Using Data to Stem the Tide of Gun Violence in the U.S.

Gun violence and firearm-related deaths are surging in the U.S. since 2020. This paradoxically may lead some people to think that owning a gun is a good idea and indeed gun sales in the U.S. have also been surging since the coronavirus pandemic began. Most gun owners in the U.S. say they own their guns for protection and that they make them feel safer.

         The data on gun ownership actually show quite the opposite. Numerous studies have demonstrated that the presence of a gun in the home increases the risk that a household member will die by firearm-related suicide or homicide. A new study published in April in the Annals of Internal Medicine found that homicides were twice as high among people who lived in households with a gun owner as those who lived in households without guns. The concluding statement from the paper is important:

Homicides and suicides account for 97% of the nearly 40 000 firearm-related deaths in the United States each year. It is implausible that gun access decreases suicide risk, and every rigorous study that has examined this relationship has found a positive association. Nonetheless, if firearm ownership enhanced personal safety in other ways, as many gun owners reportedly believe, tolerating some elevated risk for suicide might be considered a worthwhile tradeoff. This study adds to mounting evidence that no such tradeoff exists, because a gun in the home is associated with higher—not lower—risk for fatal assault. People who do not own handguns but live with others who do bear some of that risk, and the amount they bear appears to be substantial.

More Policing Not Correlated with Violent Crime Reduction

         Believing that owning a gun offers protection is a form of science denial, because the evidence we currently have is clear that it does not. Apparently, owning a firearm does exactly the opposite of what most gun owners believe: it increases the risk that the gun will be used to harm owners themselves or their families. Another belief that many people have is that more policing is a potential solution to stemming the rising tide of gun violence. A recent Brookings Institute report helps us consider if there is evidence to support that claim.

         The report indicates that there is little correlation between increasing police funding and decreasing crime. Even if there were, the report notes that municipalities would still have “to weigh the negative effects that accompany adding more police officers, such as increasing arrests for low-level crimes which contribute to mass incarceration and disproportionately affect Black communities. Exposure to the criminal justice system itself can perpetuate underlying issues that contribute to violent crime and recidivism, such as low socioeconomic status and unemployment, homelessness, and poor mental health.”

         According to the Brookings report, “One of the most evident social factors correlated with violent crime is mental health.” High levels of poor mental health at the community level in aggregate, reflected by measures like overall community levels of depression and anxiety, are correlated with increased rates of violence. Efforts to improve community-level mental health may reduce violent crime. The report notes that “An estimated 20% of police calls are for mental health and substance use crises.” 

         This of course does not mean that most individuals with mental illness are prone to commit violent acts; we know that even though overall people with mental illness are somewhat more likely to to commit violent acts than people without mental illness, the great majority of people with mental illness are not violent. Rather, it suggests that poor overall community mental health and lack of access to mental health care increases the risk for violent crime, including gun-related violence. Furthermore, it begs the question of whether most police officers are properly trained and prepared to deal with the staggering number of calls that involve mental health disturbances.

Police Are Not Prepared for Mental Health Emergencies

         These data suggest that owning a gun is clearly not a solution to dealing with increasing gun-related violence in the U.S. Nor is simply spending more money on policing likely to address the problem. In addition to stricter gun control legislation and addressing the social factors that increase the risk for gun violence, the data indicate that improving access to mental health care facilities may have an impact. Also, we need to develop and evaluate alternatives to standard police responses to mental health emergencies. We have heard people scoff at the idea of “having a social worker respond to a police call,” but in fact there is little evidence to suggest that having police officers respond to calls that involve a person in the midst of a mental health crisis is an effective intervention. Whether police officers can be better trained to respond to mental health emergencies or in fact we should be deploying behavioral health professionals for these calls is an empirical question that critically needs exploring.        

Scientific data alone cannot be the basis for all public policy decisions; these require careful consideration of social needs, politics, and economic realities. But we believe that public policymakers should always ask if there are data relevant to their decisions or if more studies could be useful. Available data tell us that liberalizing gun ownership laws and spending more money on policing are unlikely to lead to meaningful and acceptable reductions in gun violence in the U.S. Rather, we need to consider factors that are known to increase the likelihood for gun violence and design interventions to address them. One of those factors seems clearly to be poor community mental health. Thus, any attempt to reduce gun violence in the U.S. should consider the evidence and include an approach that addresses our police and overall community responses to mental health needs.

Great Science, Terrible Science Communication

The Paxlovid Story

It usually takes, on average, 11 years to develop a new drug. That is one reason why the introduction of an antiviral drug for Covid-19 treatment with the brand name Paxlovid is so remarkable: it was developed in just 20 months. The science that permitted this, as detailed in a STAT news article by Mathew Herper, was impressive indeed. The article quotes Eric Topol, the director of the Scripps Research Translational Institute, as calling the development of Paxlovid “the fastest development of a small molecule drug, with clinical validation and high efficacy, in history—no less in the midst of a pandemic.” In a study of unvaccinated people, Paxlovid reduced the risk of hospitalization for Covid-19 by 89%, leading the FDA to issue an Emergency Use Authorization (EUA) for the drug last December. It is now recommended for people with mild to moderate symptoms of Covid-19 who are at risk for developing more serious illness.

         That impressive science makes the fact that the drug is, by all accounts, substantially underutilized, both perplexing and disturbing. The situation is highly reminiscent of what happened when the vaccines were first rolled out for Covid-19 under FDA EUA rules: brilliant science leading to a safe and effective vaccine in record time and then profound difficulties getting it into the arms of people in the U.S. and around the world. The roll-out of Paxlovid in the U.S. appears to be another story of dysfunctional healthcare and science communication systems.

         Vaccines are highly effective at reducing the risk for serious illness, hospitalization, and death from Covid-19, but especially since the emergence of the Omicron variant it is clear that highly infectious mutants can readily infect even vaccinated people. More vulnerable people, especially the elderly, the immunocompromised, and those with underlying medical conditions like diabetes, are then more likely to develop significant symptoms. Developing drugs that can treat infected people and reduce the risk for this slide into serious illness has been a priority for scientists and pharmaceutical companies. One strategy is to administer antibodies specific to the virus that causes Covid-19, called monoclonal antibodies, as soon as someone is infected, but those require intravenous administration and therefore are not ideal.

         Two oral medications have been granted EUA for preventing serious illness in people who have been infected with Covid-19, Paxlovid and molnupiravir, but the latter does not appear to work as well as Paxlovid. (We are breaking our usual policy and referring to Paxlovid by its brand name because it is not available as a generic drug and its generic name—nirmatrelvir with ritonavir—is a tongue-twister that almost no one seems to be using yet). Paxlovid is a combination of a drug invented by the Pfizer company (nirmatrelvir) and an older drug used to treat HIV infection (ritonavir). They are both in the category of medications called protease inhibitors, drugs that block a virus’ ability to assemble itself inside a human cell and then replicate.

Paxlovid is an orally administered antiviral drug that has proven highly effective in preventing serious illness in people infected with the virus that causes Covid-19 (image: Shutterstock).

         If Paxlovid is so effective at preventing serious Covid-19 illness, then why isn’t it being widely used at a time when ever more infectious variants seem to be spreading? There are multiple reasons for this failure that fall into three main categories: 1. Lack of drug distribution, 2. Lack of awareness by the public, and 3. Lack of awareness and unwillingness to prescribe it by physicians.

Initial Distribution of Paxlovid was Problematic

         In her New York Times article “Covid drugs save lives, but Americans can’t get them,” Zeynep Tufecki detailed on April 22 the travails people have gone through to find a pharmacy stocked with Paxlovid. Some pharmacies had no Paxlovid while others had stocks of unused doses. “Social media is also replete with stories of despondent patients unable to locate doses or managing to do so after much effort and paying extra when they ended up out of their insurance networks,” she wrote.

         At the end of April, the Biden administration announced it would take a series of steps to increase the availability and use of Paxlovid, but that was four months after the EUA had been issued. It is still unclear why it has taken so long for Paxlovid to become widely available in hospitals, clinics, and pharmacies. The problem could rest with how much was initial manufactured and distributed by Pfizer or with the supply chain that links pharmaceutical companies to pharmacies. It is also unclear why it took federal and state governments so long to make a concerted effort to get Paxlovid to pharmacies. This all needs to be investigated because it seems absurd that a drug this effective should languish for four months off so many drug store shelves.

Public Poorly Informed about Paxlovid

         But even as Paxlovid does become more available, people may not know enough about it to ask for it or know how to access it.  Paxlovid must be prescribed by a physician, nurse practitioner, or physician’s assistant, and it needs to be taken within five days of first exhibiting symptoms. Not all Americans have such relationships with prescribers or even if they do are able to get through to them fast enough to make taking Paxlovid possible. Furthermore, because Paxlovid is not an FDA-approved drug yet but rather only available under the EUA program, Pfizer is not allowed to advertise it, either to the public or to prescribers. That leaves it up to local, state, and national public health authorities to ensure that people know that a pill is available that they can take to prevent serious illness if they develop symptoms and test positive for Covid-19. In some places, like New York City, frequent television ads about drugs to treat Covid-19 are appearing, but this is not the case throughout the U.S., and we are unaware of any systematic CDC or FDA programs to inform the public about it. Thus, the disjointed American healthcare system has not been able to provide sufficient public information about Paxlovid or to come up with a viable plan for getting it to people who need it.

Prescribers are Reluctant to Prescribe Paxlovid

         The prohibition against drug company advertising about Paxlovid extends to prescribers. As Tufekci notes “In the United States, such doctor outreach is often, sadly, left to pharmaceutical companies, which spend tens of billions of dollars each year marketing their drugs to physicians. This has led to heavily promoted drugs getting prescribed even when cheaper, effective alternatives exist.” Once again, there has been a lackluster attempt on the part of public health agencies to educate physicians and other prescribers about Paxlovid. Our healthcare system appears content to default to drug companies to provide physicians with information they need about newly available medications.

         This lack of prescriber education about Paxlovid may explain one of the main reasons physicians appear to be reluctant to offer patients the medication: what are called drug-drug interactions. Most medications we take are broken down (that is, metabolized) by the liver, thus controlling how high the blood levels of the drug can go. The liver has a set of enzymes called the cytochrome P450 system that is responsible for metabolizing drugs. The activity of these enzymes is controlled by our genes, so that activity varies from one person to the next depending on the individual’s genetic make-up. Some people are faster metabolizers of specific drugs than others.

         Some drugs we take can inhibit the activity of these metabolic enzymes, and Paxlovid is one of them. Its ritonavir component inhibits an enzyme called 3A4 in the cytochrome P450 system, making metabolism of a host of other medications less efficient. That means that there are many drug interactions with Paxlovid that can lead to significant increases in blood levels of certain medications. Since elderly people are considered among the important candidates to take Paxlovid and they are most likely to be taking multiple other medications, prescribing Paxlovid can be tricky.

         A doctor or other prescriber about to give someone a prescription for Paxlovid may see the long list of potential drug-drug interactions and become wary. Some of the medications that interact with Paxlovid might be stopped for the five days a person takes Paxlovid, but others, like drugs to control heart rhythm disturbances such as atrial fibrillation, cannot be stopped so easily. There are probably ways to handle these situations (such as temporarily lowering the dose of a drug with which Paxlovid interacts), but prescribers have not been given sufficient information about what to do in such instances and we hear anecdotally that this is discouraging some physicians from prescribing it. How widespread a reason this is for the lack of Paxlovid uptake is unknown at present, but again speaks to the failure of public health agencies like CDC and FDA to conduct timely and meaningful prescriber education campaigns.

         On three levels then—supply, public information, and prescriber education—our healthcare system has failed to get Paxlovid into the hands of people who should take it. This is another example of the shortcomings of the American healthcare system, a system that is based on some of the world’s most outstanding biomedical research but nevertheless routinely fails to make the progress of modern science available to its constituents. In the case of Paxlovid, we see a disjointed drug distribution system and a failure of vital health science communication to both the public and healthcare providers. We also see the results of years of default to pharmaceutical companies for critical public health education to both groups.

         The Paxlovid story is a case in point, then, of some of the things that are wrong with the American system. What should have happened was three-fold. First, the moment Paxlovid was first presented to FDA for an EUA, federal authorities should have planned for the drug’s rapid distribution to pharmacies and hospitals around the country. Second, federal, state, and local public health agencies should have developed a comprehensive plan to provide the public with information about Paxlovid, including who should take it and where to get it. Third, the same public health authorities, along with medical and nursing associations, should have developed an education campaign aimed at prescribers, informing them about the benefits of prescribing the drug and providing them with algorithms for what to do in complex situations such as those that arise because of drug-drug interactions. Once again, we have witnessed the benefits of great science vitiated by poor public science communication.

Are Popular Personality Tests Accurate?

Here’s what we do and don’t know about Myers-Briggs.

It’s common in many workplaces these days to encounter some kind of personality or “work style” assessment. Many employers ask employees to take these assessments to get a better sense of optimal work settings and workflows for individual employees. For example, naturally introverted employees might do better doing primarily internally-focused research and desk work while someone who is naturally more extraverted might have an easier time working in sales, marketing, or any kind of external-facing work that involves contact with a variety of partners.

The Myers-Briggs Type Indicator is a personality inventory that categorizes people across four domains: introverted versus extraverted; sensing or intuition; thinking or feeling; judging or perceiving. People’s preferences and personality profiles can thus be summed up along these four domains; for example, an INTJ would be someone whose proclivities line up most with being introverted, intuitive, thinking, and judging. While the Myers-Briggs inventory is by no means the only kind of personality or work style inventory that is used in the corporate world (many new assessments have cropped up over the years), it is a very commonly used instrument when people are trying to figure out their general preferences.

Yeexin Richelle/Shutterstock
Source: Yeexin Richelle/Shutterstock

But is Myers-Briggs reliable from a scientific perspective?

The test might be popular and pervasive (many readers will have heard of it, and some have probably taken it more than once), but there is some pretty lively debate about whether it is a reliable and accurate instrument. From a purely anecdotal perspective, it is easy to see where there might be considerable flaws in the test. For one thing, we know people who have taken the test once and then taken it again a few weeks later and scored very differently on certain items.

In addition, it is hard to know how to interpret a score that is on the border between two types. For example, it is possible to score right in the middle between being extraverted and introverted. What exactly does this mean, then? It is not clear how to use this kind of information.

2018 article in Scientific American offered a relatively harsh view of Myers-Briggs and other personality tests. Among the problems already noted about the test, experts also argue that the questions are confusingly worded, thus making it difficult to know whether people are interpreting the questions in the ways they were intended. In addition, most personality tests were invented in the first half of the 20th century on the basis of researchers’ subjective feelings about the most important components of personality. The result is a wide variety of tests that are not based on solid academic theory about what comprises the most important aspects of a person’s preferences and personality.

In a more recent article in Psychology Today, Dr. Aqualus Gordon argues that claiming the Myers-Briggs has been “debunked” is going a step too far. He argues that calling it pseudoscience is unfair since rigorous academic studies of its efficacy have not been performed. He also points out that people often expect the assessment to predict things that it is not set up to predict, such as job performance. The assessment has a lot more to do with preferences and job satisfaction than with actual performance. Predicting job performance is undoubtedly outside the purview of the Myers-Briggs, but expectations that the assessment can serve this function might lead to more skepticism of the instrument. Furthermore, it is unclear whether the test even does what is within its purview, such as accurately predicting job satisfaction.

Key takeaways

Until we more rigorously study the Myers-Briggs, we cannot make claims about its efficacy or accuracy. Psychometric scales need to be subjected to rigorous validation tests, which it is clear this test has not. Most other personality tests have not been subjected to this kind of validation either. If we want the scientific community to take these tests seriously and advocate for their use, they do need to be properly validated. In the meantime, it probably does no harm to take some of these tests for fun just to get a better sense of how one scores. But putting great stock in their results and making major career decisions based on them may not be warranted without more thorough engagement with the science of psychometric validation.

Primary Care in the U.S. Falls Short

About three-quarters of Americans have a primary care physician. Having a primary care doctor is associated with better health outcomes. As we have previously noted, Americans tend to trust their primary care physicians more than most other sources of healthcare information.  

         All of this should mean that it might be a wise move to extend primary care to more people and to ensure that primary care doctors have enough time to spend with their patients to take advantage of that trust and help them navigate the many pathways to optimal health outcomes.

In fact, however, according to a recent report from the Commonwealth Fund, the U.S. is failing at providing high-quality primary care compared to other high-income countries. The report is based on surveys the Fund conducted in 2019 and 2020 with primary care physicians in the U.S. and 10 other high-income countries. Among the findings are:

·  U.S. adults have nearly the lowest likelihood of having a regular doctor or place to go for care (Sweden was slightly lower).

·  U.S. adults are the least likely to have a long-standing relationship with a primary care provider (43% versus 71% of adults in the Netherlands or 57% in Canada).

·  U.S. adults are least likely to be able to see a primary care provider after regular office hours

·  Primary care physicians generally do not screen their patients for social needs, but here U.S. doctors are the most likely to do so (30%). The authors of the report speculate, however, that this may be because the U.S. has the poorest social services networks for its citizens, creating a greater need for such inquiries. Only Canadian primary care providers are more likely to have social workers in their practices (42% versus 37% in the U.S.).

·  Only one-third of U.S. primary care physicians have mental health providers in their practices. This is about midway among the countries in the survey, with nearly all practices in Sweden and the Netherlands having mental health providers in their practices, but almost none in Germany, Switzerland, or Norway.

·  Only half of U.S. primary care providers report adequate levels of coordination with specialists and hospitals about changes in their patients’ care plan, putting the U.S. near the bottom in this category. Similarly, only half of U.S. primary care providers are notified when their patients are seen in an emergency department, compared to 85% and 84% in New Zealand and the Netherlands, respectively.

Overall, then, the report makes clear that the U.S. is doing a poor job at primary healthcare. Importantly, the report notes that these shortcomings in U.S. primary health care are not distributed evenly but “affect predominantly Black and Latinx communities and rural areas, exacerbating disparities that have widened during the COV ID-19 pandemic.”

What Do People See Primary Care Providers For?

         An average visit with a primary care physician lasts 18 minutes. According to a Mayo Clinic study, these are the top ten reasons for those visits:

  • Skin disorders;
  • Osteoarthritis and joint disorders;
  • Back problems;
  • Cholesterol problems;
  • Upper respiratory conditions, excluding asthma;
  • Anxiety, depression, and bipolar disorder;
  • Chronic neurologic disorders;
  • High blood pressure;
  • Headaches and migraines; and
  • Diabetes.

Now let’s look at the top causes of preventable premature death in the U.S. This list is topped by tobacco smoking and includes obesity, alcohol use, hypertension, some infectious diseases for which vaccinations are available, firearm injuries, and suicide. In the 18 minutes that a primary care doctor has with a patient, how much time is spent dealing with these preventable causes of premature death? Take cigarette smoking, for instance. We know that relatively brief primary care interventions can have a significant effect on increasing the chances that a smoker will quit. The same is true for harmful alcohol consumption. Primary care physicians may themselves be surprised to learn that their paying attention to their patients’ weights can influence obese patients to attempt weight loss, a practice that may be helpful for many people with high blood pressure or diabetes. We can also wonder about the potential impact on mental health and suicides if more primary care practices had mental health practitioners within them.

Primary care is at the heart of all healthcare systems, but it is inadequate in the U.S., with primary care doctors having inadequate time and resources to deal with the things that affect their patients’ health (image: Shutterstock).

Do primary care physicians have time to talk to patients about their lifestyle and behavioral issues? Do they keep careful track of their adult patients’ vaccination status? When a patient circles “yes” on the pre-visit form about cigarette smoking, does the doctor recognize that even a few minutes spent talking about options for quitting can save more lives than almost anything else the doctor can do?

U.S. Primary Healthcare Needs an Overhaul

It is clear we need to fix the primary healthcare system in the U.S. Right now, it is a disorganized system that disadvantages people of color. It is also unprepared to deal with the factors that are clearly responsible for most people’s adverse health outcomes. Treating rashes, upper respiratory infections, and backaches is important, but primary care clinicians could have far more impact on the public’s health if they also dealt with tobacco and alcohol use, obesity and lack of exercise, and vaccine hesitancy. Furthermore, their practices would become far more impactful if they included mental health providers to deal with common psychiatric conditions like anxiety disorders and depression and social workers to help with the social determinants of health like food and housing insecurity.

The U.S. clearly has a long way to realize any of these goals. As Kevin Grumbach and co-authors wrote in their September 2021 New England Journal of Medicine article “Revitalizing the U.S. Primary Care Infrastructure”:

More than half of office visits in the United States are to primary care clinicians, yet primary care physicians make up only 30% of the physician workforce and are supported by only 5.4% of national health expenditures, and research on primary care garners just 1% of federal agency research awards.2 One in five Americans live in a federally designated primary care Health Professional Shortage Area. Primary care physicians earn 30% less than other physicians, on average, and they have among the highest rates of physician burnout.3

         In its sweeping 2021 report on rebuilding the U.S. primary health care system, The National Academies of Sciences, Engineering and Medicine noted that “The value of primary care is beyond dispute” but at the same time “this foundation remains weak and under-resourced.” Clearly, the first order of business in repairing our crumbling primary healthcare system is to fund it adequately. This is perhaps easier to do in countries that have rational, single-payer healthcare systems (as is the case in all high-income and many middle- and low-income countries, but not the U.S.). What we need, and what the National Academies endorse, is a major rethinking of how we finance medicine.

Instead of spending time discussing their patients’ health and risk factors for disease, primary care doctors face increasing bureaucratic demands that are uncompensated and contribute to high burnout rates (image: Shutterstock).

         Right now, the highest paid medical specialties are mostly surgical. Primary care physicians are way down on the list. If someone does choose a career in primary care medicine, they will be faced with having to see large numbers of patients for short periods of time, day in and day out. There will be endless hours logging all these patient encounters into the electronic health record (EHR), most of which gets done after hours and without compensation. No wonder we have a shortage of primary care physicians and those that do enter the field suffer high rates of burnout. The first order of business, then, in repairing the primary care system is to compensate primary care providers better and make primary care a desirable medical specialty.

         Next, we must compensate those primary care practices to be able to spend enough time with patients to accomplish a public health mission: the prevention of disease. That means not only asking patients to fill out questionnaires about their health and habits (many of which seem never to actually get read by any health professionals) but having the time to actually deal with the responses. If someone smokes, is drinking alcohol excessively, is eating a high sugar diet, or is hesitant to have a flu vaccine, the doctor or another health professional in the office needs to address that problem using evidence-based approaches. The healthcare system must be prepared to pay people to do that.

         All of this will require training primary care physicians, nurses, social workers, and other healthcare providers in a new paradigm of care, one in which attending to the real causes of diseases and the impediments to successfully overcoming them is of paramount importance. For example, primary care physicians must be trained in techniques like motivational interviewing and other evidence-based approaches to helping patients with substance use issues. A mental health clinician trained in cognitive behavioral psychotherapy for depression and anxiety should be part of every primary care practice. Patients who need to lose weight or exercise more should be given help, encouragement, and follow-up support by people they trust, that is, by their primary care doctor. Primary care offices should have social workers who can assist patients in getting assistance with housing, food, and health insurance. We know that doing these things works to prevent disease, but we are stubbornly unwilling to implement them. That needs to change.        

Our primary healthcare system is broken and because of it, Americans are missing out on the chance to benefit from a great deal of science telling us how to prevent many diseases and premature deaths. Fortunately, there is now widespread agreement that funds must be directed toward a bold revamping of how we deliver primary care.

Mental Health Emerges As A Major Issue During the Pandemic

From nearly the beginning of the Covid-19 pandemic, experts in psychology and psychiatry worried that there would be major increases in the number of people with mental health issues and diagnoses. Evidence now supports that those worries were well-founded, and the situation has been called a pandemic mental health crisis. Studies find clear increases in anxiety and depression in both adults and children and last December the U.S. Surgeon General, Vivek Murthy, issued an advisory on the youth mental health crisis that he noted has been exposed by the pandemic. Unsurprisingly, given the disproportionate impact of the pandemic, communities of color have been especially affected by the mental health consequences of Covid-19. Although suicide rates appear not to have increased in the American population overall during the pandemic, they are rising among Black, Latinx, and Asian American people. Suicidal ideation and attempts have increased in some groups, including adolescent girls

         Equally disturbing as the rise in mental health problems during the pandemic is the failure to provide increased access to mental health services. Although telehealth applications may be improving access to mental healthcare for some people, there is still a shortage of mental healthcare providers in many parts of the world, including the U.S., and many people have restricted access to care due to lack of affordability and insurance coverage.

Is There a Broader Solution To the Increase in Mental Health Problems?

         Researchers have tried to figure out ways to improve access to care  for people with mental health conditions and our attention was recently drawn to one such study. Published in the Journal of the American Medical Association, investigators from several Kaiser Permanente health facilities randomized nearly 19,000 patients who had endorsed having suicidal thoughts to one of three conditions: a care management condition in which care managers sent messages to patients encouraging them to have outpatient care; an online version of an evidence-based intervention called dialectical behavior therapy (DBT); or usual care. All the participants were free to also receive care in the usual way from the Kaiser Permanente system, but only those in the first two groups were offered additional care as well. The hope was that making proactive outreach attempts to people with a mental health issue, rather than relying on them to take the initiative to get help, might improve outcomes and reduce suicides and suicide attempts. The study was funded by the National Institute of Mental Health.

         The results of this large and rigorously conducted study were disappointing. Neither additional intervention decreased the number of serious suicide attempts or deaths by suicide compared to continued usual care. In fact, the patients randomized to the shortened version of DBT had more suicidal events than the usual care only group, a finding we believe was probably a fluke.

         Why would offering additional care to people suffering with suicidal thoughts not be helpful? There are several possibilities, many acknowledged by the authors of the study. One is that attrition from both outreach interventions was very high, with only 30% to 40% of people invited to actively engage with the interventions actually participating. Furthermore, it could have been that usual care provided to all the study participants was maximally effective, creating a ceiling effect whereby any additional care would not be able to make a difference

         Another important limitation of the study was described by the study authors as follows: “The care management intervention tested in this trial was a low-intensity program delivered by online messaging with rare telephone contacts and no in-person visits.” Similarly, the DBT intervention was done online and involved only a portion of the elements usually incorporated into a DBT intervention for people with suicidal ideation. The authors point out that there is evidence from previous studies that these interventions might work, but one wonders if it would have been possible to do a much smaller study first to see if they worked with this particular design. With almost 19,000 people randomized, the study must have required a substantial amount of federal funds to run.  While there is never any guarantee that a research study will yield positive results and the journal is to be commended for publishing a study with negative results, it still might have been prudent to do some exploratory work before launching into such a major undertaking.

         This is particularly true because one might have anticipated that offering watered-down versions of mental healthcare would not be effective. Dialectical behavior therapy (DBT), for instance, has been shown in multiple studies to be an effective treatment for several conditions, but it is unclear that the online version used in the study would work as well.  Shouldn’t that have been tested first? While it is understandable to want to provide help for as many people as possible at a time when mental health access is so difficult, it may be inadvisable to rush into offering diluted versions of evidence-based interventions to achieve that goal.

No Shortcuts to a Solution

         The solution to the mental healthcare access problem—and thereby to the increase in mental health issues so many experts say we are facing—is to figure out how we can deliver the evidence-based interventions we already have to more people. For people with anxiety disorders, depression, and posttraumatic stress disorder (PTSD), there are both evidence-based psychotherapies, like cognitive behavioral therapy (CBT), and antidepressant medications that have proven effective. We doubt that anyone would contemplate reduced dose studies on such a large scale of proven medications for the treatment of other medical conditions like diabetes, heart disease, or cancer without some at least preliminary evidence that this might be effective. Why then do we assume that this is a good strategy for mental health disorders? 

Many reasons for the current rise in mental health conditions have been advanced. Worry, loss of sleep, and economic strains from job losses are all posited factors. The pandemic has highlighted the huge disconnect between the scope of mental health problems and the availability of mental health interventions in this and many other countries. We need to join with the Surgeon-General’s call to work much harder to bridge that gap. It will probably require providing sufficient funding to allow people to engage with psychiatrists, psychologists, and other behavioral health professionals, both via telehealth and in person, using the tools we already know are effective. Attempts to find broader solutions to the treatment gap should be careful not to assume that diluted versions of those tools are going to be effective because shortcuts to solve the mental health crisis may well not work. We need to educate primary healthcare providers about how to recognize and treat mental health illnesses; train and deploy an adequate number of psychiatrists, psychologists, and therapists; provide appropriate insurance coverage for mental health needs, including better enforcement of already on the books mental health parity laws; and initiate better public health campaigns to educate people about the signs of mental health problems and their proven solutions. Doing this will be money well spent.

Building Trust Amid Uncertainty

Sometimes It Is Best To Say, “We Don’t Know”

In what was without a doubt a scientific triumph, scientists sequenced the genome of the new virus causing a rapidly spreading pandemic and then harnessed a new technology involving messenger RNA (mRNA) to bring us vaccines that dramatically reduce the risks of our getting severely ill or dying from it.

         The above statement is the accurate way of looking at what happened in the first year of the coronavirus pandemic. How is it possible, then, that a Pew Research Center report issued on February 28 tells us that “fewer U.S. adults are confident that scientists are acting in the public’s best interest than before the pandemic began.” The report showed that between April 2020 and December 2021 the percentage of Americans who have a great deal of confidence that medical scientists act in the best interests of the public declined from 43% to 29%.

         There is clearly a huge disconnect here between what scientists have accomplished during the pandemic and how people view their work. That means there is major work ahead of us to understand what caused that lack of trust and to repair it. Fortunately, many scholars and policymakers are examining the problem and recommending steps for us to take to improve the situation.

Uncertainty Drives Mistrust

         A driving force behind the growing lack of trust in medical scientists seems to stem from the discomfort some of us have with uncertainty.  James Dillard, a communication scientist at the Pennsylvania State University who studies warning messaging, recently explained that “Pro-vaccine messaging is taking place in a highly competitive message environment—one that involves active efforts to undermine public health advocacy…The fact that scientific knowledge evolves and always possesses a degree of uncertainty explains why health agencies change—and continue to change—their messaging. Regrettably, this inconsistency also undercuts the impact of health messaging in a public that wants simple, consistent answers.”

It turns out that we vary in how much uncertainty we can stand and that many factors determine that variability. “As intolerance of uncertainty has begun to be studied as a separate trait from a tendency to worry, “writes Francine Russo in Scientific American, “psychologists have identified typical behaviors—often unconstructive ones—that people use to tamp down their distress at not knowing…Some collect every bit of information they can find online and offline.” If scientists appear uncertain, in part because they change their recommendations based on evolving information, then people with high uncertainty avoidance will seek certainty elsewhere, putting their trust in sources that seem confident even if we know them to be misleading or incorrect. 

Russo describes a study conducted at the University of Illinois, Chicago two years before the coronavirus pandemic in which neural activity during an uncertainty test was measured using functional magnetic resonance imaging. Two years later, participants in the Chicago study  who manifested high activity in a brain region called the anterior insula during the uncertainty test reported increased anxiety, depression, or emotional distress during the pandemic. The anterior insula is associated with unpleasant emotions and fear and this finding suggests that there is a biological trait linked to discomfort with uncertainty.

Lack of trust in health authorities may also have deep roots. A recent study from the U.K. showed that a history of childhood trauma predicted COVID-19 vaccine hesitancy and was independently associated with low levels of trust in National Health Service information about COVID-19. Any attempt to improve our trust in medical science must therefore take into consideration these traits, some of which are inherent in our makeup, some of which are cultural, and others acquired by the often traumatic experiences we have through our lives.

Acknowledging Uncertainty

Borrowing from their research in child development, scientists Tamar Kushnir, David Sobel, and Mark Sabbagh recently wrote that “Research suggests that people are more likely to follow advice delivered with confidence and to reject advice delivered with hesitancy or uncertainty.” When, however, that advice changes, as it has frequently and inevitably during the pandemic, the uncertainty created in peoples’ minds leads to decreased trust in the advice-givers. Their work suggests a solution. “Our research suggests that, in many cases people trust those who are willing to say ‘I don’t know.’”  They go on to assert that:

“The good news is that, based on our research, we believe the human mind doesn’t balk at hearing communicated uncertainty – quite the opposite. Our minds and brains are made to handle the occasional ‘I think so,’ ‘I’m not sure’ or ‘I don’t know.’ In fact, our ability to do this emerges early in child development and is a cornerstone of our ability to learn from others.”

It may not be uncertainty alone, then, that is so discomfiting to us but rather the illusion of certainty that is breached by overly confident health officials that most unnerves our trust in them. What follows from this is that we need a massive campaign to train scientists and health authorities about how to communicate uncertain science without undermining confidence in science. Just as important, we need to educate people how to live with that uncertainty. It will be crucial to ensure that this work is culturally sensitive as well, as the ability to tolerate uncertainty differs not only among individuals but among cultural groups as well. Scientists need to be able to say “this is what appears to be the case from the work we have done so far and therefore we are making recommendations based on what we know now. More research will be done, and these recommendations may change as new information emerges. We’ll be sure to let you know right away when there is a new development.”

The effort to improve trust in scientists will take time. A Yale University research group led by Tauhid Zaman has developed a method of moving people away from online inflammatory ideas that “begins with an attempt to build trust over time,” a tactic he calls “pacing and leading” that is played out over months. “I come close to you,” Zaman explains about his work with people expressing uncivil attitudes about things like immigration on Twitter, “and then I take a step. I start to pace you and lead you somewhere else.” He has expressed the belief that his slow and steady approach to building trust with people online will also work in the public health arena. About COVID-19 vaccines, for example, he says:

“I think public officials’ approach to persuasion about the vaccine has been totally misguided. There are people who don’t want to get the vaccine, and the response has been to tell them it’s good and jam that message down their throats. That’s just going to create more antagonism, more skepticism, more denialism. Persuasion takes time; it’s not instantaneous.”

         A similar approach to regaining trust is followed by astronomer Katie Mack of North Carolina State University. “What I try to do is share the real information, and I try to share it in a nonjudgmental way. When people ask me a question, and they have a misunderstanding, I try to correct that misunderstanding in a way that doesn’t imply that they’re dumb to believe it in the first place. I try to start from the point of, ‘it’s great you’re interested in learning more about this. Here’s how you can learn more about it.’”

         Last February New York Times columnist Ezra Klein put the issue bluntly. “Public health is rooted in the soil of trust. That soil has thinned in America.” Klein cited a recent paper in the journal Lancet that examined the relationship between trust in government and fellow citizens and COVID-19 infection rates in 177 countries. “This yields the paper’s most striking finding,” Klein wrote. “Moving every country up to the 75th percentile in trust in government…would have prevented 13 percent of global infections. Moving every country up to the 75th percentile of trust in their fellow citizens…would have prevented 40 percent of global infections.”

         Mistrust in government, public health authorities, and medical scientists has a real effect on our individual and collective health. It stems in large part from an inability to accept the uncertainty inherent in science and is worsened by communications from health authorities that are overly confident and that do not prepare us for the inevitable changes in guidance that result from newly emerging research. We need to think of trust as a public good, something that governments are in large part responsible for maintaining and, when necessary, repairing. It will take an understanding of the many factors that impinge on the tendency to uncertainty intolerance and of the ways we form and maintain trust in institutions and authorities. It will also take time, patience, and an empathic stance. Ignoring the growing issue of mistrust in public health institutions and medical science would be to put the public’s health in ever graver peril.

What Are the Odds?

How We Know What A Diagnostic Test Means

Mary, a healthy 30-year-old woman, wakes up one morning with a stuffy nose and a scratchy throat. She has been very careful about wearing her high-quality, N95 mask in public places and has had three shots of an mRNA vaccine against the virus that causes Covid-19. Still, she knows that even vaccinated people can become infected, so she does a home Covid-19 test on herself and it is negative.

         Mary has heard, however, that the rate of false negatives for the home tests, which detect the presence of a protein (also called an antigen) on the surface of the virus, is very high. She worries that despite the negative test she may actually be infected with SARS-CoV-2, the virus that causes Covid-19, so she seeks out a PCR test. The PCR, or polymerase chain reaction, test for the virus, she has heard, is more accurate but can take several days to get a result. She goes to a local pharmacy, gets the nasal swab test, and goes home to wait for the result. Her symptoms continue to worsen.

         Three days later Mary gets a text telling her that her PCR test is negative. She is pretty sure this means that she does not have Covid-19, but she now has a bad cough, some chest pain, and a very sore throat. She decides to visit her primary care physician. Her doctor agrees that it is unlikely she is suffering from Covid-19, asks questions about her symptoms and her medical history, and performs a physical examination. Her lungs sound clear, and the doctor finds no abnormalities on the examination. Blood tests, a throat culture, and a chest X-ray to rule out pneumonia are ordered.

         The next day, Mary gets a call from the doctor that her X-ray was normal but one of the blood tests of liver function the doctor ordered has yielded a slightly elevated level.  Mary is perplexed by this—she has no symptoms other than what now appears to be an upper respiratory viral infection. She does not drink excessive amounts of alcohol and has had only one sexual partner for many years. Why should she have an abnormal liver function test? Could it be a false positive? Should she see a liver specialist and have more tests?

How to Interpret Laboratory Tests

         This not uncommon situation raises the issue of how we interpret the myriad of laboratory and imaging tests doctors now have at their disposal to help make diagnoses. We would like to believe that the results of these tests have easy, cut-and-dry interpretations, either positive or negative for a disease. In fact, no laboratory test is perfect, false negatives and false positives occur with all of them, and even the decision about whether to order a test in the first place depends on many factors.

Diagnostic test results may give “positive” or “negative” results, or said to be “normal” or abnormal,” but their meaning is usually not so black and white. Several considerations are important in deciding whether to order laboratory tests in the first place and, if they are ordered, in understanding what the results mean (image: Shutterstock).

         An article in The New York Times last January highlighted an extreme version of the difficulty sometimes encountered interpreting diagnostic tests. Titled “When they warn of rare disorders, these prenatal tests are usually wrong,” the article details the perils of tests performed on blood samples from pregnant women that are intended to reveal whether a fetus will be born with a genetic disorder. The analysis of these tests by The New York Times investigative reporters showed that “the positive results on those tests are incorrect about 85 percent of the time.” The article tells the harrowing story of people who were told on the basis of these blood tests that their unborn child would suffer from severe genetic abnormalities and is rightly critical of the industry that performs and promotes these tests. “The Times reviewed 17 patient and doctor brochures from eight of the testing companies,” the reporters wrote. “Ten of the brochures never mention that a false positive can happen. Only one mentioned how often each test gets positive results wrong.”

         While it is obviously unacceptable to withhold information from prospective parents shelling out hundreds or thousands of dollars for these tests, which give false positive results most of the time, what The New York Times article did not explain is that none of this is at all a surprise to people who understand how diagnostic testing works. The accuracy of any diagnostic test depends not only on the accuracy of the test itself, on multiple other factors including how common the illness is in any population (that is, its prevalence) and something called “pre-test probability.”

Specificity and Sensitivity

         The accuracy of any diagnostic test can be measured in several different ways, most basically with metrics called specificity and sensitivitySpecificity refers to the ability of a test to detect someone who does not have the disease in question. A highly specific diagnostic test will yield very few false positive results. The specificity of the PCR test for Covid-19 is very high, around 95%, so that if you have a positive test you are very likely to really be infected. The sensitivity of a test refers to its ability to detect some who does have the disease. A highly sensitive diagnostic test will yield very few false negatives. The sensitivity of the PCR test for Covid-19 is also very high, around 90%, so that if your test is negative you most likely aren’t infected. Home Covid-19 tests are also quite specific, but not as sensitive so that Mary was correct that her negative test could have been a false negative and she did the right thing to seek a PCR test to be sure.

         When testing for very rare diseases, however, as is the case with the prenatal tests discussed in The New York Times story, even very specific tests can yield many false positives. An article in ProPublica noted by Critica Chief Medical Officer Dr. David Scales gives a good explanation of why this is the case. It gives the example of a disease that is present in 4% of the population. If 1000 people are screened and the test is 100% sensitive (note that almost no real tests are this sensitive), it will accurately detect all 40 people who truly have the disease. Let’s say that the test is 95% specific. That means that 5% of the remaining 960 people who don’t actually have the disease—48 people—will nevertheless test positive. The number of false positives thus exceeds the number of true positives in this example, even with a test with very high specificity and sensitivity. The genetic syndromes The New York Times article was concerned about are much less common than even 4%–occurring in some cases at rates of around 0.05% of the population or even less. It is obvious, then, that no matter how accurate the diagnostic test is, there will be more false positives than true positives with a screening test for diseases this rare. A negative result on one of these prenatal tests may be reassuring, but a positive test is hard to interpret and obviously will cause a huge amount of anxiety in the prospective parents, who will have to wrestle with decisions such as whether to continue the pregnancy, undergo more invasive diagnostic tests, or even just ignore the blood test result. Testing companies should be much more upfront informing people about the real-life accuracy of these prenatal tests, but no one should be surprised that positive results will usually be false.

Pre-test Probability

         One thing that can help sharpen diagnostic decision making is to consider the pre-test probability that a person has an illness. Before ordering any test, it is important to consider two things: how likely is it that the person has the illness in question and will the test result make any difference in the patient’s life. The first of these considerations is the pre-test probability. In Mary’s case, there was a reasonable pre-test probability that she had Covid-19 because she had typical symptoms of the illness: nasal congestion, cough, and sore throat. This makes her negative result on the home Covid-19 test more reassuring, because false negatives are more common in asymptomatic people.

On the other hand, Mary’s history and physical examination results make it very unlikely that she has liver disease. Were it not for the fact that she came to the doctor because of nasal stuffiness and cough, no blood tests would ever have been ordered. She has no risk factors for liver disease and on examination her liver was not enlarged. Many physicians would not have ordered liver function tests in this case in the first place.

         Now faced with an abnormal laboratory result, Mary and her doctor can apply an algorithm that takes into account the pre-test probability of liver disease and the accuracy of the laboratory test. We won’t go through the mathematics of that here but suffice it to say that applying the algorithm yields a very low percentage likelihood that Mary actually has any problem with her liver. The post-test odds of disease, then, are very low and Mary and her doctor conclude the test result is most likely a false positive (the magnitude of the abnormality of the liver test, which was small, is also a factor here that we haven’t discussed). They decide to ignore it and repeat the test in a few months just to be sure. Other patients and doctors may choose a different course of action, but the important thing is that once again there is no black and white about the blood test result. A “positive” test result in this case does not mean that Mary has liver disease.

         It was not that long ago that doctors had few diagnostic tests at their disposal and had to make diagnoses based mainly on history, physical examination, and intuition. There is no question that more sophisticated laboratory methods and new diagnostic tests have improved the accuracy of diagnoses and patient outcomes. But there is also recognition that many tests are ordered unnecessarily.  Before a test is ordered, some considerations are:

1. How accurate is the test—what is its sensitivity and specificity? How likely is a false negative or false positive result?

2. What is the pre-test probability that an illness is actually present? What effect would a positive test result have on the post-test odds that an illness is present?

3. What difference will the test result make? Will it alter management of an illness, provide reassurance, change plans?

Before you ask your doctor to order a blood test or an MRI scan, then, ask them to discuss those three considerations with you. It might be that you and the doctor will decide that the test is unnecessary. At the very least, you’ll be in a better position to understand what the test results mean if you do go ahead with it. Had Mary known all of this, she might have asked her doctor what all the blood tests they ordered were, what they were for, and why they were being ordered. Perhaps, with that information, the liver test would never have been done at all.

What Journalists Write Matters

Is There a “Do No Harm” For Reporters and Editors?

At graduation, physicians recite the Hippocratic Oath, some versions of which include the famous injunction “Primum non nocere” (First, do no harm). It is not the case, however, that only healthcare professionals need to remember this warning.

         Last December 9 and then again on February 4 The New York Times published two articles that are causing a stir in the world of suicide prevention and research (note that Critica will not post links to either article for reasons that will become clear). The first article detailed a website that gives advice on how to kill oneself and the second tells readers about a chemical that can be bought online that is increasingly used by people trying to kill themselves (again, Critica will not list the name of the website or of the substance). Between these two articles, a piece appeared online in Medium by four academic suicide researchers titled “The New York Times might have increased suicide deaths. Here’s what it can do to fix it.”

In two articles, The New York Times gave details about a website that promotes suicide and a means of attempting suicide. Did it violate guidelines for reporting on suicide and did its actions increase the number of suicides? (image: Shutterstock).

         The authors of the first Times article, dealing with the website, apparently worked for a year researching the site and uncovering cases of people who seem to have been motivated to kill themselves by it. It is accompanied by a warning, “This article focuses on suicide and contains details about those who have taken their own lives. If you are having thoughts of suicide or are concerned that someone you know may be, resources are available here.” But the article then goes on to explain in detail how to find the suicide-promoting website. We had no trouble finding it with a simple Google search and although the site says it is only for people over 18, there is of course no real way to prevent children from going on it. Once there, they will find postings by people seriously considering suicide and advice on how to take one’s life.

Uncovering a “Dark Corner” of the Internet

According to one report (again, Critica is not providing links), the Times authors considered the ethics of describing the website in detail because they felt compelled to bring to light a “dark corner” of the internet. If people are following the advice of this website and dying, then a thorough public investigation may be warranted to allow authorities to consider regulating it. The Times story identified 45 people whose deaths by suicide involved the website and noted that “The site now draws six million page views a month, on average—quadruple that of the National Suicide Prevention Lifeline…” They decided to name the website in their story and the substance used in many of the suicides “in order to fully inform readers about the dangers they pose, particularly to the young and vulnerable.”

But the four suicide researchers who authored the Medium article remind us that “Decades of research have also shown that when news and entertainment media share information about suicide method and location, there is a short-term increase in suicide deaths.” Over 30 years ago Madelyn Gould and David Shaffer of Columbia University were among the first to show in an article in the New England Journal of Medicine that media depictions of suicide can lead to imitative suicide attempts. The New York Times named the website, gave many details about the people who had supposedly killed themselves because of the website, and named a means of attempting suicide that some of them had used. Critica is deliberately withholding links to the articles that do this because we believe the research showing that doing so can in fact lead to an increased risk for suicide among some vulnerable people.

Guidelines for Reporting Suicides

         That research by Gould, Shaffer, and many others has led to the development of suicide reporting guidelines, which, among other things, recommend against printing the method by which someone ended their life. This was clearly violated by the second New York Times story, which details a method apparently being used with increasing frequency and how to obtain it. Again, we had no trouble finding the substance on Amazon and could easily have purchased it.

         The Medium article authors, writing about the first of the two Times articles, stated that “While we were grateful that this investigation could lead to the website and the novel method being shut down, we were equally concerned that disregarding the suicide reporting recommendations could result in more suicide deaths.” The authors then urged The New York Times to conduct research to find out if in fact their articles are associated with an increase in suicides. “If the journalists and editors believe that publishing this piece was in the service of saving lives,” they wrote, “then it is imperative for them to follow through in the ways outlined…”

         Of note, the Medium article authors say that The New York Times refused to publish their article.  

More Reporting Guidelines are Needed

         When journalists write their stories, they are undoubtedly interested in getting a maximum number of readers. Some are also interested in producing work that will advance a public good. But do journalists and editors consider their potential to do harm? Reporting on suicide is one of the ways that journalists can indeed do harm, but guidelines that may minimize that harm are inconsistently followed. There is also evidence that reporting on mass shootings can encourage copycats and guidelines have been issued for better reporting of mass shootings as well. It would be interesting to learn the extent to which these guidelines are followed.

         During the Covid-19 pandemic, we have seen that misinformation about vaccines can lead people to delay or refuse getting vaccinated. Thus, we know that what people see and read influences their behaviors. Journalists and editors, therefore, must be aware of the potential they have for causing harm if they do not carefully think through the ways that they report about important health issues.

Imagine the following possibility: There is consensus among medical experts that high blood pressure (hypertension) increases the risk for adverse cardiovascular and cerebrovascular events, like heart attacks and strokes. If diet and exercise do not lead to improvement, antihypertensive medication may be necessary for many people. A finding reported in a medical journal might identify a previously unknown but rare adverse side effect from one such medication. A reporter might think it their duty to make that adverse side effect known to the public in the spirit of informing people about the risks of their medications. That is an understandable thought. At the same time, however, will the journalist consider that the way they report on the adverse event might make people overestimate a rare risk, generalize the adverse side effect to all antihypertensive medications, or become distrustful of their doctors’ advice to continue taking their medication? Does the journalist think about the potential for their article to have the unintended consequence of motivating some people to stop taking necessary medication, risking serious adverse consequences?

         It is unclear to what extent journalists and editors are aware of the potential their communications have to do harm, although there has been considerable discussion among journalists about the adoption of stronger editorial codes. A Hippocratic Oath for journalists has even been suggested. We believe that a broader set of guidelines is needed around ensuring that what journalists write about and post in the areas of science and health are in the service of the public’s health. Then, we need to work on incentives that will motivate journalists to follow them. Critica is prepared to work with journalists and editors to craft such guidelines and incentives.

Long Covid and the Brain

Inject an agent that stimulates the immune system (usually something called lipopolysaccharide) into a rat and the animal will exhibit a constellation of behavioral symptoms called “sickness behavior.” The symptoms include reduced locomotion, decreased appetite (anorexia), sleepiness, and decreased engagement in usual activities like grooming. In other words, the rat seems to be depressed. Scientists can demonstrate that the immune system activation that causes sickness behavior in rodents also produces physical activation of immune markers in the brain.

         Humans who get infected with various viruses and bacteria can relate: when we are sick we generally have decreased interest in things (called “anhedonia” by psychiatrists and psychologists), decreased energy, sleep disturbances, reduced appetite, and a sad feeling. Is this because stimulation of the immune system by these infectious agents is having a physical effect on our brains or is it a psychological reaction to feeling sick that is not accompanied by any discernible physical brain changes?

         This question, which is very difficult to answer, has become especially relevant during the current coronavirus pandemic. The syndrome of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), better known as Long Covid, has sparked intense interest throughout media and the internet and is the subject of intensive research by basic and clinical scientists throughout the world. Many of the manifestations of Long Covid are neurological and psychological in nature, including headache, “brain fog,” confusion, loss of the senses of taste and smell, depression, and anxiety. This raises the question of how the virus that causes Covid-19 affects the brain. Are the neurological and psychological symptoms of Long Covid related to physical changes in any part of the central nervous system?

Virus Not Detected in Human Brain

         Some viruses are neurotropic, meaning they can infect nervous system tissue directly. Examples are the measles, polio, and rabies viruses. So far, however, scientists have not found evidence that the virus that causes Covid-19 (SARS-CoV-2) is neurotropic in humans, although the virus has been detected in the brains of mice and non-human primates. Autopsy studies have failed to produce any signs of direct infection of neurons or other cells in the brains of people who have died from Covid-19. That means that it is unlikely that ongoing viral brain infection is the cause of Long Covid’s psychological and cognitive symptoms.

         One theory that has been prominently advanced and studied to explain Long Covid brain-related symptoms is the possibility that an ongoing immunological process is affecting the brain. Given the well-established effect in rodents of inflammation elsewhere in the body on both immune function in the brain and on behavior, this is certainly possible. While the evidence for this mounting, it is still far from definitive. 

The Difficulties of Studying the Human Brain

         Studying the human brain is a difficult undertaking because it is encased behind something called the blood-brain barrier, a protective layer of cells and blood vessels that keep many things circulating in the bloodstream from entering the brain and many things in the brain from exiting into the blood. This means that blood tests generally do not reveal much about what is happening in the brain. And unlike other organs of the body, we usually cannot directly sample brain tissue in living people.

         Blood studies have shown that Covid-19 can be associated  with the production of autoantibodies, antibodies that mistakenly recognize tissues of the body as if they were foreign invaders. These autoantibodies have been shown to attack central nervous system tissue in the laboratory and to persist in the blood of people for weeks and even months after recovering from acute Covid-19 infection, suggesting that this could be one mechanism by which abnormal immune system activation affects the brain. It is not known yet, however, whether in fact Covid-19 stimulated autoantibodies do cross the blood-brain barrier in humans and adversely affect the brain.

         Studies using formal neuropsychological testing have shown cognitive abnormalities months after recovery from the acute phase of Covid-19 infection. Brain imaging studies can further tell us many things about brain structure and function. Using the technology of positron emission tomography (PET) scanning, for example, scientists reported decreased metabolism in parts of the brain in patients with severe cognitive impairment in the days following recovery from Covid-19. Six months after recovery from Covid-19, the same investigators found improvement in both cognition and brain metabolism in the study participants, but there were still residual abnormalities in both domains. These are important studies, but they do not provide us with an understanding of the mechanism by which SARS-CoV-2 causes disturbances in brain function.

Positron emission tomography (PET) scanning of the brain can detect abnormalities in regional brain activity (source: Shutterstock).

Animal studies can clarify the effects of the Covid-19 virus on the brain. Studies in a mouse model show that the virus can cause inflammation in the brain without actually entering the central nervous system, with activation of the brain’s immune cells, called microglia. The same pattern of microglia activation has been observed in autopsied human brains. Once again, however, it is unclear to what extent this is a direct result of previous Covid-19 infection or how directly correlated it is with Long Covid symptoms.

Examining the Cerebrospinal Fluid

         That leaves examination of the cerebrospinal fluid (CSF), the fluid that surrounds the brain and runs down alongside the spinal cord. Samples of CSF can be obtained by performing a lumbar puncture, also known as a spinal tap, a standard procedure when brain infections like meningitis are suspected. Although lumbar puncture is less painful than people often anticipate and generally quite safe, it is not something done casually and therefore research studies involving examination of CSF samples often involve relatively small numbers of patients. Furthermore, even though the CSF originates in the brain, what is in it doesn’t always represent exactly what is occurring within the brain tissue itself.

         Studies in which CSF has been sampled from patients with Long Covid are now available. They show elevation of a number of markers of abnormal immune system activation. As noted above, however, these studies involve small numbers of participants and different studies have found different immune systems markers to be activated. Although suggestive, the data do not yet nail down the exact role of immune system activation in Long Covid.

The cerebrospinal fluid (CSF) bathes the brain and spinal cord. It can be sampled via a lumbar puncture, or spinal tap, and can reveal abnormalities in brain chemistry and the presence of abnormal cells or pathogens (source: Shutterstock).

         It is also important to remember that rates of anxiety disorders, depression, and posttraumatic stress disorder have increased during the pandemic. When symptoms of these conditions emerge in people who have recovered from Covid-19 it is difficult to know whether it is the psychosocial burden of living under pandemic conditions that is responsible, the physical effects of ongoing neuroinflammation, or some combination of the two. Because of the stigma surrounding mental illness, it is sometimes difficult to tell patients with Long Covid that one of their problems is depression and that treatment with evidence-based psychotherapy and/or antidepressant medication might be helpful. Here, however, trying to make the distinction between what is “physical” and what is “psychological” may be misleading. There is a long literature on the relationship of depression to immune system abnormalities and overactivation. Hence, it would be unsurprising to find that both psychosocial and immunological factors are involved in Long Covid.

         Evidence is mounting that immune system activation is a factor in the cognitive, emotional, and neurological symptoms associated with Long Covid, but this is far from settled science. As a recent viewpoint article in Science noted “The pathophysiological mechanisms are not well understood, although evidence primarily implicates immune dysfunction, including non-specific neuroinflammation and antineural autoimmune dysregulation.” The search for what causes Long Covid and its brain-related symptoms thus continues.

What Builds Trust in Health Care Institutions?

The psychology of trust should guide our response to health crises.

In January of 2022, at the beginning of a new year that has so far brought renewed surges of COVID-19 cases in the form of an even more contagious variant, the New York Times published an article entitled “For CDC’s Walensky, A Steep Learning Curve on Messaging.” The article reviewed some of the perceived missteps that the Centers for Disease Control and Prevention’s (CDC’s) director Rochelle Walensky has made in regard to communicating ever-changing COVID-19 guidelines to members of the American public. The article pointed to some areas of tension between Dr. Walensky and two other prominent health officials, Dr. Anthony Fauci and Dr. Vivek Murthy, specifically on the decision to reduce isolation time from 10 to 5 days for people with COVID-19 infection (vaccinated or not) without requiring a negative test first. The lack of a united front on issues such as these has certainly contributed to confusion among Americans about what they are supposed to do in various scenarios related to the virus.

Public Trust

While the Times article focuses on “messaging,” and particularly on a failure to provide consistent messaging from a range of government health officials, it’s not entirely clear that “messaging” is what’s at the heart of the problem. While it’s true that there are issues surrounding the way CDC communicates with Americans, the real heart of the problem seems to have more to do with a way in which public officials in this crisis are not understanding and paying enough attention to the issue of public trust.

Postmodern Studio/Shutterstock
Source: Postmodern Studio/Shutterstock

It may be no surprise that evidence suggests that trust in public officials increases the likelihood that people will follow directions in a crisis such as a pandemic. This is why it’s essential that officials understand how trust is built in these situations and how to communicate in a way that will foster this trust. They must stop seeing communication as merely a way to get information to people but also, and maybe more importantly, as a medium to convey trustworthiness. They should therefore constantly be asking themselves: what is the best way for me to craft this message so that it will encourage trust? Because health officials may be too busy or not have the requisite training needed to craft messages in this way, it is important that there be at least one person on staff at relevant health agencies who understands how to communicate well during a crisis.

Consistency and Expectations

Trust is often signaled by consistency and relatively standard and regular expectations. This means that people will expect to hear from health officials at regular intervals and that they expect the communications to build on themselves rather than be full of shocks and reversals. As we have obviously seen with this pandemic, it is impossible for there to be no surprises. We’ve seen changes in recommendations on masks, isolation time, and testing, among other things. What’s important in these situations is for the health official to couch these changes in the context of things that aren’t changing and to acknowledge that the changes themselves might be jarring. Even these small gestures can make the delivery of unexpected news easier. When people feel that they can depend on officials to communicate in a timely fashion and gesture toward and understand how they might feel about unexpected news, they begin to trust these officials.

Some other recommendations for building trust in a health crisis are including a diverse set of experts as communicators, modeling the behavior health officials would like to see in the public, and ensuring that information is always as transparent as possible. Health officials should never allude to something that cannot or will not be shared with the public and should work extra hard to reassure people that when they do not know something, it does not mean they are withholding information. It is also important that health officials communicate with each other and try to reach agreement on scientific issues before they go to the public.

Good communication during a crisis like a pandemic is about more than simple accuracy of information and consistency among health officials. It is fundamentally about what does and does not build trust. Once crisis communications become more focused on this aspect of the public’s relationship with health officials, then we will be able to make more headway in ensuring that more Americans follow guidelines that keep us all safe.