Hydrothermal vents have been identified as a previously undiscovered source of dissolved black carbon in the oceans, furthering the understanding of the role of oceans as a carbon sink.
The ocean is one of the largest dynamic carbon sinks in the world, and is susceptible to increased carbon emissions from human activities. There are even proposals to use the ocean to sequester carbon in an effort to reduce the carbon emissions. However, much of the processes by which the ocean functions as a carbon sink are not fully understood.
Associate Professor Youhei Yamashita and grad student Yutaro Mori at Hokkaido University, along with Professor Hiroshi Ogawa at AORI, The University of Tokyo, have revealed conclusive evidence that hydrothermal vents are a previously unknown source of dissolved black carbon in the deep ocean. Their discoveries were published in the journal Science Advances.
“One of the largest carbon pools on the Earth’s surface is the dissolved organic carbon in the ocean,” explains Ogawa. “We were interested in a portion of this pool, known as dissolved black carbon (DBC), which cannot be utilized by organisms. The source of DBC in the deep sea was unknown, although hydrothermal vents were suspected to be involved.”
The researchers analyzed the distribution of DBC in the ocean basins of the North Pacific Ocean and Eastern South Pacific Ocean, and compared the data with previously reported concentrations of a helium isotope that is associated with hydrothermal vent emissions, as well as oxygen utilization in these areas.
Their findings showed that hydrothermal vents were an important source of DBC in the Pacific Ocean. This hydrothermal DBC is most likely formed due to the mixing of the hot fluids from hydrothermal vents with cold seawater, and is transported over long distances — up to thousands of kilometers away.
“Most importantly, our research indicates that the DBC from hydrothermal vents is an important source of dissolved organic carbon in the deep ocean. In terms of DBC inputs to the ocean, hydrothermal vents may contribute up to half as much DBC as that which is formed by biomass burning or fossil fuel combustion and subsequently transported via rivers or atmospheric deposition,” concluded Yamashita. Further research is required to understand exactly how DBC is formed from hydrothermal vents.
Researchers have found that the movement of glaciers in Greenland is more complex than previously thought, with deformation in regions of warmer ice containing small amounts of water accounting for motion that had often been assumed to be caused by sliding where the ice meets the bedrock beneath.
The international team of researchers, led by the University of Cambridge, used computer modelling techniques based off earlier fibre-optic measurements from the Greenland Ice Sheet to build a more detailed picture of the behaviour of the world’s second-largest ice sheet.
Their results, reported in the journal Science Advances, could be used to develop more accurate predictions of how the Greenland Ice Sheet will continue to move in response to climate change.
Mass loss from the Greenland Ice Sheet has increased sixfold since the 1980s and is now the single largest contributor to global sea-level rise. Around half of this mass loss is from surface meltwater runoff, while the other half is driven by discharge of ice directly into the ocean by fast-flowing glaciers that reach the sea.
The RESPONDER project, funded by the European Research Council, is exploring the dynamics of the Greenland Ice Sheet using a combination of physical measurements and computer modelling.
The current research builds on earlier observations reported by the RESPONDER team in 2021 using fibre-optic cables. In that work, the team found that the temperature of ice sheets does not vary as a smooth gradient, but is far more heterogeneous, with areas of highly localised deformation warming the ice further.
The borehole measurements also showed that the ice at the base contains small amounts — up to roughly two percent — of water. In some parts of the ice sheet, this mixed ice-water layer, called temperate ice, was around eight metres thick, but in other parts it was up to 70 metres thick.
“The addition of even tiny amounts of water softens the ice considerably, transforming it into a unique material with substantially altered mechanical characteristics,” said first author Dr Robert Law, who completed the work while based at Cambridge’s Scott Polar Research Institute and is now based at the University of Bergen. “We wanted to know why the thickness of this layer varied so much, because if we don’t fully understand it, our models of ice sheet behaviour won’t fully capture the physical processes occurring in nature.”
“The textbook view of glacier motion is that it occurs with a neat partitioning of basal sliding and internal deformation, and that both are well understood,” said co-author and RESPONDER project leader Professor Poul Christoffersen, who is based at SPRI. “But that’s not what we observed when we looked carefully in boreholes with new techniques. With less detailed observations in the past, it was difficult to get a really good picture of how the ice sheet moves and even more challenging to replicate it with computer models.”
Law, Christoffersen and their colleagues from the UK, US, Switzerland and France developed a model based on their earlier borehole measurements that can account for all of the new observations.
Importantly, they accounted for natural variations in the landscape at the base of the ice, which, in Greenland, is full of rocky hills, basins and deep fjords. The researchers found that as a glacier moves over a large obstacle or hill, there is a deformation and heating effect which sometimes extends several hundred metres from the ice sheet base. Previously, this effect was omitted in models.
“The stress on the ice base is highest at the tops of these hills, which leads to more basal sliding,” said Law. “But so far most models have not accounted for all of these variations in the landscape.”
By incorporating these variations, the model developed by the researchers showed that a variable layer of temperate ice forms as the glacier moves over the landscape, whether the glacier itself is fast- or slow-moving. The thickness of this temperate ice layer agrees with the earlier borehole measurements, but diverges significantly from standard modelling methods used to predict sea level rise from ice sheets.
“Because of this hilly landscape, the ice can go from sliding across its base almost entirely to hardly sliding at all, over short distances of just a few kilometres,” said Law. “This directly influences the thermal structure — if you’ve got less basal sliding then you’ve got more internal deformation and heating, which can lead to the layer of temperate ice getting thicker, altering the mechanical properties of the ice over a broad area. This temperate basal ice layer can actually act like a deformation bridge between hills, facilitating the fast motion of the much colder ice directly above it.”
The researchers hope to use this improved understanding to build more accurate descriptions of ice motion for the ice sheet models used in predicting future sea level rise.
The research was funded in part by the European Union and the Natural Environment Research Council (NERC), part of UK Research and Innovation (UKRI).
In a study of nearly 3,000 schoolchildren, silver diamine fluoride — a liquid that is brushed onto the surface of teeth to prevent cavities or keep them from worsening — was as effective against cavities as dental sealants, the standard of care. A single dose of either topical treatment given in elementary schools prevented roughly 80% of cavities and kept 50% of cavities from worsening when children were seen two years later.
The findings, published in JAMA Network Open, offer an efficient and cost-effective approach to improving children’s oral health through school-based care.
Dental cavities are the most common chronic disease in children, and kids from low-income families are twice as likely to have cavities as those from higher-income families. Without proper and timely intervention, cavities can lead to severe infections, reduce children’s quality of life, and are associated with lower student academic performance and school attendance. But getting kids to a dentist for the recommended twice-yearly visits can be challenging, especially when parents need to take time off of work.
To reduce the barriers to seeing a dentist, some basic dental services can be offered in schools, especially those serving children from low-income families. For example, the Centers for Disease Control and Prevention recommends and funds school sealant programs. In 2017, NYU College of Dentistry researchers received funding from the Patient-Centered Outcomes Research Institute (PCORI) to run the nation’s largest school-based cavity prevention study, which they named CariedAway.
CariedAway is a randomized trial comparing the effectiveness of two cavity-prevention techniques: a “simple” treatment using silver diamine fluoride (SDF) and fluoride varnish, and a “complex” treatment using traditional glass ionomer sealants and fluoride varnish. Both are non-invasive and applied to the surface of teeth to prevent and arrest cavities in children, but for the same time and cost, providers can treat more children with the simpler SDF therapy.
The study included 2,998 children in kindergarten through third grade at 47 New York City schools. The schools — which serve a racially diverse group of students, most of whom are from low-income families — were randomized to receive either the simple or complex treatment.
Upon visiting each school, the clinical research team — which included a supervising dentist, dental hygienists, registered nurses, and assistants — did baseline exams to measure any tooth decay, and then applied fluoride varnish and either sealants or SDF, depending on whether the school was assigned to receive the complex or simple treatment.
The initial visits took place in 2019 and early 2020, and were paused when the COVID-19 pandemic temporarily closed New York City schools and halted all school-based care. Two years later, schools allowed the clinical research team to resume, and they returned to each school for follow-up visits.
The researchers found that both the simple and complex treatments were successful: just one cavity prevention treatment prevented more than 80% of cavities (81% for SDF and 82% for sealants) and stopped half of cavities from progressing (56% for SDF and 46% for sealants).
“Without prevention, dental cavities grow continuously if not treated. One CariedAway cavity prevention treatment, provided just before schools closed during the pandemic, was remarkably effective over the following two-year period,” said Richard Niederman, DMD, professor in the Department of Epidemiology & Health Promotion at NYU College of Dentistry, co-principal investigator of CariedAway, and the study’s senior author. “I know of no other dental preventive intervention that had this great a beneficial impact across the pandemic.”
While the limited availability of trained dental professionals can pose challenges for school sealant programs, as sealants are applied by a dentist or dental hygienist, SDF may be an attractive alternative, as it can also be applied by nurses — a workforce already in place in many schools.
“Our results support the use of SDF for cavity prevention in school-based oral health programs and offer an opportunity for expanding access to critical oral health care,” said Ryan Richard Ruff, MPH, PhD, associate professor in the Department of Epidemiology & Health Promotion at NYU College of Dentistry, co-principal investigator of CariedAway and the study’s first author.
Tamarinda Barry-Godín, DDS, MPH, was a study co-author. This research was funded by the Patient-Centered Outcomes Research Institute (award PCS-1609-36824).
New adoptive T cell therapies — in which T cells, the immune system’s natural hunters patrolling the body for foreign adversaries, are retrieved from cancer-riddled patients, super-charged and amplified outside the body, and then infused back into the same patient — are changing the prospects of cancer patients. Since 2017, when CAR (chimeric antigen receptor)-T cells were green-lighted as the first modified therapeutic cells by the Federal Drug Administration (FDA) to treat leukemia, five similar products have since been approved and more than 20,000 people have been treated with this game-changing immunotherapy.
CAR-T cells are engineered to carry synthetic membrane-spanning receptor molecules that use their outside-facing portion to bind to antigens on cancer cells, which their inside-facing portion responds to by switching on a powerful tumor cell-destroying program. However, not all patients respond equally well to CAR-T cell therapies, and cancer immunologists have been trying to figure out what makes them work well or fail. Despite a budding understanding of differences between cancer patients’ T cells and healthy individuals’ T cells, these insights have not been taken into account in CAR-T cell manufacturing processes. All processes use a similar type of stimulation with T-cell specific agonists and general immune-stimulating cytokines to create infusible CAR-T cell products, irrespective of variations in the original T cells’ phenotype.
Now, a collaboration between bioengineers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) led by David Mooney, Ph.D. and cancer-immunologists at the Dana-Farber Cancer Institute (DFCI) led by Catherine Wu, M.D., Ph.D. has demonstrated that personalizing CAR-T cell stimulation during manufacturing can significantly enhance the consistency and potency of the resulting CAR-T cell products. By using artificial antigen-presenting cell mimicking scaffolds (APC-ms), the team was able to fine-tune the levels of T cell stimulation to match the phenotype of T cells obtained from leukemia patients, and significantly enhanced their ex vivo and in vivo tumor-clearing abilities. The findings are published in Nature Communications.
“We show that CAR-T cell products made from T cells derived from cancer patients are generally less functional than CAR-T cells products derived from healthy individuals,” said Founding Wyss Core Faculty member Mooney. “Matching the CAR-T cell antigen-stimulation dose to the phenotype of patients’ T cells using a precisely controllable biomaterials approach that closely mimics natural antigen presentation can significantly improve their function. This approach could further personalize CAR-T cell therapy and remove an existing inadequacy from current T cell manufacturing.” Mooney also is Robert P. Pinkas Family Professor of Bioengineering at SEAS, and a lead of the NIH-funded Immunomaterials to Improve Immunotherapy (i3) Center coordinated at the Wyss Institute. This project was conceived at the Center, and Wu is one of its Principal Investigators.
Cutting the keys for personalized CAR-T therapies
The team investigated the phenotypes of T cells that they isolated from samples obtained from patients suffering from acute lymphoblastic leukemia (ALL) and chronic lymphoblastic leukemia (CLL), as well as from healthy donors. Next, they utilized APC-ms to provide the T cells with different doses of anti-CD3/anti-CD28 antigen stimulation and thus created a CAR-T cell library. All CAR-T cell products contained in the library were then probed again for functional differences, including their ability to kill cancer cells in vitro. The researchers directly compared their approach with one that is commonly used in CAR-T cell manufacturing, which presents the same antigens on rigid magnetic beads (Dynabeads) to T cells.
A key finding was that cancer patients’ T cells were much more easily over-stimulated at antigen doses commonly used during CAR-T cell manufacturing than “healthy” T cells. This made them lose their functionality, or become more “exhausted” as immunologists say, and decreased their ability to proliferate. CAR-T cells not only need to be transformed into a functional state but also amplified by millions to be able to eliminate tumor cells and metastasis in the entire body.
“By exploring a precise, narrow range of stimulation doses made possible with APC-ms, we show that there is something like a personalized ‘sweet spot’ for patient-derived T cells that maximizes functionality and amplification, which is, on average, lower than the usual doses,” said first-author David Zhang, who is a graduate student on Mooney’s team. “The APC-ms approach functions much more naturally than Dynabeads, because highly controllable levels of T-cell signals are embedded into a lipid bilayer, which allows the CAR-T cells to push and pull at them as just as T cells usually do across the ‘immunological synapse’ between them and antigen-presenting cells when T cell stimulation is at its best.”
From in vitro studies to cell manufacturing
While the team did not observe any significant differences between CAR-T cells created from ALL and CLL patient samples, overall their approach generated more cells with high cytotoxic potential toward tumor cells, a more balanced ratio between cytotoxic CD8+ T cells and CD4+ T cells that support their function, and more memory T cells that themselves are not cytotoxic but can be activated in later responses. In a mouse in vivo study, infused CAR-T cell products created with different levels of stimulation also exhibited significantly different abilities to control CD19-expressing Burkitt’s lymphoma, with cells again stimulated at lower than usual levels during manufacturing showing the strongest potential.
“We constructed a proof-of-concept model that is based on the quantifiable relationship between the phenotype of a T cell blood sample and its CAR-T cell products, and that outputs an optimal T cell stimulation dose for personalized CAR-T cell production,” said Wu. “Given that T cell samples are always fingerprinted for important markers at the beginning of the cell manufacturing process, similar strategies could be devised to further personalize the therapy using the APC-ms approach.” Wu is the Lavine Family Chair, Preventative Cancer Therapies at DFCI, and Professor of Medicine at Harvard Medical School.
“Dave Mooney’s team in the Wyss’ Immunomaterials platform is pushing the envelope of CAR-T cell and other immunotherapies using entirely new engineering and materials-based approaches. Hopefully, this will eventually enable us to also mobilize the immune system against recalcitrant solid tumors for which no therapies exist yet. It’s also a great example of where less is more,” said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital, and Hansjörg Wyss Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
Additional authors on the study are Wyss and SEAS researchers Kwasi Adu-Berchie, Siddharth Iyer, Yutong Liu, and Joshua Brockman; DFCI researcher Nicoletta Cieri, and Donna Neuberg, Sc.D., a data scientist at the DFCI and member of the i3 Center. The study was funded by the Wyss Institute at Harvard University, the Food and Drug Administration (under award #5R01FD006589), the National Cancer Institute of the NIH (under award #U54CA244726), as well as a fellowship from the Canadian Institutes of Health Research.
Recently I’ve been pondering how our mind’s expectations often block us from experiencing more richness and possibility. Even when we set goals and invite new desires, we can easily stop ourselves from taking accessible actions to advance. This month I ran into my own personal example of this phenomenon.
One aspirational goal that I set months ago was to eventually do an hour-long group training session at my gym called UltraFit. That class looked intimidating from the online videos I’d seen of it. You can see the description on the UltraFit web page if you’re curious, with lines like “Our most intense workout yet. Get ready to challenge your mental and physical limits.”
Here’s a 2-minute video preview of UltraFit:
The video includes such inviting phrases as:
“We created UltraFit to serve our high-intensity fitness fanatics.”
“UltraFit is advanced. It is no joke.”
“helps our competitive athletes stay in peak physical condition”
“We help them get through the hard work, the type of training that people don’t want to do on their own.”
Am I competitive athlete? No. But I loved the idea of building up enough fitness to handle this class – eventually. 😅
I’ve been doing GTX group training sessions with a few different trainers at this gym since Summer 2022, with some breaks for injury, illness, and travel. GTX stands for Group Training eXperience. Doing a 6am workout with other early risers who are into fitness is such a beautiful way to get my day started. I love the social aspect of working out with trainers and trainees in small groups.
GTX can be challenging, especially the Zone 4 sessions (higher heart rate exercises). UltraFit seemed pretty next-level relative to the GTX sessions though.
After some remodeling that our gym did in December, the UltraFit class which used to be on the third floor was moved down to the second floor – the floor where I normally do GTX sessions and also train on my own. Now the GTX and UltraFit sessions both use the same training area in the center of the second floor, so it’s much easier to observe.
Last Thursday morning when I was starting a cardio session on my own, I noticed that an UltraFit session was going to begin soon. I hopped on a treadmill close enough to observe. It seemed like a great opportunity to at least watch part of it, so I could form a clearer vision of what I might eventually build towards.
I was captivated from the start and ended up staying on that treadmill for 92 minutes, so I could watch the whole hour-long session. There were around seven people doing the training together.
I was using my Beats Fit Pro headphones to listen to an audiobook, but instead of only using noise cancelling mode, I sometimes switched to transparency mode. Transparency mode acts like a hearing aid, so it amplifies nearby sounds. This let me hear the trainer’s words more clearly, which gave me more insights into the training session.
By the end of it, I was thinking, that actually looks doable. I could surely do the first 45 minutes at least. The last 15 minutes looked tough, but I felt I could handle that too, although it was sure to get my heart rate pretty high. It wasn’t as intimidating in-person as it looked from the video, and the people actually doing the training didn’t look like the super fit athletes in the video either. They were generally fit, but not THAT fit.
I recognized a few of my fellow GTX trainees in UltraFit too, and I thought that if they could do it, so could I.
So I boldly signed up for the following week’s class. After I described what I saw and encouraged her to join me, Rachelle opted to try it with me too. We normally do the GTX sessions together – often enough that if we don’t show up together, the trainer will invariably ask us where the other one is.
We went to our first UltraFit session this morning at 6am.
The format was similar to the session I observed in its overall structure but with different exercises. It was challenging but doable, just as I thought. I couldn’t do all the moves perfectly – far from it – but I did my best. My heart rate peaked at 185 bpm, which is about as high as I’m physically capable of, so it really did push me to my limit in that regard.
In terms of intensity, it’s probably comparable to a Zone 4 GTX workout, which we just did yesterday. But whereas GTX has a more even, wave-like distribution of intensity, UltraFit starts fairly out mild and gradually builds to a peak of intensity over the course of the hour.
Each time we’d get on the treadmill, we’d sprint faster than before but for shorter durations, with sprinting rounds being 2 minutes, then 1 minute, then 45 seconds, 30 seconds, and the last couple of rounds being 15 seconds all out.
The hardest part was returning to the floor to do more high intensity exercises while still trying to catch my breath after sprinting fast at the end. The class had this flow of building up fatigue with round after round of sprinting and core exercises, and then you have to do more physical challenges while you’re already tired, and near the end, also breathless.
I liked the experience, which gave me a delightful sense of accomplishment afterwards, and Rachelle and I chatted with the instructor for a while afterwards. I’m sure I’ll do it again, maybe even next week. I like how it challenges me in different ways than the GTX sessions.
I wasn’t thinking that I’d accomplish my stretch goal of successfully completing an UltraFit class this soon. I figured it was still many months away. I’m glad I got the chance to visually audit the class first, which helped me picture myself just going for it.
This was a good reminder that our limits tend to be more mental than physical or financial. It’s amazing how our expectations can block us from opportunities and experiences that are more accessible than we realize.
What got me around that block in this case was exercising my curiosity to watch a class without having to commit to it. I leaned in to probe the goal a bit more, and that helped to crack my self-limiting thoughts about it.
That said, I might be pretty sore tomorrow unless my mind can find a way around that expectation too. 😉
The invitation for you is to consider how you might be blocking a seemingly distant stretch goal or desire due to your expectations regarding how you think it’s likely to show up. Are you piling on unnecessary prerequisites? How could you lean in with some noncommittal curiosity?
These expectation traps can be hard to spot within ourselves. One way to spot them is to ask where you wouldn’t feel that you belong. What experiences are other people having that you don’t feel ready for yet?
I had previously felt that I had to do a lot more training to earn the right to claim a spot in an UltraFit session. If I showed up before then, I’d surely be an impostor, right? I imagined a group of people like the ones in the video taking one look at me and saying, “Are you lost?” And that turned out to be pure fiction.
This morning I replaced the old frame with a new frame based on actual truth, including a fabulous UltraFit trainer named Gina encouraging Rachelle and me to come back for more. That feels like a lovely little graduation to have gone through – not physically as I had assumed would be necessary, but mentally and emotionally in terms of giving myself permission to access new experiences that were genuinely accessible.
I really think that LifeTime Athletic ought to consider replacing that video though. 🤣
Our roads might one day be safer thanks to a completely new type of system that overcomes some of lidar’s limitations. Lidar, which uses pulsed lasers to map objects and scenes, helps autonomous robots, vehicles and drones to navigate their environment. The new system represents the first time that the capabilities of conventional beam-scanning lidar systems have been combined with those of a newer 3D approach known as flash lidar.
In Optica, Optica Publishing Group’s journal for high-impact research, investigators led by Susumu Noda from Kyoto University in Japan describe their new nonmechanical 3D lidar system, which fits in the palm of the hand. They also show that it can be used to measure the distance of poorly reflective objects and automatically track the motion of these objects.
“With our lidar system, robots and vehicles will be able to reliably and safely navigate dynamic environments without losing sight of poorly reflective objects such as black metallic cars,” said Noda. “Incorporating this technology into cars, for example, would make autonomous driving safer.”
The new system is possible thanks to a unique light source the researchers developed called a dually modulated photonic-crystal laser (DM-PCSEL). Because this light source is chip-based it could eventually enable the development of an on-chip all-solid-state 3D lidar system.
“The DM-PCSEL integrates non-mechanical, electronically controlled beam scanning with flash illumination used in flash lidar to acquire a full 3D image with a single flash of light,” said Noda. “This unique source allows us to achieve both flash and scanning illumination without any moving parts or bulky external optical elements, such as lenses and diffractive optical elements.”
Combining scanning and flash illumination
Lidar systems map objects within view by illuminating those objects with laser beams and then calculating the distance of those objects by measuring the beams’ time of flight (ToF) — the time it takes for the light to travel to objects, be reflected and then return to the system. Most lidar systems in use and under development rely on moving parts such as motors to scan the laser beam, making these systems bulky, expensive and unreliable.
One non-mechanical approach, known as flash lidar, simultaneously illuminates and evaluates the distances of all objects in the field of view with a single broad, diffuse beam of light. However, flash lidar systems can’t be used to measure the distances of poorly reflective objects like black metallic cars due to the very small amount of light reflected from these objects. These systems also tend to be large because of the external lenses and optical elements needed to create the flash beam.
To address these critical limitations, the researchers developed the DM-PCSEL light source. It has both a flash source that can illuminate a wide 30°×30° field of view and a beam-scanning source that provides spot illumination with 100 narrow laser beams.
They incorporated the DM-PCSEL into a 3D lidar system, which allowed them to measure the distances of many objects simultaneously using wide flash illumination while also selectively illuminating poorly reflective objects with a more concentrated beam of light. The researchers also installed a ToF camera to perform distance measurements and developed software that enables automatic tracking of the motion of poorly reflective objects using beam-scanning illumination.
Measuring objects with varying reflectivity
“Our DM-PCSEL-based 3D lidar system lets us range highly reflective and poorly reflective objects simultaneously,” said Noda. “The lasers, ToF camera and all associated components required to operate the system were assembled in a compact manner, resulting in a total system footprint that is smaller than a business card.”
The researchers demonstrated the new lidar system by using it to measure the distances of poorly reflective objects placed on a table in a lab. They also showed that the system can automatically recognize poorly reflective objects and track their movement using selective illumination.
The researchers are now working to demonstrate the system in practical applications, such as the autonomous movement of robots and vehicles. They also want to see if replacing the ToF camera with a more optically sensitive single-photon avalanche photodiode array would allow the measurement of objects across even longer distances.
Why do some people get ADHD, while others do not? And how early in life or in the womb is the seed of ADHD sown?
Researchers from Aarhus University have come closer to answering this question in a large study, which has just been published in the journal Nature Genetics.
Together with national and international partners, the researchers have studied more than six million genetic variants in 38,691 people with ADHD and 186,843 people without ADHD. By this means it has been possible to identify 27 genetic risk variants for the common neurodevelopmental disorder.
Risk genes are expressed in the brain and neurons
The study is ground-breaking, inter alia because it finds more than twice as many risk variants as previous studies have identified.
The term “genetic variants” means specific variations in the DNA code — in this case, variants which are observed more frequently in people with ADHD than in people without the diagnosis. Variants in DNA affect, for example, the degree to which a gene is expressed and subsequently the amount of protein that is encoded by the gene.
By linking the genetic variants — i.e. the variations in DNA — to specific genes, the researchers have gained new knowledge about which tissues and cell types are particularly affected in individuals with ADHD. The study is based on data from the Danish iPSYCH cohort, deCODE Genetics in Iceland and the Psychiatric Genomics Consortium.
Subsequently, the researchers combined the results with existing data on gene expression in different tissues, cell types and brain development stages, and they discovered that genes involved in ADHD have a particularly high level of expression in a wide range of brain tissues and early in brain development — in fact already at the embryonic stage.
“This emphasises that ADHD should be seen as a brain developmental disorder, and that this is most likely influenced by genes that have a major impact on the brain’s early development,” says Professor Ditte Demontis of the Department of Biomedicine at Aarhus University, who is first author of the study.
In addition, the researchers found that the genetics that increase the risk of ADHD particularly affect genes that are expressed in neurons, especially dopaminergic neurons.
“This is interesting because dopamine plays a role in relation to the reward response in the brain, and because a frequently used form of ADHD medicine works by increasing the concentration of dopamine in different brain regions. Our results indicate that the imbalance in dopamine in the brains of people with ADHD is partly attributable to genetic risk factors,” says Ditte Demontis.
Associated with reduced concentration capacity and short-term memory
ADHD is influenced by many common genetic variants, each of which increases the risk slightly, says the professor.
In fact, with the help of advanced statistical models, the researchers have estimated that there are around 7,300 common genetic variants that increase the risk of ADHD. It is particularly interesting that the vast majority of these variants — 84-98 percent — also have an influence on other mental disorders, e.g. autism, depression and schizophrenia.
It has previously been shown that risk variants for ADHD can affect a person’s cognitive abilities.
To investigate this further, the researchers analysed data from an independent dataset, consisting of 4,973 people who had undergone extensive neuro-cognitive tests. By using information from the new study about which variants increase the risk of ADHD, they found in the independent data set that an increased load of ADHD risk variants in the genome of an individual is associated with reduced reading and mathematical abilities, reduced attention and reduced short-term memory.
“The results increase our knowledge of the biological mechanisms underlying ADHD, and they point to specific genes, tissues and cell types involved in ADHD. This knowledge can be used as a starting point for further studies of the disease mechanisms and identification of new drug targets,” explains Ditte Demontis.
And the study must be followed up, she emphasises.
“We have only mapped a small fraction of the common variants that influence ADHD — just 27 of the 7,300 that potentially exist. So there is a need for larger genetic studies,” she says.
International cross-disciplinary collaboration is the way forward
Large international collaborations are crucial to identifying the genetic causes of psychiatric diseases and neurodevelopmental disorders, because to do so requires studies of tens or hundreds of thousands of people with these conditions. Just as in the current ADHD study, there are often 100 or more researchers involved, with different areas of expertise, such as genetics, psychiatry, psychology, epidemiology, molecular biology, statistics, bioinformatics and computer science.
“In order to understand more of the genetic and biological mechanisms, it is important to have even larger studies, involving more people with ADHD,” says Professor Anders Børglum of the Department of Biomedicine, Aarhus University, who is the last author of the study and one of the research directors of the Danish iPSYCH project.
“But it is also important to undertake studies that focus on identifying how the genetic risk variants perturb biological processes in the brain cells (the neurons), and their way of joining up and communicating with each other in the brain. For the latter, both brain cells and early developmental stages of the brain, so-called mini-brains or brain organoids, are currently being examined” he says.
