Monday, March 18, 2019
NIH study finds new cell composition may lead to less effective future response
Meningitis, a group of serious diseases which infect the brain’s lining, leaves its mark and can affect the body’s ability to fight such infections in the future. According to a new study published in Nature Immunology, infections can have long-lasting effects on a population of meningeal immune cells, replacing them with cells from outside the meninges that then change and become less likely to recognize and ward off future attacks. The research was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
“After an infection, the immune cell landscape in the brain lining changes. Brain lining immune cells that normally protect the brain from foreign invaders die and are replaced by cells from elsewhere in the body. These new cells are altered in a way that affects how they respond to subsequent challenges and new infections,” said Dorian McGavern, Ph.D., NINDS scientist and senior author of the study.
Using real time imaging, Dr. McGavern and his colleagues took a detailed look at mouse meningeal macrophages, which are immune cells that live in the meninges, the protective layers covering the brain and spinal cord. One group of these macrophages is found along blood vessels in the dura mater (the outermost layer of the meninges) and helps catch pathogens from the blood before they reach brain tissue. Blood vessels in the dura mater are relatively open compared to the tightly sealed vessels found in other brain regions, and macrophages in the dura mater often serve as the first line of defense against harmful blood-borne agents.
Meningeal macrophages (shown in white, red, and blue) are on constant alert against potential threats to brain tissue.
Wednesday, March 13, 2019
Using fMRI, researchers uncover the neural underpinnings, which could aid development of potential treatments
Researchers have identified changes in brain connectivity and brain activity during rest and reward anticipation in children with anhedonia, a condition where people lose interest and pleasure in activities they used to enjoy. The study, by scientists at the National Institute of Mental Health (NIMH), part of the National Institutes of Health, sheds light on brain function associated with anhedonia and helps differentiate anhedonia from other related aspects of psychopathology. The findings appear in the journal JAMA Psychiatry.
Anhedonia is a risk factor for, and a symptom of, certain mental disorders and is predictive of illness severity, resistance to treatment, and suicide risk. While researchers have sought to understand the brain mechanisms that contribute to anhedonia, investigations on this condition have more commonly focused on adults rather than children. Importantly, previous studies often did not separate anhedonia from other related psychopathologies, such as low mood, anxiety, or attention-deficit/hyperactivity disorder.
“Understanding the neural mechanisms of anhedonia that are distinguishable from other psychiatric concerns is important for clinicians to develop on-target treatments,” said lead study author Narun Pornpattananangkul, Ph.D., a postdoctoral fellow in the Emotion and Development Branch, part of NIMH’s Division of Intramural Research Programs. “Yet, disentangling shared characteristics from unique neural mechanisms of anhedonia is challenging because it often co-occurs with other psychiatric conditions.”
Image showing differences in fMRI activation between children with and without anhedonia during reward-anticipation.
Tuesday, March 12, 2019
These exceptional early stage scientists continue agency commitment to the next generation of biomedical researchers
The National Institutes of Health has selected eight scientists as Lasker Clinical Research Scholars, part of a joint initiative with the Albert and Mary Lasker Foundation, to foster the next generation of great clinical scientists. This highly competitive program provides talented, early stage researchers the opportunity to carry out independent clinical and translational research for five to seven years at NIH. The researchers also have the possibility of additional years of financial support, at NIH or an NIH-funded research institution, upon project review. The new researchers join 15 Lasker Scholars hired since 2012.
“Adding to the impressive cadre of Lasker Scholars at NIH, these new clinician-scientists will continue to produce innovative discoveries that affirm our investment in some of the boldest young minds in biomedical research,” said NIH Director Francis S. Collins, M.D., Ph.D.
Lasker Scholars have access to the NIH Clinical Center, the largest hospital in the world devoted to clinical research. The Lasker Foundation will provide additional developmental support to the scholars while they are working at NIH by funding travel to scientific meetings and providing the opportunity to participate in selected foundation activities, including the Lasker Award ceremonies.
The eight new Lasker Scholars are: Catherine Cukras, M.D., Ph.D., National Eye Institute (NEI); John Dekker, M.D., Ph.D., National Institute of Allergy and Infectious Diseases (NIAID); Christopher Kanakry, M.D., National Cancer Institute (NCI); Jonathan Lyons, M.D., NIAID; Sonja Scholz, M.D., Ph.D., National Institute of Neurological Disorders and Stroke (NINDS); Nida Sen, M.D., NEI; Jack Shern, M.D., NCI; and Jing Wu, M.D., Ph.D., NCI.
Learn about the research each new Lasker Scholar is pursuing.
Monday, March 11, 2019
Findings highlight the importance of screening kids as young as 10 for suicide risk in emergency settings
A research team found nearly one-third of youth ages 10 to 12 years screened positive for suicide risk in emergency department settings. As part of a larger study on youth suicide risk screening in emergency departments, researchers at the National Institute of Mental Health (NIMH), part of the National Institutes of Health, and collaborators sought to explore how frequently preteen youth ages 10 to 12 screened positive for suicide risk. Notably, seven percent of the preteens who screened positive for suicide risk were seeking help for physical – not psychiatric – concerns. The study appears online March 11 in Hospital Pediatrics.
“Typically, suicidal thoughts and behaviors are seen in older teens. It was troubling to see that so many preteens screened positive for suicide risk, and we were alarmed to find that many of them had acted on their suicidal thoughts in the past,” said Lisa Horowitz, Ph.D., M.P.H., a clinical scientist in the NIMH Division of Intramural Research Programs (DIRP) and an author on the paper. “This study shows that children as young as 10 who show up in the emergency department may be thinking about suicide, and that screening all preteens — regardless of their presenting symptoms — may save lives. Otherwise, they may pass through our medical systems undetected.”
Monday, March 4, 2019
Assessing the patterns of energy use and neuronal activity simultaneously in the human brain improves our understanding of how alcohol affects the brain, according to new research by scientists at the National Institutes of Health. The new approach for characterizing brain energetic patterns could also be useful for studying other neuropsychiatric diseases. A report of the findings is now online in Nature Communications.
“The brain uses a lot of energy compared to other body organs, and the association between brain activity and energy utilization is an important marker of brain health,” said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of NIH, which funded the study. “This study introduces a new way of characterizing how brain activity is related to its consumption of glucose, which could be very useful in understanding how the brain uses energy in health and disease.”
The research was led by Dr. Ehsan Shokri-Kojori and Dr. Nora D. Volkow of the NIAAA Laboratory of Neuroimaging. Dr. Volkow is also the director of the National Institute on Drug Abuse at NIH. In previous studies they and their colleagues have shown that alcohol significantly affects brain glucose metabolism, a measure of energy use, as well as regional brain activity, which is assessed through changes in blood oxygenation.
“The findings from this study highlight the relevance of energetics for ensuring normal brain function and reveal how it is disrupted by excessive alcohol consumption,” says Dr. Volkow.
NIH scientists present a new method for combining measures of brain activity (left) and glucose consumption (right) to study regional specialization and to better understand the effects of alcohol on the human brain.
Monday, February 25, 2019
IRP study also suggests that handling a cell phone doubles teen driver crash risk
Teenagers who reach for objects, such as food or makeup, while driving increase their risk of crashing nearly seven times, according to researchers at the National Institutes of Health. Their study, which appears in the American Journal of Preventative Medicine, also found that manually dialing, texting or browsing the web on a phone while driving doubled a teen’s crash risk.
Motor vehicle crashes are the leading cause of death and disabilities among drivers aged 15 to 20 years, according to the National Highway Traffic Safety Administration. The current study is the first to use real-time driving data to quantify the extent to which visual inattention — the amount of time a teen’s eyes shift from the road to various distractions — contributes to the risk of a crash.
Researchers followed 82 newly licensed teen drivers in Virginia over a one-year period, equipping their vehicles with cameras and GPS technology to track the driver’s activity and environment. After one year, 43 of the drivers did not experience a crash, while 25 had one crash and 14 had two or more crashes. Using six-second videos of driver behavior prior to a crash, researchers calculated that for every second that a teen’s eyes were off the road, the risk of a crash increased by 28 percent regardless of the type of distraction. Teens manually using a cell phone doubled their odds of crashing. Teens who were reaching for something while driving increased their risk nearly sevenfold, which researchers attributed to a combination of distractions, including taking their eyes off the road and their hands off the wheel.
“Teenage drivers are so comfortable with mobile devices that they tend to overestimate their ability to multitask while driving,” said Bruce Simons-Morton, M.P.H., Ed.D., a senior investigator at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and one of the authors of the study.
Friday, February 22, 2019
IRP scientists use epigenetics to help predict disease development
Biologic age, a DNA-based estimate of a person’s age, is associated with future development of breast cancer, according to scientists at the National Institutes of Health. Biologic age was determined by measuring DNA methylation, a chemical modification to DNA that is part of the normal aging process. The study showed for every five years a woman’s biologic age was older than her chronologic or actual age, known as age acceleration, she had a 15 percent increase in her chance of developing breast cancer. The study was published online Feb. 22 in the Journal of the National Cancer Institute.
Scientists from the National Institute of Environmental Health Sciences (NIEHS), part of NIH, speculate that biologic age may be tied to environmental exposures. If so, it may be a useful indicator of disease risk. They used three different measures, called epigenetic clocks, to estimate biologic age. These clocks measure methylation found at specific locations in DNA. Researchers use these clocks to estimate biologic age, which can then be compared to chronologic age.
The researchers used DNA from blood samples provided by women enrolled in the NIEHS-led Sister Study, a group of more than 50,000 women in the U.S. and Puerto Rico. The study was specifically designed to identify environmental and genetic risk factors for breast cancer. The research team measured methylation in a subset of 2,764 women, all of whom were cancer-free at the time of blood collection.
"We found that if your biologic age is older than your chronologic age, your breast cancer risk is increased. The converse was also true. If your biologic age is younger than your chronologic age, you may have decreased risk of developing breast cancer," said corresponding author Jack Taylor, M.D., Ph.D., head of the NIEHS Molecular and Genetic Epidemiology Group. "However, we don’t yet know how exposures and lifestyle factors may affect biologic age or whether this process can be reversed."
If a woman’s biologic age is older than her chronologic age, she has an increased risk of developing breast cancer.
Wednesday, February 20, 2019
IRP clinical study results suggest the drug could help protect skin and prevent vision problems
A small pilot clinical study at the National Eye Institute (NEI) suggests that the drug nitisinone increases melanin production in some people with oculocutaneous albinism type 1B (OCA-1B), a rare genetic disease that causes pale skin and hair and poor vision. Increased melanin could help protect people with the condition against the sun’s UV rays and promote the development of normal vision. Study results were published in JCI Insight. NEI is part of the National Institutes of Health (NIH).
“Because the greatest vision problems for people with albinism occur during the early development of the eye, our eventual goal is to work with infants,” said Brian Brooks, M.D., Ph.D., clinical director at NEI and lead author of the study. “The purpose of this pilot study was to explore whether nitisinone is safe and whether we could pick up a signal that the drug works.”
Study participant has darker hair after six months on nitisinone (right), compared to baseline (left).
Friday, February 15, 2019
FDA- and NIH-funded study finds unexpected sensory variant exclusive to African-Americans
A genetic variant found only in people of African descent significantly increases a smoker’s preference for cigarettes containing menthol, a flavor additive. The variant of the MRGPRX4 gene is five to eight times more frequent among smokers who use menthol cigarettes than other smokers, according to an international group of researchers supported by the U.S. Food and Drug Administration and the National Institutes of Health. The multiethnic study is the first to look across all genes to identify genetic vulnerability to menthol cigarettes. The paper was published online in the journal PLOS Genetics(link is external) on Feb. 15.
Menthol provides a minty taste and a cooling or soothing sensation, and plays a particularly troubling role in U.S. cigarette smoking patterns. According to the FDA, nearly 20 million people in the United States smoke menthol cigarettes, which are particularly popular among African-American smokers and teen smokers. In the U.S., 86 percent of African-American smokers use menthol cigarettes, compared to less than 30 percent of smokers of European descent. In addition, menthol cigarettes may be harder to quit than other cigarettes.
Although not originally the focus of the study, researchers also uncovered clues as to how menthol may reduce the irritation and harshness of smoking cigarettes.
“This study sheds light on the molecular mechanisms of how menthol interacts with the body,” said Andrew Griffith, M.D., Ph.D., scientific director and acting deputy director of NIH’s National Institute on Deafness and Other Communications Disorders (NIDCD). “These results can help inform public health strategies to lower the rates of harmful cigarette smoking among groups particularly vulnerable to using menthol cigarettes.”
The research team, led by Dennis Drayna, Ph.D., chief of the Section on Genetics of Communication Disorders at the NIDCD, conducted detailed genetic analyses on 1,300 adults. In the initial analyses, researchers at the University of Texas Southwestern Medical Center, Dallas (UT Southwestern), used data from a multiethnic, population-based group of smokers from the Dallas Heart Study and from an African-American group of smokers from the Dallas Biobank. In conjunction with researchers from the Schroeder Institute® for Tobacco Research, Washington, D.C., the scientists further confirmed their findings in a group of African-American smokers enrolled in the Washington, D.C., Tobacco QuitlineTM.
Wednesday, February 13, 2019
Researchers measured pain’s impact on normal work activities, people’s health status, and health care use
Prompted by a call from the National Academy of Medicine, then the Institute of Medicine, for improved national data on pain, a recent study provides new insights concerning pain trends and opioid use for pain management. Researchers used data from the Medical Expenditure Panel Survey (MEPS) to examine the impact of pain-related interference, a measure of pain’s impact on normal work activities, on people’s health status and health care use. MEPS is a nationally representative survey of the U.S. civilian, noninstitutionalized population.
Researchers showed that the number of U.S. adults age 18 and older suffering from at least one painful health condition increased substantially from 120.2 million (32.9 percent) in 1997/1998 to 178 million (41 percent) in 2013/2014. Furthermore, the use of strong opioids, like fentanyl, morphine, and oxycodone, for pain management among adults with severe pain-related interference more than doubled from 4.1 million (11.5 percent) in 2001/2002 to 10.5 million (24.3 percent) in 2013/2014. These are the findings of a comprehensive analysis of 18-year trends showing changes in the overall rates of noncancer pain prevalence and management. The full study, conducted by the National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health; Social & Scientific Systems, Inc., Silver Spring, Maryland; and Yale University School of Medicine, New Haven, Connecticut; was published in the Journal of Pain.
“We took a unique approach with this study by simultaneously examining long-term trends in the overall prevalence of noncancer pain in the U.S., the impact of this pain, and health care use attributable directly to pain management,” says Richard L. Nahin, Ph.D., first author on the study and NCCIH lead epidemiologist. “To address these gaps, we used data from MEPS to identify trends between 1997 and 2014.”