Just 10% of kids with ADHD outgrow it

 Most children diagnosed with attention deficit hyperactive disorder (ADHD) don't outgrow the disorder, as widely thought. It manifests itself in adulthood in different ways and waxes and wanes over a lifetime, according to a study published Aug.13 in the American Journal of Psychiatry.

"It's important for people diagnosed with ADHD to understand that it's normal to have times in your life where things maybe more unmanageable and other times when things feel more under control," said lead researcher Margaret Sibley, associate professor of psychiatry and behavioral sciences at the University of Washington School of Medicine and a researcher at Seattle Children's Research Institute.

Study authors from 16 institutions in the United States, Canada, and Brazil said decades of research characterize ADHD as a neurobiological disorder typically first detected in childhood that persists into adulthood in approximately 50% of cases. But this study found just 10% of children completely outgrow it.

"Although intermittent periods of remission can be expected in most cases, 90% of children with ADHD in the Multimodal Treatment Study of ADHD continued to experience residual symptoms into young adulthood," they wrote.

ADHD is characterized by two main cluster of symptoms, according to researchers. The inattentive symptoms look like disorganization, forgetfulness, and having trouble staying on task. Then there are also the hyperactive, impulsive symptoms. In children, those symptoms look like having a lot of energy, such as running around and climbing on things. In adults, it manifests more as verbal impulsivity, difficulty with decision-making, and not thinking before acting. The disorder affects people differently and looks different depending on what phase of life someone's in.

Some people with ADHD also report a unique ability to hyper-focus. Olympic athletes Michael Phelps and Simone Biles have been open about their ADHD diagnosis.

While many people may experience symptoms similar to ADHD, it is estimated the disorder roughly affects 5% to 10% of the population, said Sibley.

16 years of research

This study followed a group of 558 children with ADHD for 16 years -- from 8-years old to 25 years-old. The cohort had eight assessments, every two years, to determine whether they had symptoms of ADHD. The researchers also asked their family members and teachers about their symptoms.

Sibley said the belief that 50% of children outgrow ADHD was first put forward in the mid-1990s. Most studies, she said, only re-connected with the kids one time in adulthood. So, researchers didn't get to see that the ADHD that they thought had gone away actually does come back.

Coping with ADHD

Researchers have yet to find what causes ADHD to flare. Sibley said it could be stress, the wrong environment, and not having a healthy lifestyle of proper sleep, healthy eating, and regular exercise. Also, if a person is not taking the time to manage symptoms and really understand what works best for them, then the symptoms are probably going to get more out of control, she said.

Medication and therapy are the two main treatment for ADHD. But, Sibley said, people can pursue their own healthy coping skills as well.

Researchers found that most people who technically no longer meet criteria for ADHD in adulthood still have some traces of ADHD, but they were managing well on their own.

"The key is finding a job or a life passion that ADHD does not interfere with," Sibley said. "You are going to see a lot of creative people have ADHD because they're able to be successful in their creative endeavors despite having ADHD, whereas people who might be required to do very detail-oriented work at a computer all day -- that could be a really hard combination for a person with ADHD."

Sibley said the time to seek professional help is when the symptoms are causing a problem in your life. This includes not performing your best, problems with other people, having a hard time getting along, difficulty maintaining healthy, long-term relationships with loved ones and friends, and inability to complete basic daily tasks -- whether that's parenting, staying on top of your finances, or just keeping an organized household.

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Story Source:

Materials provided by University of Washington School of Medicine/UW Medicine. Note: Content may be edited for style and length.

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Journal Reference:

1. Margaret H. Sibley, L. Eugene Arnold, James M. Swanson, Lily T. Hechtman, Traci M. Kennedy, Elizabeth Owens, Brooke S.G. Molina, Peter S. Jensen, Stephen P. Hinshaw, Arunima Roy, Andrea Chronis-Tuscano, Jeffrey H. Newcorn, Luis A. Rohde. Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD. American Journal of Psychiatry, 2021; appi.ajp.2021.2 DOI: 10.1176/appi.ajp.2021.21010032

https://www.sciencedaily.com/releases/2021/08/210813100258.htm

Brain cholesterol regulates Alzheimer's plaques

 A team co-led by scientists at Scripps Research has used advanced imaging methods to reveal how the production of the Alzheimer's-associated protein amyloid beta (Aβ) in the brain is tightly regulated by cholesterol.

Appearing on line Thursday ahead of print in the Aug. 17 issue of the Proceedings of the National Academy of Sciences (PNAS), the scientists' work advances understanding of how Alzheimer's disease develops and underscores the long-underappreciated role of brain cholesterol. The findings also help explain why genetic studies link Alzheimer's risk to a cholesterol-transporting protein called apolipoprotein E (apoE).

"We showed that cholesterol is acting essentially as a signal in neurons that determines how much Aβ gets made -- and thus it should be unsurprising that apoE, which carries the cholesterol to neurons, influences Alzheimer's risk," says study co-senior author Scott Hansen, PhD, an associate professor in the Department of Molecular Medicine at Scripps Research, Florida.

The other co-senior author of the study was Heather Ferris, MD, PhD, assistant professor in the Department of Medicine at the University of Virginia School of Medicine. The study's first author, Hao Wang, is a graduate student in the Hansen lab.

Understanding Aβ

A type of Aβ in the Alzheimer's brain can form large, insoluble aggregates that gather in extensive clumps or "plaques" -- one of the most prominent features of the disease at autopsy. Genetic evidence correlates the production of a subtype of Aβ with Alzheimer's, yet Aβ's role in both the healthy brain and in disease remain a subject of debate, after many clinical trials of Aβ-clearing therapeutics have struggled to show a benefit.

In the new study, Hansen and his colleagues take a close look cholesterol's connection to Aβ production. Cholesterol's role has been suggested by various prior studies but never confirmed directly, due to technological limitations. The scientists used an advanced microscopy technique called super-resolution imaging to "see," in cells and in the brains of live mice and tracked how cholesterol regulates Aβ production.

They focused on cholesterol produced in the brain by essential helper cells called astrocytes, and saw it was carried by apoE proteins to the outer membranes of neurons. There, it appeared to help maintain clusters of cholesterol and related molecules colloquially referred to as "lipid rafts." Lipid rafts are not yet well understood, in part because they are too tiny to image with ordinary light microscopes. With improved technology, they are increasingly appreciated as hubs where signaling molecules come together to carry out key cellular functions.

The protein from which Aβ is produced, APP, also sits in neuronal membranes. The researchers showed that apoE and its cholesterol cargo bring APP into contact with nearby lipid rafts. There, in the rafts, enzymes that cleave APP to form Aβ are found. They found that blocking the flow of cholesterol would take APP out of contact with lipid rafts, thereby effectively preventing Aβ production.

Cholesterol and brain health

The scientists then did a series of experiments in aged "3xTg-AD" mice, which are genetically engineered to overproduce Aβ, to develop Aβ plaques, and broadly to model Alzheimer's. They found that when they shut off astrocyte cholesterol production in the mice, Aβ production plummeted to near-normal, and Aβ plaques virtually disappeared. Another classic Alzheimer's sign usually seen in these mice is the accumulation of tangled aggregates of a neuronal protein called tau -- and those disappeared too.

By confirming and clarifying the role of astrocyte-produced cholesterol in Aβ production, the study suggests that targeting this process is worthy of exploration for potential to prevent Alzheimer's progression.

Hansen notes, however, that cholesterol is needed by the brain for many other processes, including the maintenance of normal alertness and cognition. His laboratory discovered in a 2020 study that severely interrupting the effect of cholesterol in neurons by general anesthetics can induce unconsciousness via a shared mechanism.

"You couldn't just eliminate cholesterol in neurons, cholesterol is needed to set a proper threshold for both Aβ production and normal cognition," Hansen says.

The findings offer new evidence of the underlying factors advancing development of Alzheimer's. A common variant of the apoE gene, known as the E4 variant, is the largest risk factor for late-onset Alzheimer's, and Hansen and colleagues found evidence in the study that this variant, compared to the more common, lower-risk E3 variant, somehow boosts APP's association with lipid rafts, which thus boosts Aβ production.

Hansen and his laboratory are currently studying how apoE's transport of cholesterol and maintenance of lipid rafts in the brain impacts not only Aβ production but also brain inflammation -- another feature of Alzheimer's that contributes to destruction in the brain but has murky causes.

"There is the suggestion here of a central mechanism, involving cholesterol, that could help explain why both Aβ plaques and inflammation are so prominent in the Alzheimer's brain," Hansen says.

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Story Source:

Materials provided by Scripps Research Institute. Note: Content may be edited for style and length.

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Journal Reference:

1. Hao Wang, Joshua A. Kulas, Chao Wang, David M. Holtzman, Heather A. Ferris, Scott B. Hansen. Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol. Proceedings of the National Academy of Sciences, 2021; 118 (33): e2102191118 DOI: 10.1073/pnas.2102191118

https://www.sciencedaily.com/releases/2021/08/210813151957.htm

Solving structure of BRCA2 protein complex important in DNA repair

 The initials BRCA2 may be best known for a gene associated with many cases of breast cancer, and the protein encoded by the BRCA2 gene is critical to repairing breaks in DNA.

The breakdown of this interaction is a hallmark of many cancers. Now, U-M scientists have determined the structure of a complex of two proteins -- BRCA2 together with MEILB2 -- that allows repairs to happen efficiently in cells undergoing cell-splitting, called meiosis. Their results, reported in Nature Structural and Molecular Biology, have major implications for cancer and infertility.

"We know how the literature is rich with examples of BRCA2 mutations in cancer, but our findings now suggest that the MEILB2-binding region of BRCA2 might be a hotspot for discovering mutations related to infertility," said study author and U-M structural biologist Jayakrishnan Nandakumar, associate professor of molecular, cellular, and developmental biology.

In germ cells -- the cells that give rise to sperm or eggs -- DNA breaks occur in every chromosome before the cells undergo meiosis. The breaks ensure mixing of genes to create genetic diversity rather than exact copies of the parents. In meiosis, each germ cell splits twice so that each egg or sperm ends up with only one copy of each chromosome. Then when egg meets sperm, the embryo has the right number of chromosome pairs.

Before the first split occurs, the chromosomes in the germ cell pair up tightly and then each chromosome within a pair breaks and rejoins with pieces from its partner to exchange genes in a process called crossover. Then all these DNA breaks need to be rejoined quickly.

Think of a sandwich, Nandakumar explains. The "bun" is composed of four identical copies of a protein called MEILB2 on the top and bottom, with the two BRCA2 proteins between. The MEILB2 protein sandwich carries the BRCA2 protein precisely to the DNA break points.

To determine the structure of this BRCA2 complex, the researchers used X-ray crystallography. In this process, the protein crystal is bombarded with X-rays and the patterns that are generated when the X-rays deflect off the atoms in the crystal allow the researchers to figure out where each atom is located in the 3D structure of the molecule. That would help them figure out how the BRCA2 protein is connected to the MEILB2 protein.

The first step was to grow crystals of the BRCA2 complex. After much trial and error, Devon Pendlebury, a chemical biology graduate student in the Nandakumar lab, successfully crystallized the human form of the BRCA2 complex. In a bit of good fortune, the U-M researchers were able to collect data at the Argonne National Laboratory days before all research was shut down in March 2020.

From the X-ray crystallography data and additional experiments by MCDB graduate student Ritvija Agrawal, the team determined the structure of the protein complex and how the two proteins worked together. It was a somewhat unusual protein-interaction, they report.

To validate their findings, they created mutant versions of BRCA2 and MEILB2 based on their structure and showed how these mutants failed to form this complex with each other.

In further validation of the MEILB2-BRCA2 complex structure, collaborators at the University of Gothenburg in Sweden introduced equivalent mutant versions in mouse cells undergoing meiosis. Mutant BRCA2 or MEILB2 failed to get to the DNA breaks that needed to be rejoined.

"While we have known BRCA2 was necessary for DNA recombination in meiosis, we didn't know how it was able to do this critical job efficiently," Nandakumar said. "The MEILB2 that is part of this repair complex is only supposed to be present in cells that undergo meiosis but MEILB2 has also been found in several cancers. It may be that MEILB2 is very efficiently 'hijacking' the BRCA2 in cancer cells, preventing proper repair of the DNA."

Without other factors usually found in meiotic cells, the BRCA2 in these MEILB2-positive cancers might not get to the DNA breakpoints. Having a structure of this complex in hand, researchers may now find new approaches to regain BRCA2 function in MEILB2-positive cancers, Nandakumar suggests.

Co-authors include Hiroki Shibuya, an assistant professor in the Department of Chemistry and Molecular Biology at the University of Gothenburg.

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Story Source:

Materials provided by University of Michigan. Original written by Suzanne Tainter. Note: Content may be edited for style and length.

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Journal Reference:

1. Devon F. Pendlebury, Jingjing Zhang, Ritvija Agrawal, Hiroki Shibuya, Jayakrishnan Nandakumar. Structure of a meiosis-specific complex central to BRCA2 localization at recombination sites. Nature Structural & Molecular Biology, 2021; 28 (8): 671 DOI: 10.1038/s41594-021-00635-0

https://www.sciencedaily.com/releases/2021/08/210813120006.htm

Biomarkers may detect early eye changes leading to diabetes-related blindness

 New biomarkers found in the eyes could unlock the key to helping manage diabetic retinopathy, and perhaps even diabetes, according to new research conducted at the Indiana University School of Optometry.

During its early stages, diabetes can affect the eyes before the changes are detectable with a regular clinical examination. However, new retinal research has found that these changes can be measured earlier than previously thought with specialized optical techniques and computer analysis.

The ability to detect biomarkers for this sight-threatening condition may lead to the early identification of people at risk for diabetes or visual impairment, as well as improve physicians' ability to manage these patients. The study appears in the journal PLOS One.

"Early detection of retinal damage from diabetes is possible to obtain with painless methods and might help identify undiagnosed patients early enough to diminish the consequences of uncontrolled diabetes," said study co-author Ann E. Elsner, a Distinguished Professor at the IU School of Optometry.

Diabetic retinopathy, which is caused by changes in the blood vessels in the retina, is the most common diabetic eye disease and a leading cause of blindness in U.S. adults. From 2010 to 2050, the number of Americans with diabetic retinopathy is expected to nearly double, from 7.7 million to 14.6 million.

The new study is part of the current widespread emphasis on detection of diabetic retinopathy through artificial intelligence applied to retinal images. However, some of these algorithms provide detection based on features that occur much later than the changes found in this study.

The IU-led method advances earlier detection because of the retinal image processing algorithms described in the study.

"Many algorithms use any image information that differs between diabetic patients and controls, which can identify which individuals might have diabetes, but these can be nonspecific," Elsner said. "Our method can be combined with the other AI methods to provide early information localized to specific retinal layers or types of tissues, which allows inclusion of information not analyzed in the other algorithms."

Elsner conducted the retinal image analysis in her lab at the IU School of Optometry's Borish Center for Ophthalmic Research, along with her co-author, Joel A. Papay, a Ph.D. student in the Vision Science Program at the school. They used data collected from volunteers with diabetes, along with healthy control subjects. Additional data were also collected from a diabetic retinopathy screening of members of the underserved community at the University of California, Berkeley, and Alameda Health.

The computer analysis was performed on retinal image data commonly collected in well-equipped clinics, but much of the information used in this study is often ignored for diagnosis or management of patients.

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Story Source:

Materials provided by Indiana University. Note: Content may be edited for style and length.

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Journal Reference:

1. Joel A. Papay, Ann E. Elsner. Quantifying frequency content in cross-sectional retinal scans of diabetics vs. controls. PLOS ONE, 2021; 16 (6): e0253091 DOI: 10.1371/journal.pone.0253091

https://www.sciencedaily.com/releases/2021/08/210813105533.htm

Biden administration plans for vaccine boosters, perhaps by fall

 The administration of U.S. President Joe Biden is developing a plan to start offering coronavirus booster shots to some Americans as early as this fall, the New York Times reported on Saturday, citing people familiar with the effort.

The first boosters are likely to go to nursing home residents and health care workers, followed by other older people who were near the front of the line when vaccinations began late last year, the newspaper reported.

Officials envision giving people the same vaccine they originally received. They have discussed starting the effort in October but have not settled on a timetable, the report added.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Moderna-Biden-administration-plans-for-vaccine-boosters-perhaps-by-fall-NYT-36165738/

W.Va. officials want COVID booster shot for all 50 and over

 The Food and Drug Administration has OKed a third COVID shot for Americans with compromised immune systems.

In West Virginia, state officials are pushing to extend those booster shots to everyone 50 and older.

With concern that immunizations lose some of their effectiveness over time, the FDA and Centers for Disease Control and Prevention are focused on weighing the need for booster shots of those with compromised immune systems such as organ transplant patients.

But West Virginia, which vaccinated its most vulnerable early, is pushing to expand booster shots to all West Virginians over 50 years old.

“We are pressing the CDC and the FDA to make sure that they work diligently to open up to 50 and above - all individuals - so that we can start that booster process,” James Hoyer, director of the Joint Interagency Task Force. “We know in West Virginia, even with the delta variant, 97 percent of our deaths and our hospitalizations have historically come from age 50 and above. "

It's been seven months since many nursing home patients got the shot.

Kanawha County officials said they could move ahead with the third shot as early as a Saturday drive-thru clinic scheduled at the Kanawha-Charleston Health Department, but that is unlikely to happen because CDC approval would still be required after FDA action.

“CDC will hold a meeting of its advisory committee on immunization practices tomorrow to discuss this issue and offer their expert insights and recommendations,” Dr. Rochelle Walensky, director of the CDC, said.

Experts said no vaccine lasts forever, but officials dealing with the pandemic in West Virginia want a broader booster target than the 3% with immunocompromised systems.

https://wchstv.com/news/local/no-greenlight-yet-but-wva-officials-want-covid-booster-shot-for-all-50-and-over

Companies eye charging unvaccinated employees more for health coverage

 Health analysts are saying that companies may begin charging unvaccinated employees more for their health insurance as the highly contagious delta variant fuels more COVID-19 cases and hospitalizations across the country. 

Similar to the higher insurance premiums smokers may face due to being deemed a greater health risk, companies are now looking at the potential costs their unvaccinated employees may face should they get infected with COVID-19 and require medical treatment. 

Wade Symons, a partner at benefits consulting firm Mercer Health, told CBS MoneyWatch on Friday that he expects some employers to increase health premiums for unvaccinated workers by as much as $20 to $50 per paycheck. 

"Unvaccinated individuals have potential to cost the employer more from a health care spend perspective," Symons explained, adding that "an individual with a tough COVID case" could get a hospital bill as high as $50,000. 

The health insurance consultant said that a higher health premium for an unvaccinated worker "allows a company to say, 'OK, you have a choice to do it or not, but if you don't there will be a surcharge you have to pay.'"

"So it feels a little better from the employer's perspective to be able to say, 'We're not mandating it, but we want to nudge you along the road to getting vaccinated,'" he told CBS. 

Kaiser Health News (KHN) also reported last week that while most major private insurance companies initially waived patient payments for COVID-19 treatment, several have allowed the policy to lapse following the emergency use authorizations granted to three COVID-19 vaccines. 

Aetna ended its insurance waiver policy at the end of February, and UnitedHealthcare officially stopped its waivers in March after rolling back the policy for months, according to KHN.

The deliberations among companies come as hospitals across the country say that the vast majority of new COVID-19 patients are among those who remain unvaccinated. 

According to research published Thursday by the Indeed Hiring Lab, the number of job openings posted that required potential applicants to be vaccinated nearly doubled between July and August. 

President Biden has issued a vaccine requirement for federal employees, a decision that was followed by a number of state and local governments deciding to do the same. 

The day after Biden’s announcement, Walt Disney Co. said all of its employees would need to get the COVID-19 vaccine within two months, and Walmart, the country’s largest private employer, said it would require vaccinations among its workers at the company’s headquarters in Arkansas.

https://thehill.com/policy/healthcare/567871-companies-mulling-charging-unvaccinated-employees-more-for-health-coverage