Research advances from the National Institutes of Health (NIH) Intramural Research Program (IRP) often make headlines. Read the news releases that describe our most recent findings:
People taking the mineral for other medical reasons should stay the course
Eating a calcium-rich diet or taking calcium supplements does not appear to increase the risk of age-related macular degeneration (AMD), according to the findings of a study by scientists at the National Eye Institute (NEI). AMD is a leading cause of vision loss and blindness among people age 65 and older in the United States. The study findings are published in JAMA Ophthalmology.
The findings contradict an earlier study indicating that high levels of calcium were associated with increased prevalence of AMD, but they are consistent with another suggesting that calcium has a protective role in AMD.
“Although the findings suggest that high calcium intake may be protective, the jury is still out on whether people should alter their calcium intake to prevent the onset or progression of AMD,” said the study’s lead investigator, Emily Chew, M.D., director of the Division of Epidemiology and Clinical Applications and the deputy clinical director at NEI, which is part of the National Institutes of Health.
Calcium-rich foods include milk, yogurt and cheese, as well as non-dairy sources such as kale, white beans and sesame seeds.
Approximately 1 in 9 women in the United States experiences symptoms of postpartum depression, according to the Centers for Disease Control and Prevention. Now, the U. S. Food and Drug Administration (FDA) has approved brexanolone, an analog of the endogenous human hormone allopregnanolone and the first drug specifically designed to treat postpartum depression.
Some psychiatric drugs owe their discovery to chance — serendipitous observations of clinical benefit — or a process of incremental improvement based on drugs previously discovered by chance. Not so with brexanolone, which has a truly novel mechanism of action and was developed by design, thanks to a series of basic and translational neuroscience studies. FDA approval represents the final phase of a bench-to-bedside journey for this drug — a journey that began in the NIMH Intramural Research Program (IRP).
In the 1980s, NIMH IRP researchers discovered that metabolites (products formed when the body breaks down or “metabolizes” other substances) of the steroid hormones progesterone and deoxycorticosterone bound to and acted upon receptors for gamma-aminobutyric acid (GABA) — a major inhibitory neurotransmitter in the brain. These steroids were found to amplify GABA-activated chloride ion currents, thereby impacting the excitability of neurons.
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.
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.
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.
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.”
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.
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.
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.
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).
