting for at least 24 hours and separated by at least 30 days from the last MS attack, without a fever or infection. They found that of 75 participants who had 30 minutes to an hour of daily summer sun during their first year of life, 34 children, or 45%, had a relapse.
Of the 182 participants who had less than 30 minutes of daily summer sun during their first year of life, 118 children, or 65%, had a relapse. After adjusting for factors such as tobacco exposure in the first year of life, season of birth, the type of MS medication taken and use of sun protection such as sunscreen, hats and clothing, researchers found that 30 or more minutes of daily summer sun during the first year of life was associated with a 33% lower risk of relapse compared to less than 30 minutes of daily summer sun.
Researchers also looked at sun exposure for the biological mothers of the children. They found that 30 minutes or more of daily sun during the second trimester of pregnancy was associated with a 32% reduced risk of relapse for their child with MS.
“Our findings suggest that sun exposure in early childhood may have long-lasting benefits on the progression of childhood-onset MS,” said Chang. “Future studies should look at how time in the sun at other time periods before and after MS diagnosis affects disease course, to better guide sun exposure recommendations for children with MS and to help design potential clinical trials.” A limitation of the study was that it relied on participants’ parents or guardians reporting their sun exposure and use of sun protection, which they may not have remembered accurately.
