anxiety – NIH Director's Blog (original) (raw)

Mapping Psilocybin’s Brain Effects to Explore Potential for Treating Mental Health Disorders

Posted on August 15th, 2024 by Dr. Monica M. Bertagnolli

Credit: Donny Bliss/NIH

Psilocybin is a natural ingredient found in “magic mushrooms.” A single dose of this psychedelic can distort a person’s perception of time and space, as well as their sense of self, for hours. It can also trigger strong emotions, ranging from euphoria to fear. While psilocybin comes with health risks and isn’t recommended for recreational use, there’s growing evidence that—under the right conditions—its effects on the brain might be harnessed in the future to help treat substance use disorders or mental illnesses.

To explore this potential, it will be important to understand how psilocybin exerts its effects on the human brain. Now, a study in Nature supported in part by NIH has taken a step in this direction, using functional brain mapping in healthy adults before, during, and after taking psilocybin to visualize its impact. While earlier studies in animals suggested that psilocybin makes key brain areas more adaptable or “plastic,” this new research aims to clarify changes in the function of larger brain networks and their connection to the experiences people have with this psychedelic drug.

In the study, the team led by Joshua Siegel, Nico Dosenbach and Ginger Nicol, Washington University School of Medicine in St. Louis, recruited seven healthy adults to take, in separate sessions, a high dose of psilocybin and the stimulant methylphenidate, the generic form of Ritalin, under controlled conditions. Because taking psilocybin comes with a risk for having disturbing or negative experiences, a pair of trained experts stayed with each participant throughout the sessions to provide guidance and support. They also helped participants prepare for and process the experience afterwards.

To visually capture the impact of psilocybin on the brain, the researchers had each participant undergo an average of 18 functional MRI brain scan visits. Four of the study’s participants also returned six to 12 months later to take an additional psilocybin dose. Comparisons of the brain images revealed profound and widespread, but temporary, changes to the brain’s functional networks. While an individual’s functional brain network is typically as distinctive as a fingerprint, psilocybin made the participants’ brain networks look so similar in the scans that the researchers couldn’t tell them apart. In addition, by following the brain scans with specialized questionnaires given to elicit details about participants’ subjective experiences with psilocybin, the researchers were able to generate precise data on each person’s unique impressions and associated changes in their brain networks.

For all the participants, psilocybin desynchronized the brain’s default mode network, an interconnected set of brain areas that are most active when people are daydreaming or otherwise not engaged in any focused, goal-directed mental activity. By comparison, the default mode network remained stable after study participants took methylphenidate. Once the effects of psilocybin wore off, brain function returned almost to its original state. However, the researchers did note small but potentially important differences in each participant’s brain scans after taking psilocybin that remained for weeks.

The researchers suggest that the short-term changes in the default mode network likely explain psilocybin’s psychedelic effects, including the way it changes the way a person thinks about themselves in relation to other people and the world. They also suggest that the more subtle, longer-term effects they observed might indicate that the brain is more flexible in the weeks following a dose of psilocybin in ways that could allow for a healthier state. This may help explain preliminary research showing that psilocybin may have benefits for treating substance use disorders, as well as depression, anxiety, and other mental health conditions.

Though these findings are encouraging, they should not be seen as a reason to try psilocybin without clinician supervision or use it to self-medicate. The drug is not proven or approved as a treatment for any condition, and its unsupervised use comes with serious risks. The researchers hope that with much more clinical study of how and why this drug affects individuals in the powerful ways that it does, this kind of research may one day lead to a greater understanding of the human brain and promising new interventions that improve mental health.

Reference:

Siegel JS, et al. Psilocybin desynchronizes the human brain. Nature. DOI: 10.1038/s41586-024-07624-5 (2024).

NIH Support: National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke

Posted In: Health, Science

Tags: anxiety, brain, default mode network, depression, imaging, mental health disorders, neuroscience, psilocybin, psychedelic, substance use disorders

Diagnosis and Treatment of Mental Health Conditions During and After Pregnancy is On the Rise, But Disparities Still Exist

Posted on April 18th, 2024 by Dr. Monica M. Bertagnolli

Credit: Marco/Adobe Stock

Pregnancy and childbirth are often thought of as joyful times. Yet, we know that mental health conditions including perinatal depression, anxiety, and post-traumatic stress disorder (PTSD) are common complications during and after pregnancy, and this is contributing to a maternal health crisis in this country.

Now, a trio of NIH-supported studies reported in the journal Health Affairs show that diagnosis and treatment of mental health conditions such as anxiety, depression, and PTSD during pregnancy and in the first year after giving birth rose significantly in Americans with private health insurance from 2008 to 2020.1,2,3 While these are encouraging signs of increasing mental health awareness and service use, these studies also showed that this increase hasn’t happened equally across all demographic groups and states, making it clear there’s more work to do to ensure that people from all walks of life have access to the care they need, regardless of their race, ethnicity, geographic location, financial status, or other factors.

The findings come from a research team including Kara Zivin and Stephanie Hall and their colleagues at the University of Michigan, Ann Arbor. They recognized a worrying crisis in maternal mental illness in the U.S., with serious health risks and many potential long-term negative impacts for new parents and their infants. While earlier studies had looked at the prevalence of mental health conditions in the perinatal period, Zivin and Hall wanted to explore nationwide trends in the diagnosis of PTSD and what they refer to as perinatal mood and anxiety disorders (PMAD) among people giving birth between ages 15 and 44.

In the first study, using a database of administrative medical claims representing insured people across the U.S., the researchers examined PMAD diagnoses (including depressive and anxiety disorders) among those with private health insurance and found that the diagnosis rate had increased by more than 93% over the 12-year period under study. The rates also showed a sharp uptick after 2015, after the Affordable Care Act (ACA) went into effect in 2014. By 2020, 28% of those who were pregnant or in their postpartum period received a diagnosis of PMAD.

The researchers found that rate of suicidality (that is, suicidal ideation or diagnoses of self-harm) among people during pregnancy and just after childbirth more than doubled over the same period, although that rate dipped among those who had received a PMAD diagnosis. The rate at which individuals who were pregnant or in their postpartum period received any form of talk therapy covered by their private insurance increased by 16% from 2008 to 2020.

The second report focused specifically on PTSD diagnoses among privately insured people over the same period. The data show a near quadrupling of PTSD diagnoses in the months surrounding childbirth, with diagnoses in nearly 2% of privately insured people by 2020. Most of the increase in PTSD diagnoses occurred in people who had already been diagnosed with PMAD.

In the third study, the researchers wanted to learn if there were increases in antidepressant prescriptions for those diagnosed with PMAD, especially after new guidelines from several professional organizations were issued in 2015 and 2016. The findings show a decrease of 3% per year from 2008 to 2016, followed by a 32% increase in 2017, with prescription rates continuing to climb each year through 2020. By 2020, slightly less than half of those diagnosed with PMAD received a prescription for an antidepressant, suggesting that the clinical recommendations made a difference in clinical practice. However, there are signs of racial disparities, with White people with PMAD diagnoses receiving antidepressants more often than people in other racial groups.

In fact, all three studies show differences between people in different age, race, ethnicity, and geographic groups. For example, White people were more likely to be diagnosed with PTSD during the perinatal period, followed by Black people. By comparison, people of unknown race, as well as people who identified as Hispanic and Asian, were diagnosed less often. At the same time, the largest increase in PMAD diagnoses among races and ethnicities was among Black people, increasing from 14% of deliveries in 2008 to 22% in 2020.

Looking at age groups, the initial prevalence of PMAD diagnoses was highest among people aged 40 to 44, yet the youngest people (aged 15 to 24) experienced the largest increase in diagnoses. The youngest age group also had the largest increases in antidepressant prescriptions, and those aged 15 to 26 were more likely to be diagnosed with PTSD than those in older age groups. The first study also showed wide variation between states in the rate of PMAD diagnoses before and after implementation of the ACA.

The findings suggest there have been improvements in doctors’ recognition and treatment of PMAD and PTSD in the months surrounding childbirth. Increases in health insurance coverage and laws requiring equal treatment of mental health conditions may also be playing a role, along with greater social awareness and acceptance of mental health conditions generally. The researchers noted, however, that the findings don’t represent people with government-funded health insurance or those who lack health insurance completely.

It will be important to learn in future studies more about those who may still not be receiving the mental health care they need. The researchers report plans to look deeper into changes that have taken place at the state level and the impact of the pandemic and the rise of telehealth since 2020. Other recent NIH-supported research suggests that relatively straightforward interventions to reduce postpartum anxiety and depression can be remarkably effective. The key step will be not only identifying interventions that work, but also figuring out how to deliver effective treatments to the people who need them.

References:

[1] Zivin K, et al. Perinatal Mood and Anxiety Disorders Rose Among Privately Insured People, 2008-20. Health Affairs. DOI: 10.1377/hlthaff.2023.01437 (2024).

[2] Hall SV, et al. Perinatal Posttraumatic Stress Disorder Diagnoses Among Commercially Insured People Increased, 2008-20. Health Affairs. DOI: 10.1377/hlthaff.2023.01447 (2024).

[3] Hall SV, et al. Antidepressant Prescriptions Increased for Privately Insured People With Perinatal Mood And Anxiety Disorder, 2008-20. Health Affairs. DOI: 10.1377/hlthaff.2023.01448 (2024).

NIH Support: National Institute of Mental Health, National Institute on Minority Health and Health Disparities

Using AI to Advance Understanding of Long COVID Syndrome

Posted on June 7th, 2022 by Lawrence Tabak, D.D.S., Ph.D.

The COVID-19 pandemic continues to present considerable public health challenges in the United States and around the globe. One of the most puzzling is why many people who get over an initial and often relatively mild COVID illness later develop new and potentially debilitating symptoms. These symptoms run the gamut including fatigue, shortness of breath, brain fog, anxiety, and gastrointestinal trouble.

People understandably want answers to help them manage this complex condition referred to as Long COVID syndrome. But because Long COVID is so variable from person to person, it’s extremely difficult to work backwards and determine what these people had in common that might have made them susceptible to Long COVID. The variability also makes it difficult to identify all those who have Long COVID, whether they realize it or not. But a recent study, published in the journal Lancet Digital Health, shows that a well-trained computer and its artificial intelligence can help.

Researchers found that computers, after scanning thousands of electronic health records (EHRs) from people with Long COVID, could reliably make the call. The results, though still preliminary and in need of further validation, point the way to developing a fast, easy-to-use computer algorithm to help determine whether a person with a positive COVID test is likely to battle Long COVID.

In this groundbreaking study, NIH-supported researchers led by Emily Pfaff, University of North Carolina, Chapel Hill, and Melissa Haendel, the University of Colorado Anschutz Medical Campus, Aurora, relied on machine learning. In machine learning, a computer sifts through vast amounts of data to look for patterns. One reason machine learning is so powerful is that it doesn’t require humans to tell the computer which features it should look for. As such, machine learning can pick up on subtle patterns that people would otherwise miss.

In this case, Pfaff, Haendel, and team decided to “train” their computer on EHRs from people who had reported a COVID-19 infection. (The records are de-identified to protect patient privacy.) The researchers found just what they needed in the National COVID Cohort Collaborative (N3C), a national, publicly available data resource sponsored by NIH’s National Center for Advancing Translational Sciences. It is part of NIH’s Researching COVID to Enhance Recovery (RECOVER) initiative, which aims to improve understanding of Long COVID.

The researchers defined a group of more than 1.5 million adults in N3C who either had been diagnosed with COVID-19 or had a record of a positive COVID-19 test at least 90 days prior. Next, they examined common features, including any doctor visits, diagnoses, or medications, from the group’s roughly 100,000 adults.

They fed that EHR data into a computer, along with health information from almost 600 patients who’d been seen at a Long COVID clinic. They developed three machine learning models: one to identify potential long COVID patients across the whole dataset and two others that focused separately on people who had or hadn’t been hospitalized.

All three models proved effective for identifying people with potential Long-COVID. Each of the models had an 85 percent or better discrimination threshold, indicating they are highly accurate. That’s important because, once researchers can identify those with Long COVID in a large database of people such as N3C, they can begin to ask and answer many critical questions about any differences in an individual’s risk factors or treatment that might explain why some get Long COVID and others don’t.

This new study is also an excellent example of N3C’s goal to assemble data from EHRs that enable researchers around the world to get rapid answers and seek effective interventions for COVID-19, including its long-term health effects. It’s also made important progress toward the urgent goal of the RECOVER initiative to identify people with or at risk for Long COVID who may be eligible to participate in clinical trials of promising new treatment approaches.

Long COVID remains a puzzling public health challenge. Another recent NIH study published in the journal Annals of Internal Medicine set out to identify people with symptoms of Long COVID, most of whom had recovered from mild-to-moderate COVID-19 [2]. More than half had signs of Long COVID. But, despite extensive testing, the NIH researchers were unable to pinpoint any underlying cause of the Long COVID symptoms in most cases.

So if you’d like to help researchers solve this puzzle, RECOVER is now enrolling adults and kids—including those who have and have not had COVID—at more than 80 study sites around the country.

References:

[1] Identifying who has long COVID in the USA: a machine learning approach using N3C data. Pfaff ER, Girvin AT, Bennett TD, Bhatia A, Brooks IM, Deer RR, Dekermanjian JP, Jolley SE, Kahn MG, Kostka K, McMurry JA, Moffitt R, Walden A, Chute CG, Haendel MA; N3C Consortium. Lancet Digit Health. 2022 May 16:S2589-7500(22)00048-6.

[2] A longitudinal study of COVID-19 sequelae and immunity: baseline findings. Sneller MC, Liang CJ, Marques AR, Chung JY, Shanbhag SM, Fontana JR, Raza H, Okeke O, Dewar RL, Higgins BP, Tolstenko K, Kwan RW, Gittens KR, Seamon CA, McCormack G, Shaw JS, Okpali GM, Law M, Trihemasava K, Kennedy BD, Shi V, Justement JS, Buckner CM, Blazkova J, Moir S, Chun TW, Lane HC. Ann Intern Med. 2022 May 24:M21-4905.

Links:

COVID-19 Research (NIH)

National COVID Cohort Collaborative (N3C) (National Center for Advancing Translational Sciences/NIH)

RECOVER Initiative

Emily Pfaff (University of North Carolina, Chapel Hill)

Melissa Haendel (University of Colorado, Aurora)

NIH Support: National Center for Advancing Translational Sciences; National Institute of General Medical Sciences; National Institute of Allergy and Infectious Diseases

Posted In: News

Tags: AI, anxiety, artificial intelligence, brain fog, COVID-19, EHR, electronic health records, fatigue, long COVID, Long COVID syndrome, machine learning, N3C, National COVID Cohort Collaborative, novel coronavirus, pandemic, PASC, post-acute sequelae of COVID-19, RECOVER Initiative, Researching COVID to Enhance Recovery, SARS-CoV-2

U.S. Surgeon General on Emotional Well-Being and Fighting the Opioid Epidemic

Posted on June 10th, 2021 by Dr. Francis Collins

From September 2019 to September 2020, the Centers for Disease Control and Prevention reported nearly 90,000 overdose deaths in the United States. These latest data on the nation’s opioid crisis offer another stark reminder that help is desperately needed in communities across the land. NIH’s research efforts to address the opioid crisis have been stressed during the pandemic, but creative investigators have come up with workarounds like wider use of telemedicine to fill the gap.

Much of NIH’s work on the opioid crisis is supported by the Helping to End Addiction Long-term (HEAL) Initiative. Recently, the more-than 500 investigators supported by HEAL came together virtually for their second annual meeting to discuss the initiative’s latest research progress and challenges.

As part of the meeting, I had a conversation with Dr. Vivek Murthy, the U.S. Surgeon General. Dr. Murthy served as the 19th U.S. Surgeon General under the Obama Administration and was recently confirmed as the 21st Surgeon General under the Biden Administration. In his first term as America’s Doctor, in which I had the privilege of working with him, Dr. Murthy created initiatives to tackle our country’s most urgent public health issues, including addiction and the opioid crisis. He also issued the nation’s first Surgeon General’s Report on addiction, presenting the latest scientific data and issuing a call to action to recognize addiction as a chronic illness—and not a moral failing.

In 2016, Dr. Murthy sent a letter to 2.3 million healthcare professionals urging them to join a movement to tackle the opioid epidemic. This was the first time in the history of the office that a Surgeon General had issued a letter calling the medical profession to action on this issue. In 2017, Dr. Murthy focused his attention on chronic stress and isolation as prevalent problems with profound implications for health, productivity, and happiness.

Our conversation during the HEAL meeting took place via videoconference, with the Surgeon General connecting from Washington, D.C., and me linking in from my home in Maryland. Here’s a condensed transcript of our chat:

Collins: Welcome, Dr. Murthy. We’ve known each other for a few years, and I know that you’ve talked extensively about the national epidemic of loneliness. What have you learned about loneliness and how it affects our emotional wellbeing?

Murthy: Thanks, Francis. Loneliness and perceived social isolation are profound challenges for communities struggling with addiction, including opioid use disorders. I had no real background in these issues when I started as Surgeon General in 2014. I was educated by people I met all across the country, who in their own way would tell me their stories of isolation and loneliness. It’s a common stressor, especially for those who struggle with opioid use disorders. Stress can be a trigger for relapse. It’s also connected with overdose attempts and overdose deaths.

But loneliness is bigger than addiction. It is not just a bad feeling. Loneliness increases our risk of anxiety and depression, dementia, cardiac disease, and a host of other conditions. However you cut it, addressing social isolation and loneliness is an important public-health issue if we care about addiction, if we care about mental health—if we care about the physical wellbeing of people in our country.

Collins: Vivek, you made the diagnosis of an epidemic of American loneliness back before COVID-19 came along. With the emergence of COVID-19 a little more than a year ago, it caused us to isolate ourselves even more. Now that you’re back as Surgeon General and seeing the consequences of the worst pandemic in 103 years, is loneliness even worse now than before the pandemic?

Murthy: I think there are many people for whom that sense of isolation and loneliness has increased during the pandemic. But the pandemic has been a very heterogenous experience. There are some people who have found themselves more surrounded by their extended family or a close set of friends. That has been, in many ways, a luxury. For many people who are on the frontlines as essential workers, whose jobs don’t permit them to just pick up and leave and visit extended family, these have been very stressful and isolating times.

So, I am worried. And I’m particularly worried about young people—adolescents and young adults. They already had high rates of depression, anxiety, and suicide before the pandemic, and they’re now struggling with loneliness. I mention this because young people are so hyperconnected by technology, they seem to be on TikTok and Instagram all the time. They seem to be chatting with their friends constantly, texting all the time. How could they feel isolated or lonely?

But one of the things that has become increasingly clear is what matters when it comes to loneliness is the quality of your human connections, not the quantity. For many young people that I spoke to while traveling across the country, they would say that, yes, we’re connected to people all the time. But we don’t necessarily feel like we can always be ourselves in our social media environment. That’s where comparison culture is at its height. That’s where we feel like our lives are always falling short, whether it’s not having a fancy enough job, not having as many friends, or not having the right clothing or other accessories.

We talk a lot about resilience in our country. But how do we develop more resilient people? One of the keys is to recognize that social connections are an important source of resilience. They are our natural buffers for stress. When hard things happen in our lives, so many of us just instinctively will pick up the phone to call a friend. Or we’ll get into the car and go visit a member of our family or church. The truth is, if we want to build a society that’s healthier mentally and physically, that is more resilient, and that is also more happy and fulfilled, we have to think about how we build a society that is more centered around human connection and around relationships.

My hope is that one of the things we will reevaluate is building a people-centered society. That means designing workplaces that allow people to prioritize relationships. It means designing schools that equip our children with social and emotional learning tools to build healthy relationships from the earliest ages. It means thinking about public policy, not from just the standpoint of financial impact but in terms of how it impacts communities and how it can fracture communities.

We have an opportunity to do that now, but it won’t happen by default. We have to think through this very proactively, and it starts with our own lives. What does it mean for each of us to live a truly people-centered life? What decisions would we make differently about work, about how we spend time, about where we put our attention and energy?

Collins: Those are profound and very personal words that I think we can all relate to. Let me ask you about another vulnerable population that we care deeply about. There are 50 million Americans who are living with chronic pain, invisible to many, especially during the pandemic, for whom being even more isolated has been particularly rough—and who are perhaps in a circumstance where getting access to medical care has been challenging. As Surgeon General, are you also looking closely at the folks with chronic pain?

Murthy: You’re right, the populations that were more vulnerable pre-pandemic have really struggled during this pandemic—whether that’s getting medications for treatment, needed counseling services, or taking part in social support groups, which are an essential part of the overall treatment approach and staying in recovery. It’s a reminder of how urgent it is for us, number one, to improve access to healthcare in our country. We’ve made huge strides in this area, but millions are still out of reach of the healthcare system.

A potential silver lining of this pandemic is telemedicine, which has extraordinary potential to improve and extend access to services for people living with substance use disorders. In 2016, I remember visiting a small Alaskan fishing village that you can only get to by boat or plane. In that tiny village of 150 people, I walked into the small cabin where they had first-aid supplies and provided some basic medical care. There I saw a small monitor mounted on the wall and a chair. They told me that the monitor is where people, if they’re dealing with a substance use disorder, come and sit to get counseling services from people in the lower 48 states. I was so struck by that. To know that telemedicine could reach this remote Alaskan village was really extraordinary.

I think the pandemic has accelerated our adoption of telemedicine by perhaps five years or more. But we must sustain this momentum not only with investment in broadband infrastructure, but with other things that seem mundane, like the reimbursement structure around telemedicine. I talk to clinicians now who say they are seeing some private insurers go back on reimbursement for telemedicine because the pandemic is starting to get better. But the lesson learned is not that telemedicine should go away; it’s that we should be integrating it even more deeply into the practice of medicine.

The future of care, I believe, is bringing care closer to where people are, integrating it into their workflow, bringing it to their homes and their neighborhoods. I saw this so clearly for many of the patients I cared for who fell into that category of being in vulnerable populations. They were working two, three jobs, trying to take care of their children at the same time. Having a conversation with them about how they could find time to go to the gym was almost a laughable matter because they were literally dealing with issues of survival and putting food on the table for their kids. As a society we have to do more to understand the lives of people who fall into those categories and provide services that bring what they need to them, as opposed to expecting them to come to us.

If we continue in a purely fee-for-service-based environment where people must go multiple places to get their care, we will not ultimately get care to the vulnerable populations that have struggled the most and that are hoping that we will do better this time around. I think we can. I think we must. And I think COVID may just be, in part, the impetus to move forward in a different way that we need.

Collins: Let’s talk a minute about the specifics of the opioid crisis. If we’re going to move this crisis in the right direction, are there particular areas that you would say we really need more rigorous data in order to convince the medical care system—both the practitioners and the people deciding about reimbursement—that these are things we must do?

Murthy: There are a few areas that come to mind, and I’ve jotted them down. It is so important for us to do research with vulnerable populations, recognizing they often get left out. It’s essential that we conduct studies specifically for these populations so that we can better target interventions to them.

The second area is prevention programs. People want to prevent illnesses. I have not met anybody anywhere in the United States who has said, “I’d rather get diabetes first and treat it versus prevent it in the first place.” As silly as that might sound, it is the exact opposite of how we finance health interventions in our country. We put the lion’s share of our dollars in treatment. We do very little in prevention.

The third piece is the barriers faced by primary-care clinicians, who we want to be at the heart of providing a lot of these treatment services. I’ll tell you, just from my conversations with primary-care docs around the country, they worry about not having enough for their patients in the way of social work and social support services in their offices.
Finally, it has become extraordinarily clear to me that social support is one of the critical elements of treatment for substance use disorders. That it is what helps keep people in recovery. I think about the fact that many people I met who struggle with opioid use disorders had family members who were wondering how they could be helpful. They weren’t sure. They said, “Should I just keep badgering my relative to go to treatment? Should I take a tough love approach? What should I do to be helpful?”

This actually is one of the most pressing issues: social support is most often going to come from family, from friends, and from other community members. So, being able to guide them in an evidence-based way about what measures, what forms actually can be helpful to people struggling with opioid use disorders could also be immensely helpful to a group that is looking to provide assistance and support, but often is struggling to figure out how best to do that.

Collins: Vivek, you were focused as Surgeon General in the Obama Administration on the importance of changing how America thinks about addiction—that it is not a moral failing but a chronic illness that has to be treated with compassion, urgency, skill, and medical intervention. Are we getting anywhere with making that case?

Murthy: Sometimes people shy away from addressing the stigma around addiction because it feels too hard to address. But it is one of the most important issues to address. If people are still feeling judged for their disorders, they are not going to feel comfortable coming forward and getting treatment. And others will hesitate to step up and provide support.

I will always remember the young couple I met in Oklahoma who had lost their son to an opioid overdose. They told me that previously in their life whenever they had a struggle—a job loss or other health issue in the family—neighbors would come over, they would drop off food, they would visit and sit with them in their living room and hold their hands to see if they were okay. When their son died after opioid use disorder, it was silent. Nobody came over. It’s a very common story of how people feel ashamed, they feel uncomfortable, they don’t know quite what to say. So they stay away, which is the worst thing possible during these times of great pain and distress.

I do think we have made progress in the last few years. There are more people stepping forward to tell their stories. There are more people and practitioners who are embracing the importance of talking to their patients about substance use disorders and getting involved in treating them. But the truth is, we still have many people in the country who feel ashamed of what they’re dealing with. We still have many family members who feel that this is a source of shame to have a loved one struggling with a substance use disorder.

To me, this is much bigger than substance use disorders. This is a broader cultural issue of how we think about strength and vulnerability. We have defined strength in modern society as the loudest voice in the room or the person with the most physical prowess, the person who’s aggressive in negotiations, and the person who’s famous.
But I don’t think that’s what strength really is. Strength is so often displayed in moments of vulnerability when people have the courage to open up and be themselves. Strength is defined by the people who have the courage to display love, patience, and compassion, especially when it’s difficult. That’s what real strength is.

One of my hopes is that, as a society, we can ultimately redefine strength. As we think about our children and what we want them to be, we cannot aspire for them to be the loudest voice in the room. We can aspire for them to be the most-thoughtful, the most-welcoming, the most-inviting, the most-compassionate voice in the room.

If we truly want to be a society that’s grounded in love, compassion, and kindness, if we truly recognize those as the sources of strength and healing, we have to value those in our workplaces. They have to be reflected in our promotion systems. We have to value them in the classroom. Ultimately, we’ve got to build our lives around them.

That is a broader lesson that I took from all of the conversations I’ve had with people who struggle with opioid use disorders. What I took was, yes, we need medication and assisted treatment; yes, we need counseling services; yes, we need social services and wraparound services and recovery services. But the engine that will drive our healing is fundamentally the love and compassion that come from human relationships.

We all have the ability to heal because we all have the ability to be kind and to love one another. That’s the lesson that it took me more than two decades to learn in medicine. More important than any prescription that I could write is the compassion that I could extend to patients simply by listening, by showing up, by being present in their lives. We all have that ability, regardless of what degrees follow our name.

Collins: Vivek, this has been a wonderful conversation. We are fortunate to have you as our Surgeon General at this time, when we need lots of love and compassion.

Murthy: Thank you so much, Francis.

Links:

Opioids (National Institute on Drug Abuse/NIH)

Opioid Overdose Crisis (NIDA)

Vice Admiral Vivek H. Murthy (U.S. Department of Health and Human Services, Washington, D.C.)

Helping to End Addiction Long-term (HEAL) Initiative (NIH)

Video: Emotional Well Being and the Power of Connections to Fight the Opioid Epidemic (HEAL/NIH)

Posted In: Generic

Tags: addiction, adolescents, anxiety, Chronic Pain, COVID-19, depression, HEAL, HEAL Initiative, Helping to End Addiction Long-term, Instagram, loneliness, mental health, opioid crisis, opioid use disorder, opioids, overdose, pandemic, personal relationships, prevention, resilience, social media, social stigma, social support, stigma, stress, substance use disorders, support systems, Surgeon General Murthy, teen depression, telemedicine, TikTok, U. S. Surgeon General, Vivek Murthy, well-being, young adults

Lessons Learned About Substance Use Disorders During the COVID-19 Pandemic

Posted on April 8th, 2021 by Dr. Francis Collins

Every spring, I and my colleague Dr. Nora Volkow, Director of NIH’s National Institute on Drug Abuse (NIDA), join with leaders across the country in the Rx Drug Abuse and Heroin Summit. Our role is to discuss NIH’s continued progress in tackling our nation’s opioid crisis. Because of the continued threat of COVID-19 pandemic, we joined in virtually for the second year in a row.

While the demands of the pandemic have been challenging for everyone, biomedical researchers have remained hard at work to address the opioid crisis. Among the many ways that NIH is supporting these efforts is through its Helping to End Addiction Long-Term (HEAL) Initiative, which is directing more than $1.5 billion to researchers and communities across the country.

Here’s a condensed transcript of our April 6th video dialogue, which focused on the impact of the COVID-19 pandemic on people struggling with substance use disorders and those who are trying to help them.

Collins: What have we learned so far through HEAL? Well, one thing HEAL is doing is tackling the need for pain treatments that help people avoid the risks of opioids. This research has uncovered new targets and therapeutics for different types of pain, including neuropathic, post-surgical, osteoarthritic, and chemotherapy induced. We’re testing implanted devices, such as electrodes and non-invasive nerve stimulation; and looking at complementary and integrative approaches, such as phone-based physical therapy for low back pain.

Through HEAL, we’ve launched a first-in-human test of a vaccine to protect against the harmful effects of opioids, including relapse and overdose. We’re also testing a tool that provides pharmacists with a validated opioid use disorder risk measure. The goal is to identify better who’s at high risk for opioid addiction and to determine what kind of early intervention could be put in place.

Despite COVID, many clinical studies are now recruiting participants. This includes family-based prevention programs, culturally tailored interventions for hard-hit American Indian populations, and interventions that address social inequities, such as lack of housing.

We are also making progress on the truly heart-breaking problem of babies born dependent on opioids. HEAL has launched a study to test the effectiveness of a new approach to care that measures the severity of a baby’s withdrawal, based on their ability to eat, sleep, and be consoled. This approach helps provide appropriate treatment for these infants, without the use of medication when possible. We’re also developing novel technologies to help treat neonatal opioid withdrawal syndrome, including a gently vibrating hospital bassinet pad that’s received breakthrough device designation from the FDA.

2020 was an extraordinary year that was tragic in so many ways, including lives lost and economic disasters that have fallen upon families. The resilience and ingenuity of the scientific community has been impressive. Quick pivoting has resulted in some gains through research, maybe you could even call them silver linings in the midst of this terrible storm.

Nora, what’s been at the forefront of your mind as we’ve watched things unfold?

Volkow: When we did this one year ago, we didn’t know what to expect. Obviously, we were concerned that the stressors associated with a pandemic, with unknowns, are factors that have been recognized for many years to increase drug use. Unfortunately, what we’ve seen is an increase in drug use of all types across the country.

We have seen an exacerbation of the opioid epidemic, as evidenced by the number of people who have died. Already, in the 12 months ending in July 2020, there was a 24 percent increase in mortality from overdoses. Within those numbers, there was close to a 50 percent increase in mortality associated with fentanyl. We’re also seeing an increase, not just in deaths from fentanyl and other synthetic opioids, but in deaths from stimulant drugs, like cocaine and methamphetamine. And the largest increases have been very much driven by drug combinations.

So, we have the perfect storm. We have people stressed to their limits by decreases in the economy, the loss of jobs, the death of loved ones. On the other hand, we see dealers taking the opportunity to bring in drugs such as synthetic opioids and synthetic stimulants and distribute them to a much wider extent than previously seen.

Collins: On top of that, people are at risk of getting sick from COVID-19. What have we learned about the risks of coronavirus illness for people who use drugs?

Volkow: It is a double whammy. When you look at the electronic health records about the outcomes of people diagnosed with substance use disorders, you consistently see an increased risk for getting infected with COVID-19. And if you look at those who get infected, you observe a significantly increased risk of dying from COVID.

What’s driving this vulnerability? One factor is the pharmacological effects of these drugs. Basically, all of the drugs of abuse that result in addiction, notably opioids, damage the cardiopulmonary system. Some also damage the immune system. And we know that individuals who have any disruption of cardiovascular health, pulmonary health, immune function, or metabolism are at higher risk of getting infected with COVID-19 and having adverse outcomes.

But there’s another factor that’s as important—one that’s very tractable. It is the way in which our society has dealt with substance use disorders: not actually treating them as a disease that requires intervention and support for recovery. The stigmatization of individuals with addiction, the lack of access to treatment, the social isolation, have all created havoc by making these individuals so much more vulnerable to get infected with COVID-19.

They will not go to a doctor. They don’t want to be stigmatized. They need to go out into the streets to get access to the drugs. Many times, they don’t have a choice of what drugs to take because they cannot afford anything except what’s offered to them. So, many, especially those who are minorities, end up homeless or in jails or prison. Even before COVID, we knew that prisons and jails are places where infections can transmit extraordinary rapidly. You could see this was going to result in very negative outcomes for this group of individuals.

Collins: Nora, tell us more about the trends contributing to the current crisis. Maybe three or four years ago, what was going straight up was opioid use, especially heroin. Then, fentanyl started coming up very fast and that has continued. Now, we are seeing more stimulants and mixing of different types of drugs. What is the basis for this?

Volkow: At the beginning of the opiate pandemic, mortality was mainly associated with white Americans, many in rural or semi-suburban areas of the Appalachian states and in New Mexico and Arizona. That has shifted. The highest increase in mortality from opioids, predominantly driven by fentanyl, is now among Black Americans. They’ve had very, very high rates of mortality during the COVID pandemic. And when you look at mortality from methamphetamine, it’s chilling to realize that the risk of dying from methamphetamine overdose is 12-fold higher among American Indians and Alaskan Natives than other groups. This should make us pause to think about what’s driving these terrible racial disparities.

As for drug combinations, many deaths from methamphetamine or cocaine—an estimated 50 percent—are linked to these stimulant drugs being combined with fentanyl or heroin. Dealers are lacing these non-opioid drugs with cheaper, yet potent, opioids to make a larger profit. Someone who’s addicted to a stimulant drug like cocaine or methamphetamine is not tolerant to opioids, which means they are going to be at high risk of overdose if they get a stimulant drug that’s laced with an opioid like fentanyl. That’s been contributing to the sharp rise in mortality from non-opioid drugs.

Collins: I’m glad you raised the issue of health disparities. 2020 will go down as a year in which our nation had to focus on three public health crises at once. The first is the crisis of opioid use disorder and rising mortality from use of other drugs. The second is COVID-19. And the third is the realization, although the problem has been there all along, that health disparities continue to shorten the lives of far too many people.

The latter crisis has little to do with biology, but everything to do with the way in which our society still is afflicted by structural racism. We at NIH are looking at this circumstance, realizing that our own health disparities research agenda needs to be rethought. We have not fully incorporated all the factors that play out in health inequities and racial inequities in our country.

You were also talking about how stimulants have become more widespread. What about treatments for people with stimulant use disorders?

Volkow: For opioid addiction, we’re lucky because we have very effective medications: methadone, buprenorphine, naltrexone. On top of that, we have naloxone, Narcan, that if administered on time, can save the life of a person who has overdosed.

We don’t have any FDA-approved medication for methamphetamine addiction, and we don’t have any overdose reversal for methamphetamine. At the beginning of this year, we funded a large clinical trial aimed at investigating the benefits of the combination of two medications that were already approved as anti-depressants and for the treatment of smoking cessation and alcoholism. It found this combination significantly inhibits the urge to take drugs and therefore helps people stay away from use of methamphetamine. Now, we want to replicate these findings, and to tie that replication study in with guidelines from the FDA on what is needed to approve our new indication for these medications. Why? Because then insurance can cover it, and that will increase the likelihood that people will get treated.

Another exciting possibility is a monoclonal antibody against methamphetamine that’s in Phase 2 clinical trials. If someone comes into the emergency room with an overdose of a combination of opioid and methamphetamine, naloxone often will not work. But this monoclonal antibody with naloxone may offer a greater likelihood of success.
Another thing that’s promising is that investigators have been able to modify monoclonal antibodies so they stay in the bloodstream for a longer time. That means we may someday be able to use this passive immunization approach as a treatment for methamphetamine addiction.

Collins: That’s good to hear. Speaking of progress, is there any you want to point to within HEAL?

Volkow: There’s a lot of excitement surrounding medication development. We’re interested in developing antidotes that will be more effective in reversing overdose deaths from fentanyl. We’re also interested in providing longer lasting medications for treatment of opioid use disorders, which would improve the likelihood of patients being protected from overdoses.

The Justice Community Opioid Innovation Network (JCOIN) is another HEAL landmark project. It involves a network of researchers that is working with judges and with the workers in jail and prison systems responsible for taking care of individuals with substance use disorders. Through this network, we’ve been able to start to harmonize practices. One thing that’s been transformative in the jail and prison system has been the embracing of telehealth. In the past, telehealth was not much of a reality in jails and prisons because of the fear of it could lead to communications that could perhaps be considered dangerous. That’s changed due to COVID-19. Now, telehealth is providing access to treatment for individuals in jail and prison, many of them with substance use disorders.

Also, because of COVID, many nonviolent individuals in jails and prisons were released. This gives us an opportunity to evaluate how best to help such individuals achieve recovery from substance use disorders. Hopefully we can generate data to show that there are much more effective strategies than incarceration for dealing with substance use disorders.

The HEALing Communities Study, involves Massachusetts, New York, Ohio, and Kentucky—four of the states with the highest rates of mortality from overdoses from the inception of the opioid epidemic. By implementing a battery of interventions for which there is evidence of benefit, this ambitious study set out to decrease overdose mortality by 40 percent in two years. Then, came COVID and turned everything upside down. Still, because we consolidated interactions between agencies, we’ve been able to apply support systems more efficiently in those communities in ways that have been very, very reinforcing. Obviously, there’ve been delays in implementation of interventions that require in-person interactions or that involve hospital emergency departments, which have been saturated with COVID patients.

We’ve learned a lot in the process. I may be too optimistic, but I do believe that we can stay on goal.

Collins: Now, I’d like to transition to a few questions from people who subscribe to the HEAL website. Announced at this meeting three years ago, the HEAL Initiative involves research participants and patients and stakeholders—especially people who have lived experience with pain, addiction, or both.

Let’s get to the first question: “What is NIH doing through HEAL to address the stigma that prevents people who need opioid medications for treatment from getting them?”

Volkow: A crucial question. As we look at the issue of stigma, we need to recognize that there are structural issues in how our society is prioritizing the importance of substance use disorders and the investments devoted to them. And we need to recognize that substance use disorder doesn’t exist in isolation; it is frequently comorbid with mental illness.

We need to listen. Some of the issues that we believe are most problematic are not. We need to empower these communities to speak up and help them do so. This is probably one of the most important things that we can do in terms of addressing stigma for addiction.

Collins: Absolutely. The HEAL Initiative has a number of projects that are focusing on stigma and coming up with tools to help reduce this. And here’s our second question: “In small communities, how can we provide more access to medications for opioid use disorder?”

Volkow: One project funded through HEAL was to evaluate the effectiveness of community pharmacies for delivering buprenorphine to individuals with opioid use disorder. The results show that patients receiving buprenorphine through community pharmacies in rural areas had as good outcomes as patients being treated by specialized clinicians on site.
Another change that’s made things easier is that in March 2020, the DEA relaxed its rules on how a physician can prescribe buprenorphine. In the past, you needed to go physically to see a doctor. Now, the DEA allows a patient to be initiated on buprenorphine through telehealth, and that’s opened the possibility of greater access to treatment in rural communities.

My perspective is let’s look at innovative ways of solving problems. Because the technology is changing in so many ways and so rapidly, let’s take advantage of it.

Collins: Totally with you on that. If there’s a silver lining to COVID-19, it’s that we’ve been forced to take stock of the ways we’ve been doing things. We will learn from this pandemic and change the way we approach so many things in health and medicine as a result. Certainly, opioid use disorder ought to be very high on that list. Let’s move on to another question: “What is the HEAL initiative doing to promote prevention of opioid use?”

Volkow: This is where the HEAL initiative is aiming to provide alternative treatments for the management of pain that reduce the risk of addiction.

Then there’s the issue of prevention in people who start to take opioids because they either want to get high or escape. With the COVID pandemic, we’ve seen increases in anxiety and in depression. Those are factors that can put a teenager or young adult on a trajectory for higher risk of substance use disorders.

So, what is HEAL doing? There is prevention research specifically targeted, for example, at the transition from adolescence to young adulthood. That is the period of greatest vulnerability of uptake of opioids, or drugs of misuse. We’re also targeting minority groups that may be at very, very high risk. We want to be able to understand the factors that make them more vulnerable to tailor prevention interventions more effectively.

Collins: Today, we’ve shared some of the issues that NIH is wrestling with in its efforts to address the crisis of opioid misuse and overdose, as well as other drugs that are now very much part of the challenge. To learn more, go to the HEAL website. You can also send us your thoughts through the HEAL Idea Exchange.

These developments give me hope in the wake of a very difficult year. Clearly, we still have the capacity to work together, we are resilient, and we are determined to put an end to our nation’s opioid crisis.

Volkow: Francis, I want to thank you for your incredible leadership and your support. I hope the COVID pandemic will bring forth a more equitable system, in which all people are given the chance for resilience that maximizes their life, happiness, and productivity. I think science is an extraordinary tool to help us do that.

Links:

Video: The 2021 Rx Drug Abuse & Heroin Summit: Francis Collins with Nora Volkow (NIH)

COVID-19 Research (NIH)

Helping to End Addiction Long-term (HEAL) Initiative (NIH)

HEAL Idea Exchange (NIH)

National Institute on Drug Abuse (NIH)

Rx Drug Abuse & Heroin Summit, A 2021 Virtual Experience

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Tags: addiction, addiction treatment, African American health, American Indian, anxiety, buprenorphine, chemotherapy-induced pain, clinical trial, conversation, COVID-19, depression, drugs, fentanyl, HEAL, HEAL Idea Exchange, health disparities, Helping to End Addiction Long-term, heroin, homeless, jail, JCOIN, Justice Community Opioid Innovation Network, methadone, methamphetamine, monoclonal antibody, naloxone, neuropathic pain, Nora Volkow, opioid crisis, opioid epidemic, opioid painkillers, opioid vaccine, osteoarthritic pain, overdose, pain, pandemic, pharmacists, post-surgical pain, prisons, rural health, RxDrug Abuse and Heroin Summit, social stigma, stress, substance use disorders, synthetic opioids, The HEALing Communities Study

Trying to Make Sense of Long COVID Syndrome

Posted on January 19th, 2021 by Dr. Francis Collins

Credit: NIH

More than 400,000 Americans have now lost their lives to COVID-19. But thousands of others who’ve gotten sick and survived COVID-19 are finding that a full recovery can be surprisingly elusive. Weeks and months after seemingly recovering from even mild cases of COVID-19, many battle a wide range of health problems.

Indeed, new results from the largest global study of this emerging “Long COVID syndrome” highlight just how real and pressing this public health concern really is. The study, reported recently as a pre-print on medRxiv, is based on survey results from more than 3,700 self-described COVID “Long Haulers” in 56 countries [1]. They show nearly half couldn’t work full time six months after unexpectedly developing prolonged symptoms of COVID-19. A small percentage of respondents, thankfully, seemed to have bounced back from brief bouts of Long COVID, though time will tell whether they have fully recovered.

These findings are the second installment from the online Body Politic COVID-19 Support Group and its Patient-Led Research for COVID-19, which consists of citizen scientists with a wide range of expertise in the arts and sciences who are struggling with the prolonged effects of COVID-19 themselves. In an earlier survey, this group provided a first-draft description of Long COVID syndrome, based on the self-reported experiences of 640 respondents.

In the new survey-based study led by Athena Akrami, with Patient-Led Research for COVID-19 and University College London, England, the goal was to characterize the experiences of many more people with Long COVID syndrome. They now define the syndrome as a collection of symptoms lasting for more than 28 days.

This second survey emphasizes the course and severity of more than 200 symptoms over time, including those affecting the heart, lungs, gastrointestinal system, muscles, and joints. It took a particularly in-depth look at neurological and neuropsychiatric symptoms, along with the ability of COVID-19 survivors to return to work and participate in other aspects of everyday life.

The 3,762 individuals who responded to the survey were predominately white females, between the ages of 30 and 60, who lived in the United States. As in the previous survey, the study included adults with symptoms consistent with COVID-19, whether or not the infection had been confirmed by a viral or antibody test. That is a potential weakness of the study, as some of these individuals may have had some other inciting illness. But many of the study’s participants developed symptoms early on in the pandemic, when testing was much more limited than it is now.

More than half never sought hospital care. Only 8 percent said that they’d been admitted to the hospital for COVID-19. And yet, 2,464 respondents reported COVID-19 symptoms lasting six months or longer. Most of the remaining respondents also continued to have symptoms, although they had not yet reached the six-month mark.

Among the most common symptoms were fatigue, worsening of symptoms after physical or mental activity, shortness of breath, trouble sleeping, and “brain fog,” or difficulty thinking clearly. The majority—88 percent—said they coped with some form of cognitive dysfunction or memory loss that to varying degrees affected their everyday lives. That includes the ability to make decisions, have conversations, follow instructions, and drive.

Those who had prolonged symptoms of COVID-19 for more than six months reported contending with about 14 symptoms on average. Most also reported that they’d had a relapse of symptoms, seemingly triggered by exercise, mental activity, or just everyday stress. When surveyed, nearly half of respondents said they’d had to reduce their hours at work due to the severity of their symptoms. Another 22 percent weren’t working at all due to their Long COVID.

The findings show that—even in those people who don’t require hospitalization for severe COVID-19—the condition’s prolonged symptoms are having a major impact on lives and livelihoods, both here and around the world. While the number of people affected isn’t yet known, if even a small proportion of the vast numbers of people infected with COVID-19 develop Long COVID syndrome, it represents a significant public health concern.

Another recent study from China further documents the tendency of COVID-19-related symptoms to linger past the usual recovery time for a respiratory virus [2]. The study, published in Lancet, showed that six months after the onset of illness, more than 75 percent of people hospitalized with COVID-19 in Wuhan between January and May 2020 continued to report at least one symptom. Fatigue, muscle weakness, sleep difficulties, anxiety, and depression all were common. More than half of individuals also had significant persistent lung abnormalities, which were more common in those who’d been more severely ill.

It’s essential for us to learn all we can about how SARS-CoV-2, which is the coronavirus that causes COVID-19, leads to such widespread symptoms. It’s also essential that we develop ways to better treat or prevent these symptoms. The NIH held a workshop last month to summarize what is known and fill in key gaps in our knowledge about Long COVID syndrome, which is clinically known as post-acute sequelae of COVID-19 (PASC). In December, Congress authorized funding for continued research on PASC, including an appropriation of funds for NIH to support continued study of these prolonged health consequences.

As these efforts and others proceed in the coming months, the hope is that we’ll gain much more insight and get some answers soon. And, if you’ve had or are currently experiencing symptoms of COVID-19, there’s still time to share your data by participating in the Patient-Led Research for COVID-19’s second survey.

References:

[1] Characterizing Long COVID in an international cohort: 7 months of symptoms and their impact. David HE et al. Medrxiv. 27 December 27 2020.

[2] 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Huang C, Huang L, et al. Lancet. 2021 Jan 16;397(10270):220-232.

Links:

COVID-19 Research (NIH)

Posted In: News

Tags: anxiety, brain fog, citizen science, cognitive dysfunction, coronavirus, COVID long-haulers, COVID-19, COVID-19 survivor, COVID-19-neurology, COVID-19-symptoms, depression, fatigue, insomnia, long COVID, Long COVID syndrome, long-haulers, lung abnormalities, lungs, novel coronavirus, pandemic, PASC, Patient-led Research for COVID-19, post-acute sequelae of COVID-19, SARS-CoV-2, survey

Building Resilience During the COVID-19 Pandemic

Posted on October 15th, 2020 by Dr. Francis Collins

Dating back to our earliest times, humankind has experienced the psychological impact of a wide range of catastrophes, including famines, floods, earthquakes, wildfires, windstorms, wars, and, last but certainly not least, outbreaks of potentially deadly infectious diseases. We are certainly no exception today as people try to figure out how to cope—and help others cope—with the grief, stress, and anxiety caused by biggest health challenge of our time: the coronavirus 2019 (COVID-19) pandemic.

With more than 215,000 Americans having lost their lives and more than 7.8 million infected since COVID-19 first gripped our nation, the pandemic has taken a profound psychological and emotional toll on us all. Still, behavioral and social science researchers have identified some strategies to help us deal with our fears, and even rise to the challenge of supporting others during this unprecedented time.

Recently, I had an opportunity to discuss the science behind mental health responses to disasters with Dr. George Everly Jr., a psychologist and professor at the Johns Hopkins University Bloomberg School of Public Health, Baltimore. A world-renowned expert with more than 40 years experience studying the psychological impacts of disasters, he co-founded the International Critical Incident Stress Foundation, an organization affiliated with the United Nations. Our conversation took place via videoconferencing from our home offices in Maryland. Here’s a condensed transcript of our chat:

Collins: Good morning! At NIH, we are doing everything we can to keep our scientific mission going by supporting groundbreaking research into COVID-19 and a lot of other things. We’re also deeply committed to helping people manage stress and attend to mental health. So, we’ve invited Dr. Everly to share insights that I believe will help us learn some skills to build resilience. Goodness knows, this is a time where we all need resilience, as well as to help others around us. We’re all called upon, I think, to look after our friends and neighbors in the aftermath of a circumstance like the current pandemic.

Everly: It’s a privilege to spend some time with you today and chat about such an important topic. The topic we typically think about in terms of disasters is the physical response. Today, we’ll talk about the psychological impact of the COVID-19 pandemic. This is actually my third pandemic, having consulted in Hong Kong with SARS and Singapore with H1N1. I’ve also done consulting with Ebola.

However, I will tell you that this pandemic, COVID-19, has been the most challenging. I think we can we agree that mental health is an intrinsic value as it relates to us as humans. Anything that threatens mental health, especially in large numbers, threatens the core fabric of society.

According to the United Nations, we may now be looking at an impending international mental health crisis. Some have called this the “hidden” pandemic: people who previously coped well may have challenges and people who had challenges coping before COVID-19 may have increased challenges. Looking at first responders and frontline workers, we have seen heroic efforts on their part, but not without consequences—and mental exhaustion may be one of them

Collins: How is this crisis similar—and how is it different—from most of the disasters that people have dealt with?

Everly: The first thing is expectations. If we expected COVID-19 to be short lived, we have been remarkably, if not catastrophically, disappointed.

So, this connection occurred to me. A number of years ago, I was interested in the psychological impact of the London Blitz, and I went to England to interview people who went through that night upon night upon night of intractable bombing during World War II. I wanted to find out what helped people make it through. It was very clear that their initial belief that the bombing would be short-lived was tragically violated. They then as a community understood that they had to shift into a different mindset, and realize the Blitz wasn’t a sprint—it was marathon. They’d originally sent their children out into the countryside, but later decided to bring them back in the midst of bombing. I will suggest that psychologically, that was the turn of the war. In fact, research later by Anna Freud found that sending the kids away was psychologically more injurious than keeping them in the city. And I think that’s really important. Realizing that we are in for a long haul with COVID-19, in and of itself may be a game changer.

Collins: A very interesting comparison. I hadn’t thought about it that way—an acute disease becoming chronic.

Tell us a little bit more about the undercurrent of malaise in our country even before this COVID-19 pandemic hit—what economists Angus Deaton and Anne Case have recently written about as the “deaths of despair” and the opioid crisis. We are facing a pandemic from coronavirus, but it didn’t land on a completely blank page. It landed in a circumstance where many people were already feeling significant stress, and where depression was increasing risks of overdoses and suicide.

Everly: Fantastic question. You probably remember the work of Hans Selye, an endocrinologist who actually coined the term “stress.” He said, at any given point in time, we have a limited supply of what he called “adaptive energy.” In the best of conditions, this reservoir is quite high and will allow us to meet unusual challenges. However, I would suggest that the background noise of chronic issues that predated COVID-19 did begin to deplete that reservoir of adaptive energy, making us more vulnerable to things that turned out to be far more challenging than we thought. We were starting with one foot in the hole, so to speak.

Collins: All the more reason why our resilience is being called upon. Piled on top of it, many people are facing the serious challenge of trying to telework from home and trying to manage their responsibilities in terms of children or other family members who need care. My heart goes out to those folks as they struggle with this shared set of responsibilities, probably feeling as if there aren’t enough hours in the day and distractions are always getting in the way.

People are also feeling stressed now about the health of their children. What do we know—and what should we be thinking about—in terms of the mental health impact of the COVID-19 pandemic on kids?

Everly: In the spirit of full disclosure, I’m not a child psychologist. But I have studied trauma, crisis, and disaster for quite a while, and, invariably, children are part of that. One of the most powerful things I have seen in my career is that children often become reflections of their parents. Children not only desire, but they need, stability. My message to parents is that your children rely on you. You must be that strength for them. Even when you think you can’t be strong for yourself, reach down deep inside and say, “This isn’t just about you; it’s about others as well.”

I’ve got three young grandchildren, and this is the message I am telling their parents: “This is an important time. This may be one of the defining milestones in your children’s development. It’s an opportunity to show them how to cope.”

Collins: I have grandkids as well and have been watching how they have adapted. In some instances, I can see how they have actually gained in strength, as they’ve learned that this is an opportunity to face up to a challenge and learn how to cope. It does seem to be a mix of providing that foundation of support, but trying not to prevent children completely from having the experience of realizing they can get through some things themselves.

Everly: We can certainly be overprotective. From studying Olympic athletes, we learned that when they were asked what helped them reach the elite tier and win Olympic medals, they answered: challenge, plus adequate support. While well-intended, I think support alone is misdirected.

Collins: That makes sense. I know, during the current crisis, there is an interest in figuring out, in scientifically rigorous ways, what mental health interventions seem to produce good outcomes. Tell me a little bit more about where we stand as far as the opportunities to be doing these sorts of trials of various interventions. It would be a shame to go through this and then say to ourselves, “We missed a great opportunity there to learn more.”

Everly: It’s tough to do a randomized, controlled trial in the middle of a disaster. There are quite literally ethical issues at play. So, we approximate as best we can. For example, in the past, we built our own model of Psychological First Aid and tested it in two randomized controlled trials and three content validation studies, as well as in structural equation modeling studies. Have we tested it in this current environment? Not yet. There may be others doing that—I’m not sure.

If you take a look at the Cochrane Review on resiliency programs, you will perhaps be a little surprised. The review says there’s not a compelling body of evidence that resiliency programs work. However, we believe they work. We know there is this thing called human resilience and we encourage everyone to keep on trying to study it in scientifically rigorous ways.

Collins: I’m glad that you are. We should not miss the opportunity here to learn, because this is probably not our last pandemic—or our last crisis. Any final words?

Everly: So, with the caveat that I’m a diehard optimist …

Collins: That’s okay. I am too!

Everly: … I truly believe that from the greatest adversities, opportunities can emerge. When I spent three years in New York working after the 9/11 terrorist attack, I thought this is the defining moment, not just of my generation, but of others. I got to see it up close and personal, and worked intimately with various agencies. And I did see opportunities. As a result of 9/11, we changed not just the way we go through airports, but the way we look at trauma from a public health standpoint. Perhaps for the first time, we realized that we need to take a far more active preventative and interventional role.

Now, history repeats itself. I believe that this pandemic will change us for the rest of my life—and I don’t think all those changes need be negative. I think there are huge opportunities. I certainly am eager to investigate this at the highest levels of science. Let’s see why things work when they work and why things don’t work. Then, let’s use that information to build programs and test them in randomized, controlled trials.

I think we will come out of this pandemic better than we went into it. I would encourage people to understand that we’re in this together. Way back in the mid-1800s, Darwin told us that the greatest predictor of resilience was collaboration and cohesiveness. This is a time to reach out to each other.

Collins: I totally agree with that. You’re making a really good point: social distancing doesn’t have to mean anything more than physical distancing. We can stay socially close and reach out to each other in different ways.
We’re going to get through this, but get through it in a way that will change us. We will be changed by becoming stronger and more resilient, having learned some lessons about ourselves and about each other. We cannot simply hide our heads under our pillows and wait for this to pass. When you wake up in the morning, say to yourself: “I’m engaged in something that matters. I’m not just a passive victim of this terrible pandemic. I’m trying to do what I can and work toward getting us through.”

Many thanks, Professor Everly, for all your good work and for giving us this time to reflect on this important area of research and how to make the most of it.

Links:

Coronavirus (COVID-19) (NIH)

George S. Everly (Johns Hopkins University Bloomberg School of Public Health/Baltimore)

Video: Coping with the Mental Health Effects of COVID-19, George Everly with Francis Collins (NIH VideoCast)

The Power of Psychological First Aid. Dome. Minkove JF. March/April 2018. (Johns Hopkins Medicine/Baltimore)

Coping with Stress (Centers for Disease Control and Prevention)

Coping With Stress During Infectious Disease Outbreaks (Substance Abuse and Mental Health Services Administration)

Talking with Children: Tips for Caregivers, Parents, and Teachers during Infectious Disease Outbreaks. (SAMHSA)

National Suicide Prevention Lifeline

SAMHSA’s Disaster Distress Helpline, 1-800-985-5990

National Suicide Prevention Hotline, 1-800-273-TALK (8255); TTY number 1-800-799-4TTY (4889)

Posted In: Generic

Tags: adaptive energy, Angus Deaton, Anna Freud, Anne Case, anxiety, behavioral science, child health, coping, COVID-19, crisis, disasters, Ebola, George Everly, H1N1, Hans Selye, International Critical Incident Stress Foundation, London Blitz, mental health, novel coronavirus, pandemic, Psychological First Aid, resilience, resiliency programs, social science, stress, suicide, suicide prevention, trauma, United Nations

Dealing with Stress, Anxiety, and Grief during COVID-19

Posted on April 7th, 2020 by Dr. Francis Collins

If somebody had told you last year that that our country, along with the whole world, would soon be facing a major health challenge like the coronavirus disease 2019 (COVID-19) pandemic, you’d have thought it almost unimaginable. Yet here we are.

To help flatten the pandemic’s deadly curve, a great many of us have been asked to remain at home. I have been faithfully adhering to that recommendation—I haven’t been to my office or lab at NIH in almost three weeks, though I can’t remember a time where I have worked harder. While helping to protect ourselves and others, this physical distancing can affect our mental well-being.

Recently, I had an opportunity to discuss these aspects of COVID-19 with Dr. Joshua Gordon, Director of NIH’s National Institute of Mental Health. Our conversation took place via videoconferencing, with him linking in from his home in the New York area and me from my home in Maryland. Here’s a condensed transcript of our chat:

Collins: So, Josh, tell me how you’re doing there. How’s everybody coping?

Gordon: Right now, my family and I are doing fine. My daughter and I are ensconced here at home, both working from home. She’s finishing up high school online and my wife works for New York City. She’s an essential employee, so she’s still going into work but, fortunately, she’s able to make sure that her workspace is very sparse and she’s able to commute by herself.

Collins: I’m glad you’re okay. Exactly how do you name this kind of stress that everybody’s feeling right now? Is it fear? Is it anxiety about being put in such an area of uncertainty? Is it just grief, the sense that something really profound has happened here and we are losing things in terms of our ability to move around freely? Certainly, we also grieve deeply about the suffering and the death that we see.

Gordon: For different people, it’s different combinations. I know that I feel anxiety for myself and my family in terms of our health. But it’s not just anxiety about contracting the coronavirus, it’s also fear and anxiety about what’s happening to society, what’s happening to our economy, what’s happening to our friends and relatives.

And then there is tremendous grief. We’ve acknowledged that we’ve all lost something already. Right? We’ve lost our normal day-to-day interactions. We’ve lost our ability to physically connect with people and it makes it more challenging to socially connect with people. And we’ve lost that sense of certainty and self-power.

Collins: Talking to my wife Diane about this, I think the grief part of it was something we were both feeling, but hadn’t quite named. Somehow being able to talk about it, experience it, and not try to run away from it turned out to be helpful.

Gordon: Yes, it’s important to talk about it. For most people, it’s a matter of being able to talk about your feelings, get it out into the open, and hear from others that are going through the same thing. They’re your friends that you’re Zooming with, they’re your parents or grandparents that you’re talking to on the phone.

Collins: I hope everybody will feel a little more free to be honest about what they are going through. Maybe sometimes we try to just be tough and keep it all to ourselves and don’t want others around us to be influenced, if we’re talking about our own emotions. But we need to share those things. Besides that, what other things, can be helpful to people who are trying to cope with the current circumstances?

Gordon: One important thing is to focus on the facts. There’s a lot of rumor, there’s a lot of hyperbole out there, and there’s a lot of, frankly, uncertainty. But to the extent that you can, learn and share the facts about the virus. If you know what’s happening, it reduces the uncertainty.

At the same time, one can get so taken up with reading the daily news, listening to the various news conferences that are going on, checking the websites, etc., that it becomes all-consuming. So, it’s really important to set aside periods of each day where you turn off social media, you turn off the TV, turn off the news, and do something that you enjoy. It could be art, it could be exercise, it could be picking up the phone and talking to someone about something other than COVID.

The other thing that’s really important is to take care of your body in addition to your mind. Taking care of your body can help your mind do better. So, yoga, exercise, resting, naps, regular meals, all these things can be helpful. Alcohol is often used as an escape mechanism when you’re feeling stressed. That can be a little tricky or dangerous, so try to avoid drinking excessively.

Connecting with others is really important in this day of physical distancing. I like to call it physical distancing, rather than social distancing, because I think we can be socially intimate and physically distant. So, connect with others, reach out to people, use digital tools, use telephones, use email and text, write a letter.

Collins: A letter?

Gordon: Yes, why not? I haven’t gotten mail for three days. Just saying. So, write a letter, connect with people that you can unwind with, that you can get joy from.

Collins: My wife Diane just stepped in and I want to have her to come over for a minute and say something about this, because I think part of the grief we were feeling was this disconnection from face-to-face interactions with people. Diane’s a very sociable person and this is particularly hard when you’re so isolated in one place. But she came up with something yesterday that seemed to be a help.

Diane Baker: Yes. I’ve got to say, the shelter in place order here in Maryland just surprised me. It took me down a couple of notches and I can’t say it was warranted, I was like I can’t take this. Even though it’s what we’ve been doing, it just emotionally really got to me. And so a friend came up with this idea. She went for a walk in her neighborhood, I went for a walk in my neighborhood, we pulled our phones out and we had a conversation. Even though it was cold rainy day, we didn’t mind it because we were talking to each other. So, we’re going to try and do that on a regular basis.

Gordon: You’re right, your social connectedness really helps. Like I can reach out to my parents in North Carolina, I can reach out to my brother in Philadelphia. We’ve had almost nightly Zoom get-togethers and I actually feel like I’m seeing my relatives more these last couple of weeks than I have in months.

Collins: That’s interesting. We’ve done that too. Every Sunday now we have a Zoom meeting with my daughters and my grandkids.

Diane Baker: The other thing I think it’s done is forced us to be more intentional about our communication. I think that’s something we take for granted. For instance, I have this book club I’ve been a part of for a long time, but we always talk books and politics and topical issues. Now, I’m starting to reach out to them on email and say, “Hey, I’m having a real tough time,” and we’re supporting each other in a way that we haven’t before. It’s been very nice. I’ll let you guys go on..

Gordon: Nice to see you, Diane.

Collins: I think we all feel this urge to do something, to try to contribute in some way. In many ways, we feel a little paralyzed by the fact that we’re stuck indoors and all of the things you might like to do might be risky for yourself or other people. What can we do as far as actions to help other people?

Gordon: Those of you who are working directly on COVID can take a lot of pride in the fact that you’re contributing to that mission. But everyone is contributing to that mission by staying home. I would add a more practical bent to all this, which is that it is important to set goals and priorities for yourself. Finally, there are volunteer opportunities that can be done remotely. There are donations that are being accepted. So, I encourage you, if you feel so moved and have the means to do so, contribute in that way.

Collins: Parents are worried about their kids in terms of how this is affecting them. So, what kind of advice can you give to parents about how to interact with children in this very unusual situation?

Gordon: Kids are, I’m sure, feeling anxious. First, recognize what they’re going through. Talk to them about it, find out what’s concerning them.

Kids always surprise you. They’re not necessarily anxious or worried about the things that you’re anxious or worried about. They might be worried about getting COVID, but they might also just be worried that they’re going to miss their best friend’s birthday next week. So, if you find out what’s bothering them, then you can help them. You can have them Zoom a happy birthday song or connect in some other way.

Reassuring them can help. But, more importantly, it’s just answering their questions as honestly as you can. When you don’t know, admit that you don’t, but say that you’ll be there for them.

Collins: Everybody is facing a certain amount of stress, anxiety, and grief at this time, but it hits some people even harder. What would be the signs that this is getting into a circumstance that might require some additional help?

Gordon: Let’s talk about how we recognize when this might be a thing that we can’t deal with and that is sending us over the edge. I went out grocery shopping last Friday. I managed to find a mask to wear and gloves, but I actually couldn’t take it. I was so anxious. I bought a few things and I had to leave. I felt in me something I’ve really never felt before. My heart started racing, I started breathing fast. I was getting a panic attack. That was something pushing me over the edge in ways that I hadn’t been challenged before.

If that happens to you, recognize it and seek help. So, what are the signs? We’re all feeling anxious, but if you feel so anxious you can’t get your work done, you actually can’t do the thing that you set out to do, reach out for help either from a friend or from a professional. Other signs would be you’re starting to withdraw from people, having trouble sleeping, change in appetite, change in physical energy levels, or starting to become irritable or angry.

For those with pre-existing mental illnesses, it’s really important that they reach out to their providers and find ways of connecting. Every mental health provider that I know of right now is moving to telehealth sessions. Not everyone is used to teleconferences, not everyone knows how to use them. So, plan in advance with your provider how you’re going to contact with them so that you can get the help you need when you need it. Make sure that you have enough medication in-house and work out with your pharmacy how you can get it delivered rather than having to go pick it up, whether that’s from a mail order pharmacy or getting your local pharmacy to deliver to you.

Finally, there are hot lines. For those experiencing distress with the COVID epidemic, the Substance Abuse and Mental Health Service Administration has the Disaster Distress Helpline. That’s 800-985-5990 or text “TalkWithUs” to 66746. For those who are really struggling, and are thinking of hurting or killing themselves, there’s the National Suicide Prevention Lifeline at 800-273-8255 or you can text “HOME” to the Crisis Text Line at 741741.

Collins: Before we close, I’d like to talk about how, despite the stress, the anxiety, and the grief that we’re all feeling, we might somehow learn something pretty significant about ourselves during this pandemic. Can you say something about that?

Gordon: One thing we know is that resilience isn’t necessarily about something you already have. It’s something that you learn, that people who’ve been through challenging times and risen to the occasion, they learn from that. They become resilient. They learn how to get through challenging situations in the future.

For many of us, this is an opportunity to learn more about ourselves and how we can grow as people, as human beings, and as fathers and mothers and daughters and sons. This is an opportunity to prove that we can respond to an emergency like this in a way that is thoughtful, in a way that is caring, and in a way that contributes to improving the situation for all of us

Collins: It does call us, doesn’t it, to focus on things that in our daily rush of business as usual, we neglect to think about. What are we really here for? What’s the meaning of all of this? What is our responsibility to try to make the world a better place?

I’d predict that all of us who are living through this COVID-19 experience will look back on it as a time of special significance in terms of what we learned about ourselves and about the perspective of what really matters in this world. So, yes, it’s stressful, it’s full of grief and sorrow, but maybe it’s a way in which you can gain something to carry forward. Josh, thank you so much.

Resources:

The Disaster Distress Helpline, 1-800-985-5990 (Substance Abuse and Mental Health Services Administration)

National Suicide Prevention Lifeline, 1-800-273-8255

Crisis Text Line, 741741

Coping with Coronavirus: Managing Stress, Fear, and Anxiety, Director’s Messages (National Institute of Mental Health/NIH)

Stress and Coping, Coronavirus (Centers for Disease Control and Prevention)

Coronavirus (COVID-19) (NIH)

Posted In: Generic

Tags: alcohol, anxiety, behavior, children, communcation, coping, coronavirus, COVID-19, family, grief, human interaction, Josh Gordon, Joshua Gordon, mental health, National Institute of Mental Health, pandemic, panic attack, stress, suicide prevention, videoconferencing, wellness

Discovering a Source of Laughter in the Brain

Posted on February 12th, 2019 by Dr. Francis Collins

Illustration showing how an electrode was inserted into the cingulum bundle. Courtesy of American Society for Clinical Investigation

If laughter really is the best medicine, wouldn’t it be great if we could learn more about what goes on in the brain when we laugh? Neuroscientists recently made some major progress on this front by pinpointing a part of the brain that, when stimulated, never fails to induce smiles and laughter.

In their study conducted in three patients undergoing electrical stimulation brain mapping as part of epilepsy treatment, the NIH-funded team found that stimulation of a specific tract of neural fibers, called the cingulum bundle, triggered laughter, smiles, and a sense of calm. Not only do the findings shed new light on the biology of laughter, researchers hope they may also lead to new strategies for treating a range of conditions, including anxiety, depression, and chronic pain.

In people with epilepsy whose seizures are poorly controlled with medication, surgery to remove seizure-inducing brain tissue sometimes helps. People awaiting such surgeries must first undergo a procedure known as intracranial electroencephalography (iEEG). This involves temporarily placing 10 to 20 arrays of tiny electrodes in the brain for up to several weeks, in order to pinpoint the source of a patient’s seizures in the brain. With the patient’s permission, those electrodes can also enable physician-researchers to stimulate various regions of the patient’s brain to map their functions and make potentially new and unexpected discoveries.

In the new study, published in The Journal of Clinical Investigation, Jon T. Willie, Kelly Bijanki, and their colleagues at Emory University School of Medicine, Atlanta, looked at a 23-year-old undergoing iEEG for 8 weeks in preparation for surgery to treat her uncontrolled epilepsy [1]. One of the electrodes implanted in her brain was located within the cingulum bundle and, when that area was stimulated for research purposes, the woman experienced an uncontrollable urge to laugh. Not only was the woman given to smiles and giggles, she also reported feeling relaxed and calm.

As a further and more objective test of her mood, the researchers asked the woman to interpret the expression of faces on a computer screen as happy, sad, or neutral. Electrical stimulation to the cingulum bundle led her to see those faces as happier, a sign of a generally more positive mood. A full evaluation of her mental state also showed she was fully aware and alert.

To confirm the findings, the researchers looked to two other patients, a 40-year-old man and a 28-year-old woman, both undergoing iEEG in the course of epilepsy treatment. In those two volunteers, stimulation of the cingulum bundle also triggered laughter and reduced anxiety with otherwise normal cognition.

Willie notes that the cingulum bundle links many brain areas together. He likens it to a super highway with lots of on and off ramps. He suspects the spot they’ve uncovered lies at a key intersection, providing access to various brain networks regulating mood, emotion, and social interaction.

Previous research has shown that stimulation of other parts of the brain can also prompt patients to laugh. However, what makes stimulation of the cingulum bundle a particularly promising approach is that it not only triggers laughter, but also reduces anxiety.

The new findings suggest that stimulation of the cingulum bundle may be useful for calming patients’ anxieties during neurosurgeries in which they must remain awake. In fact, Willie’s team did so during their 23-year-old woman’s subsequent epilepsy surgery. Each time she became distressed, the stimulation provided immediate relief. Also, if traditional deep brain stimulation or less invasive means of brain stimulation can be developed and found to be safe for long-term use, they may offer new ways to treat depression, anxiety disorders, and/or chronic pain.

Meanwhile, Willie’s team is hard at work using similar approaches to map brain areas involved in other aspects of mood, including fear, sadness, and anxiety. Together with the multidisciplinary work being mounted by the NIH-led BRAIN Initiative, these kinds of studies promise to reveal functionalities of the human brain that have previously been out of reach, with profound consequences for neuroscience and human medicine.

Reference:

[1] Cingulum stimulation enhances positive affect and anxiolysis to facilitate awake craniotomy. Bijanki KR, Manns JR, Inman CS, Choi KS, Harati S, Pedersen NP, Drane DL, Waters AC, Fasano RE, Mayberg HS, Willie JT. J Clin Invest. 2018 Dec 27.

Links:

Video: Patient’s Response (Bijanki et al. The Journal of Clinical Investigation)

Epilepsy Information Page (National Institute of Neurological Disease and Stroke/NIH)

Jon T. Willie (Emory University, Atlanta, GA)

NIH Support: National Institute of Neurological Disease and Stroke; National Center for Advancing Translational Sciences

Posted In: News

Tags: anxiety, awake neurosurgery, brain, BRAIN Initiative, brain mapping surgery, brain surgery, calm, Chronic Pain, cingulum bundle, depression, epilepsy, iEEG, intracranial electroencephalography, laughter, neurosurgery, pain, seizures, smiles

Connecting Senescent Cells to Obesity and Anxiety

Posted on January 8th, 2019 by Dr. Francis Collins

Adapted from Ogrodnik et al., 2019, Cell Metabolism.

Obesity—which affects about 4 in 10 U.S. adults—increases the risk for lots of human health problems: diabetes, heart disease, certain cancers, and even anxiety and depression [1]. It’s also been associated with increased accumulation of senescent cells, which are older cells that resist death even as they lose the ability to grow and divide.

Now, NIH-funded researchers have found that when lean mice are fed a high-fat diet that makes them obese, they also have more senescent cells in their brain and show more anxious behaviors [2]. The researchers could reduce this obesity-driven anxiety using so-called senolytic drugs that cleared away the senescent cells. These findings are among the first to provide proof-of-concept that senolytics may offer a new avenue for treating an array of neuropsychiatric disorders, in addition to many other chronic conditions.

As we age, senescent cells accumulate in many parts of the body [3]. But cells can also enter a senescent state at any point in life in response to major stresses, such as DNA damage or chronic infection. Studies suggest that having lots of senescent cells around, especially later in life, is associated with a wide variety of chronic conditions, including osteoporosis, osteoarthritis, vascular disease, and general frailty.

Senescent cells display a “zombie”-like behavior known as a senescence-associated secretory phenotype (SASP). In this death-defying, zombie-like state, the cells ramp up their release of proteins, bioactive lipids, DNA, and other factors that, like a zombie virus, induce nearby healthy cells to join in the dysfunction.

In fact, the team behind this latest study, led by James Kirkland, Mayo Clinic, Rochester, MN, recently showed that transplanting small numbers of senescent cells into young mice is enough to cause them weakness, frailty, and persistent health problems. Those ill effects were alleviated with a senolytic cocktail, including dasatinib (a leukemia drug) and quercetin (a plant compound). This drug cocktail overrode the zombie-like SASP phenotype and forced the senescent cells to undergo programmed cell death and finally die.

Previous research indicates that senescent cells also accumulate in obesity, and not just in adipose tissues. Moreover, recent studies have linked senescent cells in the brain to neurodegenerative conditions, including Alzheimer’s disease, and showed in mice that dasatinib and quercetin helps to alleviate neurodegenerative disease [4,5]. In the latest paper, published in the journal Cell Metabolism, Kirkland and colleagues asked whether senescent cells in the brain also could explain anxiety-like behavior in obesity.

The answer appears to be “yes.” The researchers showed that lean mice, if allowed to feast on a high-fat diet, grew obese and became more anxious about exploring open spaces and elevated mazes.

The researchers also found that the obese mice had an increase in senescent cells in the white matter near the lateral ventricle, a part of the brain that offers a pathway for cerebrospinal fluid. Those senescent cells also contained an excessive amount of fat. Could senolytic drugs clear those cells and make the obesity-related anxiety go away?

To find out, the researchers treated lean and obese mice with a senolytic drug for 10 weeks. The treatment didn’t lead to any changes in body weight. But, as senescent cells were cleared from their brains, the obese mice showed a significant reduction in their anxiety-related behavior. They lost their anxiety without losing the weight!

More preclinical study is needed to understand more precisely how the treatment works. But, it’s worth noting that clinical trials testing a variety of senolytic drugs are already underway for many conditions associated with senescent cells, including chronic kidney disease [6,7], frailty [8], and premature aging associated with bone marrow transplant [9].

As a matter of fact, just after the Cell Metabolism paper came out, Kirkland’s team published encouraging though preliminary, first-in-human results of the previously mentioned senolytic drug dasatinib in 14 people with age-related idiopathic pulmonary fibrosis, a condition in which lung tissue becomes damaged and scarred [10]. Caution is warranted as we learn more about the associated risks and benefits, but it’s safe to say we’ll be hearing a lot more about senolytics in the years ahead.

References:

[1] Adult obesity facts (Centers for Disease Control and Prevention)

[2] Obesity-induced cellular senescence drives anxiety and impairs neurogenesis. Ogrodnik M et al. Cell Metabolism. 2019 Jan 3.

[3] Aging, Cell Senescence, and Chronic Disease: Emerging Therapeutic Strategies. Tchkonia T, Kirkland JL. JAMA. 2018 Oct 2;320(13):1319-1320.

[4] Tau protein aggregation is associated with cellular senescence in the brain. Musi N, Valentine JM, Sickora KR, Baeuerle E, Thompson CS, Shen Q, Orr ME. Aging Cell. 2018 Dec;17(6):e12840.

[5] Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Bussian TJ, Aziz A, Meyer CF, Swenson BL, van Deursen JM, Baker DJ. Nature. 2018 Oct;562(7728):578-582.

[6] Inflammation and Stem Cells in Diabetic and Chronic Kidney Disease. ClinicalTrials.gov, Sep 2018.

[7] Senescence in Chronic Kidney Disease. Clinicaltrials.gov, Sep 2018.

[8] Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults (AFFIRM-LITE). Clinicaltrials.gov, Dec 2018.

[9] Hematopoietic Stem Cell Transplant Survivors Study (HTSS Study). Clinicaltrials.gov, Sep 2018.

[10] Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. Justice JN, Nambiar AN, Tchkonia T, LeBrasseur K, Pascual R, Hashmi SK, Prata L, Masternak MM, Kritchevsky SB, Musi N, Kirkland JL. EBioMed. 5 Jan. 2019. [Epub ahead of print]

Links:

Healthy Aging (National Institute on Aging/NIH)

Video: Vail Scientific Summit James Kirkland Interview (Youtube)

James Kirkland (Mayo Clinic, Rochester, MN)

NIH Support: National Institute on Aging; National Institute of Neurological Disorders and Stroke

Posted In: News

Tags: Alzheimer’s disease, anxiety, brain, dasatinib, diet, lateral ventricle, mouse study, neuropsychiatric disorders, obesity, quercetin, SASP, senescence-associated secretory phenotype, senescent cells, senolytic drugs, senolytics, zombie cells

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