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:
NIH researchers found widespread differences in the brains of children with anxiety disorders that improved after treatment
Researchers at the National Institutes of Health have found overactivation in many brain regions, including the frontal and parietal lobes and the amygdala, in unmedicated children with anxiety disorders. They also showed that treatment with cognitive behavioral therapy (CBT) led to improvements in clinical symptoms and brain functioning. The findings illuminate the brain mechanisms underlying the acute effects of CBT to treat one of the most common mental disorders. The study, published in the American Journal of Psychiatry, was led by researchers at NIH’s National Institute of Mental Health (NIMH).
“The findings can help our understanding of how and for which children CBT works, a critical first step in personalizing anxiety care and improving clinical outcomes,” said senior author Melissa Brotman, Ph.D., Chief of the Neuroscience and Novel Therapeutics Unit in the NIMH Intramural Research Program.
Sixty-nine unmedicated children diagnosed with an anxiety disorder underwent 12 weeks of CBT following an established protocol. CBT, which involves changing dysfunctional thoughts and behaviors through gradual exposure to anxiety-provoking stimuli, is the current gold standard for treating anxiety disorders in children.
Three different HIV antibodies each independently protected monkeys from acquiring simian-HIV (SHIV) in a placebo-controlled proof-of-concept study intended to inform development of a preventive HIV vaccine for people. The antibodies — a human broadly neutralizing antibody and two antibodies isolated from previously vaccinated monkeys — target the fusion peptide, a site on an HIV surface protein that helps the virus fuse with and enter cells. The study, published in Science Translational Medicine, was led by the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Antibodies that target the fusion peptide can neutralize diverse strains of HIV in vitro, that is, in a test tube or culture dish outside of a living organism. The NIAID VRC isolated a fusion peptide-directed human antibody, called VRC34.01, from a person living with HIV who donated blood samples for research. They also isolated two antibodies from rhesus macaques — a species of monkey with immune systems like humans’ — who previously had received a vaccine regimen designed to generate fusion peptide-directed antibodies. Demonstrating that these antibodies protect animals would validate the fusion peptide as a target for human vaccine design. SHIV challenge—administering an infective dose of SHIV — to rhesus macaques is a widely used animal model for assessing the performance of HIV antibodies and vaccines.
In this study, rhesus macaques in each of four groups received a single intravenous infusion of one type of antibody — a 2.5 or 10 mg/kg of bodyweight dose of VRC34.01, or one of the two vaccine-elicited rhesus macaque antibodies — and other monkeys received a placebo infusion. To determine the protective effect of the antibodies, each monkey was challenged five days after infusion with a strain of SHIV known to be sensitive to fusion peptide-directed antibodies.
Transmission electron micrograph of HIV-1 virus particles (red) budding and replicating from a segment of a chronically infected H9 cell (blue).
An atlas revealing the activity of individual placental cells during childbirth offers insight on what happens at the maternal-fetal interface during term labor, according to a study supported by the National Institutes of Health (NIH). The atlas provides a single-cell analysis of the human placenta and its surrounding membranes and is the first to use this method to understand the communication that occurs between maternal and fetal cells during the process of labor. Studying these processes aids understanding of typical labor and delivery at term, as well as preterm labor and delivery, which occurs before 37 weeks of pregnancy and is a leading cause of infant death and long-term disability. The work, led by researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), is published in the latest issue of Science Translational Medicine.
The study team created the placental atlas by using single-cell RNA sequencing (also called single-cell transcriptomics), which examines the activity and signaling patterns of individual cells. The atlas, which is based on samples from 42 term pregnancies, describes changes in gene expression patterns among the different cell types in the placenta and its surrounding membranes, which include both maternal and fetal-derived cells.
The researchers found that cells most affected by labor were in the chorioamniotic membranes, which surround the fetus and rupture as part of the labor and delivery process. They also found that fetal stromal and maternal decidual cells were particularly active in generating inflammatory signaling. These findings are consistent with previous research showing that inflammation (unrelated to infection) is important for sustaining labor.
NIH-supported findings suggest the need to expand definitions of addiction treatment success beyond abstinence
Reducing stimulant use was associated with significant improvement in measures of health and recovery among people with stimulant use disorder, even if they did not achieve total abstinence. This finding is according to an analysis(link is external) of data from 13 randomized clinical trials of treatments for stimulant use disorders involving methamphetamine and cocaine. Historically, total abstinence has been the standard goal of treatment for substance use disorders, however, these findings support the growing recognition that a more nuanced perspective on measuring treatment success may be beneficial.
The study, published in Addiction, was led by scientists at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in collaboration with researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.
Researchers found that transitioning from high use (five or more days a month) to lower use (one to four days a month) was associated with lower levels of drug craving, depression, and other drug-related challenges compared to no change in use. These results suggest that reduction in use of methamphetamine or cocaine, in addition to abstinence, is a meaningful surrogate or intermediate clinical outcome in medication development for stimulant addiction. Unlike other substance use disorders, such as opioid use disorder or alcohol use disorder, there are currently no U.S. Food and Drug Administration-approved pharmacological treatments for stimulant use disorders.
“These findings align with an evolving understanding in the field of addiction, affirming that abstinence should be neither the sole aim nor only valid outcome of treatment,” said NIDA Director Nora Volkow, M.D. “Embracing measures of success in addiction treatment beyond abstinence supports more individualized approaches to recovery, and may lead to the approval of a wider range of medications that can improve the lives of people with substance use disorders.”
Researchers at the National Institutes of Health have published an atlas of zebrafish development, detailing the gene expression programs that are activated within nearly every cell type during the first five days of development, a period in which embryos mature from a single cell into distinct cell types. These diverse cells become tissues and organs that form juvenile fish capable of swimming and looking for food. The findings are published in Developmental Cell.
“Perhaps surprisingly, tiny zebrafish provide us with significant insight into human development and disease. Many of the gene expression programs that direct embryonic growth are similar across fish, people, and other animals,” said Christopher McBain, Ph.D., scientific director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which conducted the work. “Since zebrafish are visibly transparent, fertilize eggs externally, and are easy to study genetically, they represent a unique and effective way to model human disease.”
The process of embryonic development is orchestrated by instructions in DNA that direct different programs of gene expression within individual cells, which give different cell types their unique functional characteristics. To create the atlas, the study team used a method called single-cell RNA sequencing to identify gene expression programs over the course of five days, with samples taken every two to 12 hours. The resulting atlas follows nearly 490,000 cells continuously over 120 hours after fertilization, with an average of 8,621 transcripts and 1,745 genes detected per cell. The study team then sorted these data among known cell types and cell states during development.
BEST4+ cells are labelled red along the zebrafish gastrointestinal tract. These understudied cells are linked to gastrointestinal diseases and cancer in people.
W. Kimryn Rathmell, M.D., Ph.D., began work today as the 17th director of the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). A renowned kidney cancer expert and influential leader in cancer research and patient care, Dr. Rathmell was selected by President Biden to succeed Monica M. Bertagnolli, M.D., who left NCI to become the NIH director on November 9.
“I want to officially welcome Dr. Rathmell to the National Cancer Institute on her first day as director,” said Department of Health and Human Services Secretary Xavier Becerra. “Dr. Rathmell begins her new role at an important time. The President and First Lady reignited the Biden Cancer Moonshot℠ to dramatically accelerate progress in the fight against cancer—and NCI is helping to lead the charge. Dr. Rathmell brings decades of experience helping to advance research and drive innovation to improve care for patients. She joins an extraordinary team already doing great work to prevent, detect, and treat cancer to make sure Americans are living longer, healthier lives. I look forward to working closely with Dr. Rathmell in the months and years ahead to help end cancer as we know it.”
“I am thrilled to welcome Dr. Rathmell to NIH, and I know she is the right leader at the right time for NCI,” said Dr. Bertagnolli. “She is a fantastic combination of researcher and clinician who deeply understands the process of translating lab research into effective cancer treatments. NCI is in great hands to actualize the brighter future we all want for people with cancer.”
Study suggests greater CD8+ T-cell activity may increase HIV immunity
An effective HIV vaccine may need to prompt strong responses from immune cells called CD8+ T cells to protect people from acquiring HIV, according to a new study from researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and colleagues. The study findings, appearing in Science, draw comparisons between the immune system activity of past HIV vaccine study participants and people with HIV who naturally keep the virus from replicating even in the absence of antiretroviral therapy (ART). The latter individuals are often called “long-term non-progressors” or “elite controllers” (LTNPs/ECs).
When HIV enters the body, the virus begins to damage the immune system by inserting itself into CD4+ T cells, which are white blood cells that help coordinate the immune response to pathogens. In most people, HIV continues to replicate and damage more and more CD4+ T cells unless controlled by ART. Among LTNPs/ECs, the immune system appears to promptly recognize CD4+ cells with HIV and activate other immune cells called CD8+ T cells. CD8+ T cells destroy CD4+ cells with HIV, enabling the suppression of HIV in a person’s blood.
The aim of an effective HIV vaccine is to provide durable protective immunity to HIV, or if initial defenses are bypassed, to help control HIV in the body long term, as happens with LTNPs/ECs. Although several preventive HIV vaccine candidates have been designed to stimulate CD8+ T-cell activity, they did not prevent HIV acquisition or control viral replication in clinical trials. Understanding and addressing this lack of effect is a scientific priority of HIV vaccine research.
Scientists in the HIV-Specific Immunity Section of NIAID’s Laboratory of Immunoregulation and colleagues designed their study to better understand which CD8+ T-cell functions were lacking in previous HIV vaccine recipients. They compared laboratory samples from previous HIV vaccine study participants with samples from LTNPs/ECs. They found that both HIV vaccine recipients and LTNPs/ECs generated large numbers of CD8+ T cells that recognized HIV. However, unlike the CD8+ T cells of LTNPs/ECs, HIV vaccine recipients’ CD8+ T cells failed to deliver the proteins necessary to destroy HIV-infected CD4+ T cells with HIV.
Layout featuring colorized 3D prints of HIV virus particles (pink with teal surface proteins) and a background image that is a colorized transmission electron micrograph of HIV virus particles (pink) budding and replicating from an H9 T cell (purple). Micrograph captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Note: not to scale.
Genome topology map of human retina development lays foundation for understanding diverse clinical phenotypes in simple and complex eye diseases
Researchers at the National Institutes of Health have mapped the 3D organization of genetic material of key developmental stages of human retinal formation, using intricate models of a retina grown in the lab. The findings lay a foundation for understanding clinical traits in many eye diseases, and reveal a highly dynamic process by which the architecture of chromatin, the DNA and proteins that form chromosomes, regulates gene expression. The findings were published in Cell Reports.
“These results provide insights into the heritable genetic landscape of the developing human retina, especially for the most abundant cell types that are commonly associated with vision impairment in retinal diseases,” said the study’s lead investigator, Anand Swaroop, Ph.D., chief of the Neurobiology, Neurodegeneration, and Repair Laboratory at the National Eye Institute (NEI), part of NIH.
Using deep Hi-C sequencing, a tool used for studying 3D genome organization, the researchers created a high-resolution map of chromatin in a human retinal organoid at five key points in development. Organoids are tissue models grown in a lab and engineered to replicate the function and biology of a specific type of tissue in a living body.
This image metaphorically captures the cell differentiation process during retinal organoid development. Loose yarn representing uncompacted DNA is wound by a crochet hook around buttons representing nucleosomes and culminating in a tightly condensed ball of chromatin that forms an eye-like shape.
Among those aged 35 to 44, overdose mortality more than tripled during this period, NIH study reports
Drug overdose deaths rose markedly between January to June 2018 and July to December 2021 among 10- to 44-year-old girls and women who were pregnant or pregnant within the previous 12 months, according to a new study by researchers at National Institute on Drug Abuse (NIDA) at the National Institutes of Health. Overdose mortality more than tripled among those aged 35 to 44 during the study period, from 4.9 deaths per 100,000 mothers aged 35 to 44 with a live birth in the 2018 period to 15.8 in the 2021 period. Over 60% of these pregnancy-associated overdose deaths occurred outside healthcare settings, though often in counties with available healthcare resources, such as emergency and obstetric care. Published today in JAMA Psychiatry, the findings suggest that, while treatment is available to pregnant women with substance use disorders, significant barriers — such as penalization, stigma, discrimination, and limited socioeconomic resources — may obstruct the path to care, the authors note.
“The stigma and punitive policies that burden pregnant women with substance use disorder increase overdose risk by making it harder to access life-saving treatment and resources,” said Nora Volkow, M.D., NIDA Director and senior author on the study. “Reducing barriers and the stigma that surrounds addiction can open the door for pregnant individuals to seek and receive evidence-based treatment and social support to sustain their health as well as their child’s health.”
Monica M. Bertagnolli, M.D., started today as the 17th director of the National Institutes of Health, the nation’s biomedical research agency and largest public funder of biomedical research in the world. She is the first surgeon and the second woman to hold the position. Nominated by President Biden, Dr. Bertagnolli was confirmed on a bipartisan basis by the U.S. Senate on November 7. She transitioned from her role as the 16th director of the National Cancer Institute, a position she has held since October 2022. NCI Principal Deputy Director Douglas R. Lowy, M.D., will serve as the NCI acting director until President Biden appoints a new director.
In his nomination announcement earlier this year, President Biden stated: “Dr. Bertagnolli has spent her career pioneering scientific discovery and pushing the boundaries of what is possible to improve cancer prevention and treatment for patients and ensuring that patients in every community have access to quality care. Dr. Bertagnolli is a world-class physician-scientist whose vision and leadership will ensure NIH continues to be an engine of innovation to improve the health of the American people.”
Growing up in rural Wyoming, Dr. Bertagnolli experienced and saw firsthand the challenges faced by rural communities to access medical care and participate in medical research. Due to that lived experience, equity is a core value that drives all her efforts, which includes ensuring NIH research is equitable and accessible to all people from all walks of life regardless of income or zip code.
“As a physician-scientist for more than 30 years, I have seen the transformative power of NIH research to produce results that save lives, including my own treatment for breast cancer,” said Dr. Bertagnolli. “As NIH director, I look forward to ensuring that NIH continues to be the steward of our nation’s medical research while engaging all people and communities in the research effort that includes informing medical practice that drives equitable access to health care for all.”
