In the News

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:

Analysis of social media language using AI models predicts depression severity for white Americans, but not Black Americans

NIH-supported study also found Black people with depression used different language compared to white people to express their thoughts on Facebook

Researchers were able to predict depression severity for white people, but not for Black people using standard language-based computer models to analyze Facebook posts. Words and phrases associated with depression, such as first-person pronouns and negative emotion words, were around three times more predictive of depression severity for white people than for Black people. The study, published today in the Proceedings of the National Academy of Sciences, is co-authored by researchers at the University of Pennsylvania, Philadelphia, and the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), which also funded the study.

While previous research has indicated that social media language could provide useful information as part of mental health assessments, the findings from this study point to potential limitations in generalizing this practice by highlighting key demographic differences in language used by people with depression. The results also highlight the importance of including diverse pools of data to ensure accuracy as machine learning models, an application of artificial intelligence (AI) language models, are developed.

“As society explores the use of AI and other technologies to help deliver much-needed mental health care, we must ensure no one is left behind or misrepresented,” said Nora Volkow, M.D., NIDA director. “More diverse datasets are essential to ensure that healthcare disparities are not perpetuated by AI and that these new technologies can help tailor more effective health care interventions.”

Experimental gene therapy for giant axonal neuropathy shows promise in NIH clinical trial

Treatment for rare childhood disease was well tolerated and slowed loss of motor function

An investigational gene therapy for a rare neurodegenerative disease that begins in early childhood, known as giant axonal neuropathy (GAN), was well tolerated and showed signs of therapeutic benefit in a clinical trial led by the National Institutes of Health (NIH). Currently, there is no treatment for GAN and the disease is usually fatal by 30 years of age. Fourteen children with GAN, ages 6 to 14 years, were treated with gene transfer therapy at the NIH Clinical Center and then followed for about six years to assess safety. Results of the early-stage clinical trial appear in the New England Journal of Medicine

The gene therapy uses a modified virus to deliver functional copies of the defective GAN gene to nerve cells in the body. It is the first time a gene therapy has been administered directly into the spinal fluid, allowing it to target the motor and sensory neurons affected in GAN. At some dose levels, the treatment appeared to slow the rate of motor function decline. The findings also suggest regeneration of sensory nerves may be possible in some patients. The trial results are an early indication that the therapy may have favorable safety and tolerability and could help people with the rapidly progressive disease.

“One striking finding in the study was that the sensory nerves, which are affected earliest in GAN, started ‘waking up’ again in some of the patients,” said Carsten G. Bonnemann, M.D., senior author and chief of the Neuromuscular and Neurogenetic Disorders of Childhood Section at the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH. “I think it marks the first time it has been shown that a sensory nerve affected in a genetic degenerative disease can actually be rescued with a gene therapy such as this.”

Biopsy of a sensory nerve from a participant in the GAN gene therapy trial

Biopsy of a sensory nerve from a participant in the GAN gene therapy trial (arrows indicate giant axons; regenerating nerve cluster in upper left). Some patients regained sensory nerve response after treatment.

Inflammation-reducing drug shows no benefit for dry age-related macular degeneration in NIH trial

The drug minocycline, an antibiotic that also decreases inflammation, failed to slow vision loss or expansion of geographic atrophy in people with dry age-related macular degeneration (AMD), according to a phase II clinical study at the National Eye Institute (NEI), part of the National Institutes of Health.

Dry AMD affects the macula, the part of the eye’s retina that allows for clear central vision. In people with dry AMD, patches of light-sensing photoreceptors and their nearby support cells begin to die off, leaving regions known as geographic atrophy. Over time, these regions expand, causing people to lose more and more of their central vision. Microglia, immune cells that help maintain tissue and clear up debris, are present at higher levels around damaged retinal regions in people with dry AMD than in people without AMD. Scientists have suggested that inflammation — and particularly microglia — may be driving the expansion of geographic atrophy regions.

This study, led by Tiarnan Keenan, M.D., Ph.D., a Stadtman Tenure-Track Investigator at the NEI’s Division of Epidemiology and Clinical Applications, tested whether inhibiting microglia with minocycline might help slow geographic atrophy expansion and its corresponding vision loss. The trial enrolled 37 participants at the NIH Clinical Center in Bethesda, Maryland, and at the Bristol Eye Hospital, United Kingdom. After a nine-month period where the researchers tracked each participant’s rate of geographic atrophy expansion, the participants took twice-daily doses of minocycline for two years. The researchers compared each participant’s rate of geographic atrophy expansion while taking minocycline to their baseline rate, and found there was no difference in geographic atrophy expansion rate or vision loss with minocycline.

Retina, showing a large region of geographic atrophy

Retina, showing a large region of geographic atrophy.

IRP studies find severe symptoms of 'Havana Syndrome,' but no evidence of MRI-detectable brain injury or biological abnormalities

Compared to healthy volunteers, affected U.S. government personnel did not exhibit differences that would explain symptoms

Using advanced imaging techniques and in-depth clinical assessments, a research team at the National Institutes of Health (NIH) found no significant evidence of MRI-detectable brain injury, nor differences in most clinical measures compared to controls, among a group of federal employees who experienced anomalous health incidents (AHIs). These incidents, including hearing noise and experiencing head pressure followed by headache, dizziness, cognitive dysfunction and other symptoms, have been described in the news media as 'Havana Syndrome' since U.S. government personnel stationed in Havana first reported the incidents. Scientists at the NIH Clinical Center conducted the research over the course of nearly five years and published their findings in two papers in JAMA today.

“Our goal was to conduct thorough, objective and reproducible evaluations to see if we could identify structural brain or biological differences in people who reported AHIs,” said Leighton Chan, M.D., chief, rehabilitation medicine and acting chief scientific officer, NIH Clinical Center, and lead author on one of the papers. “While we did not identify significant differences in participants with AHIs, it’s important to acknowledge that these symptoms are very real, cause significant disruption in the lives of those affected and can be quite prolonged, disabling and difficult to treat.”

Researchers designed multiple methods to evaluate more than 80 U.S. government employees and their adult family members, mostly stationed abroad, who had reported an AHI and compared them to matched healthy controls. The control groups included healthy volunteers who had similar work assignments but did not report AHIs. In this study, participants underwent a battery of clinical, auditory, balance, visual, neuropsychological and blood biomarkers testing. In addition, they received different types of MRI scans aimed at investigating volume, structure and function of the brain.

IRP researchers identify brain connections associated with ADHD in youth

Large study finds atypical interactions between the frontal cortex and information processing centers deep in the brain

Researchers at the National Institutes of Health (NIH) have discovered that symptoms of attention-deficit/hyperactivity disorder (ADHD) are tied to atypical interactions between the brain’s frontal cortex and information processing centers deep in the brain. The researchers examined more than 10,000 functional brain images of youth with ADHD and published their results in the American Journal of Psychiatry. The study was led by researchers at NIH’s National Institute of Mental Health (NIMH) and National Human Genome Research Institute (NHGRI).

Luke Norman, Ph.D., a staff scientist in the NIMH Office of the Clinical Director, and colleagues analyzed brain images supplied by more than 8,000 youth with and without ADHD sourced from six different functional imaging datasets. Using these images, the researchers examined associations between functional brain connectivity and ADHD symptoms.

They found that youth with ADHD had heightened connectivity between structures deep in the brain involved in learning, movement, reward, and emotion (caudate, putamen, and nucleus accumbens seeds) and structures in the frontal area of the brain involved in attention and control of unwanted behaviors (superior temporal gyri, insula, inferior parietal lobe, and inferior frontal gyri).

IRP scientists find weak points on Epstein-Barr virus

New details of EBV protein could aid treatment, prevention efforts

Studies of interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein have uncovered targets that could be exploited in designing treatments and vaccines for this extremely common virus. The research was led by Jeffrey I. Cohen, M.D., and colleagues from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Study findings were published in the journal Immunity.

Approximately 95% of the world’s population is infected with EBV, which remains in the body permanently, typically in B lymphocytes, which are antibody-producing immune system cells, and cells lining the throat and pharynx. EBV can sometimes lead to B-cell cancers, including Burkitt, Hodgkin and non-Hodgkin lymphomas, or to gastric or nasopharyngeal cancers. Recently, EBV infection was shown to significantly raise the risk of developing multiple sclerosis. There is no vaccine to prevent EBV infection nor a specific treatment.

In this study, NIAID investigators examined a viral protein called gp42, which the virus must use to infect B cells. Theoretically, a vaccine or antibody-based treatment capable of blocking gp42’s ability to bind to or fuse with B cells would prevent EBV infection and, thus, the virus’s ability to persist in those cells. The team generated two gp42-specific mAbs, A10 and 4C12, and used X-ray crystallography to visualize how they interacted with gp42. The crystal structures revealed that the two mAbs interacted with distinct, non-overlapping sites on gp42. Monoclonal antibody A10 blocked the site on gp42 required for receptor binding, while 4C12 interfered with a different site that is involved in membrane fusion.

An electron micrograph showing three Epstein-Barr virus (EBV) particles colorized pink

An electron micrograph showing three Epstein-Barr virus (EBV) particles colorized pink.

For childhood cancer survivors, inherited genetic factors influence risk of cancers later in life

NIH-led study sheds light on the causes of new cancers among childhood cancer survivors and could have implications for their screening and follow-up

Common inherited genetic factors that predict cancer risk in the general population may also predict elevated risk of new cancers among childhood cancer survivors, according to a study led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health. The findings, published in Nature Medicine, provide additional evidence that genetics may play an important role in the development of subsequent cancers in survivors of childhood cancer and suggest that common inherited variants could potentially inform screening and long-term follow-up of those at greatest risk.

Childhood cancer survivors are known to have a higher risk of developing a new cancer later in life due to adverse effects of cancer treatment or rare inherited genetic factors. In the new study, the researchers evaluated the combined effect of common variants with history of radiation treatment and found the resulting elevated cancer risk was greater than the sum of the individual associations for treatment and genetic factors alone.

“Knowledge about a person’s genetic makeup could potentially be useful in managing their risk of subsequent cancers,” said lead investigator Todd M. Gibson, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics. “The hope would be that, in the future, we can incorporate genetics along with treatment exposures and other risk factors to provide a more complete picture of a survivor’s risk of subsequent cancers to help guide their long-term follow-up care.”

New antibodies target “dark side” of influenza virus protein

NIH researchers explore hidden, vulnerable region of influenza neuraminidase

Researchers at the National Institutes of Health have identified antibodies targeting a hard-to-spot region of the influenza virus, shedding light on the relatively unexplored “dark side” of the neuraminidase (NA) protein head. The antibodies target a region of the NA protein that is common among many influenza viruses, including H3N2 subtype viruses, and could be a new target for countermeasures. The research, led by scientists at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center, part of NIH, was published today in Immunity.

Influenza, or flu, sickens millions of people across the globe each year and can lead to severe illness and death. While vaccination against influenza reduces the burden of the disease, updated vaccines are needed each season to provide protection against the many strains and subtypes of the rapidly evolving virus. Vaccines that provide protection against a broad range of influenza viruses could prevent outbreaks of new and reemerging flu viruses without the need for yearly vaccine reformulation or vaccinations.

One way to improve influenza vaccines and other countermeasures is to identify new targets on the virus’s surface proteins in “conserved” regions — portions that tend to be relatively unchanged between different strains of the virus. Influenza NA is a surface protein containing a globular head portion and a narrow stalk portion. The underside of the NA head contains a highly conserved region with targets for antibodies — known as epitopes — that make it vulnerable to antibody binding and inhibition of the virus, as well as not being impacted by mutations common in drug-resistant strains. This region is termed the “dark side” due to its partially hidden location and relatively unexplored characteristics.

IRP study offers new clues into the causes of post-infectious ME/CFS

In-depth study finds brain, immune, and metabolic abnormalities linked to debilitating chronic disease

In a detailed clinical study, researchers at the National Institutes of Health have found differences in the brains and immune systems of people with post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). They also found distinct differences between men and women with the disease. The findings were published in Nature Communications.

“People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS. Now researchers can test whether these findings apply to a larger patient group and move towards identifying treatments that target core drivers of the disease.”

A team of multidisciplinary researchers discovered how feelings of fatigue are processed in the brains of people with ME/CFS. Results from functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which may cause fatigue by disrupting the way the brain decides how to exert effort.

Researchers identify brain hub with key role in learned response to direct and indirect threats

NIH-supported study in mice could inform treatments of trauma- and stress-related psychiatric conditions

Scientists have identified an area within the brain’s frontal cortex that may coordinate an animal’s response to potentially traumatic situations. Understanding where and how neural circuits involving the frontal cortex regulate such functions, and how such circuits could malfunction, may provide insight about their role in trauma-related and stress-related psychiatric disorders in people. The study, led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), a part of the National Institutes of Health, was published in Nature.

“Experiencing traumatic events is often at the root of trauma-related and stress-related psychiatric conditions, including alcohol use disorder (AUD),” said the study’s senior author, Andrew Holmes, Ph.D., senior investigator in NIAAA’s Laboratory of Behavioral and Genomic Neuroscience. “Additionally, witnessing others experience traumatic events can also contribute to these disorders.”

In animal models of stress and trauma, learning about potential sources of threat by observing how others deal with danger can be an effective way to avoid harm. Understanding the differences in how the brain processes direct experience of a threat compared to observing another’s response to a threat may shed light on factors that predispose humans to trauma- and stress-related psychiatric disorders.

Diagram of mouse prefrontal cortex showing neural projections to the midbrain (purple) and the amygdala (green), pathways involved in learning about threat

Diagram of mouse prefrontal cortex showing neural projections to the midbrain (purple) and the amygdala (green), pathways involved in learning about threat.

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This page was last updated on Wednesday, May 11, 2022