We’re still trying to understand the psychology behind misinformation.

False information about health, particularly about COVID-19, is a growing problem in the U.S. and throughout the world. As researchers and practitioners have tried repeatedly to intervene in this problem, a common question continues to arise: Who is most vulnerable to misinformation? Are there certain psychological or personality profiles that predict someone’s firm belief in misinformation or does it have more to do with the environment and circumstances?

While these are often methodologically difficult questions to answer, we are starting to get some clues. While in the past, there has been a more prominent idea that exposure to misinformation is often sufficient to result in a belief in it, more recently researchers have been questioning whether this is really true. Some of the research thus far suggests that people who are low in certain skills, including cognitive skills, digital literacy, and media literacy, may be most prone to misinformation.

This is by no means to say that people who believe misinformation just lack key knowledge. In fact, these factors around literacy and cognitive skills do not make up most of the reason why people probably believe in misinformation. These factors may only account for a small portion of the issue. It is most likely the case instead that a knowledge deficit is not the reason why misinformation spreads.

There are some other identity characteristics that may make someone more vulnerable to misinformation. Given previous research, it does seem to be the case that while political polarization is a risk factor for believing misinformation, people on the political right are more likely to believe in and spread misinformation than people on the political left. In addition, age and education both seem to be factors, with advanced age associated with a higher likelihood of sharing misinformation, and those with less than a high school degree displaying more vulnerability to believing fake or misleading news.

Source: Snopek/Shutterstock

Research on identity and skills-related factors that predispose certain individuals to believing in and spreading misinformation is helpful, but it still leaves an open question about whether there are certain psychological or personality factors at play here.

In the conspiracy theories field, there has been some useful research tying certain personality traits, such as narcissism, and certain psychological features, such as feelings of loneliness and isolation, to a greater chance of believing in conspiracy theories. But are any of these psychological and personality factors relevant to vulnerability to misinformation as well?

While research on vulnerability to misinformation is mostly still in its infancy, some have suggested that common psychological factors present in childhood may affect adult life in ways that make some people more susceptible to believing misinformation. In general, childhood beliefs tend to be challenged as people get older, but there is a strong emotional inclination to hold onto beliefs from our childhoods that allows us to maintain family peace. As children learn to come up with rationalizations for their firmly-held beliefs and maintain them in the face of challenges, confirmation bias (the tendency to seek out information that agrees with what we already believe) muscles get strengthened all the way into adulthood.

The less challenged a child is about his or her beliefs, the more he or she will excel at coming up with rationalizations that chase away alternative ideas. On the contrary, when children are actively taught skepticism and critical thinking, their confirmation bias “muscle” gets a little weaker. In addition, people with high levels of anxiety are often more prone to confirmation bias, in part because they have a tendency and a strong inclination to block out new information that might be in any way threatening.

Belonging to a social group that believes in a certain type of misinformation might also strengthen the misinformation muscle. Disengaging from this belief can threaten people’s identity and group membership, so we find ways to hold onto it, even when disconfirming evidence comes along.

While our understanding of vulnerability to misinformation is still evolving, there are some factors that we can attend to now. For example, teaching skepticism and critical thinking to young people is always a useful venture. In addition, recognizing that people sharing misinformation might be particularly anxious or trying to defend a deeply-held belief can help build empathy and necessitates a response that is compassionate and understanding. We will never get very far in the fight against misinformation if we don’t truly understand where it is coming from, how it spreads, and who is most susceptible. We have a long way to go in understanding this, but we should take to heart the progress we have made thus far.

What Should We Make of the Colonoscopy Headlines?

No one loves having a colonoscopy, but we have been told that the procedure can dramatically reduce our chances of developing colon (large intestine) and rectal cancer and of dying from colorectal cancer. In fact, the United States Preventive Services Task Force (USPSTF) guidelines recommend a colonoscopy for adults 45 years old and up every 10 years. During the procedure, a long flexible scope is passed up through the large intestine, allowing the trained endoscopist to visualize and biopsy abnormal tissue. Since most cancerous lesions in the small intestine start out as polyps, removing them during colonoscopy can prevent the development of colorectal cancer. Detecting cancer during the colonoscopy permits the initiation of treatment, which can be lifesaving.

         Since colorectal cancer is the second leading cause of cancer death in the U.S. for men and women combined, it would seem to make a lot of sense to follow the guidelines for colonoscopy screening. Hence, it came as quite a shock when media headlines blared out the news that a new study seemed to show that colonoscopy is not as effective in reducing risk for cancer or cancer-related death as expected. The study was published in the New England Journal of Medicine in October and reported the results of research conducted in four European countries, although only results from three countries (Poland, Norway, and Sweden) were reported. In the study, men and women aged 55 to 64 years old were randomized either to be invited to have a colonoscopy or not to be invited to have a colonoscopy. There were 28,220 people in the invited group and 56,365 in the usual-care (no invitation for colonoscopy) group. The participants were then followed for ten years. The researchers found an 18% decrease in risk for colorectal cancer in the invited-for-colonoscopy group and no difference in cancer-related death between groups. That finding contradicts earlier, smaller studies, that found a much larger benefit for colonoscopy and thus the immediate media attention, declaring that the study had failed to find colonoscopy to be of much benefit.

During a colonoscopy, the examiner passes a long, flexible scope through the rectum and large intestine (colon), enabling detection and biopsy of abnormal tissue (image: Shutterstock).

         “Such news coverage has ignited controversy,” wrote Franklin G. Berger, a cancer research scientist, “and created some confusion about the study and its implications, leading people to question whether the results suggest that reevaluation of the utility and need for a colonoscopy is warranted.” Dr. Franklin went on to state, however, that “Many of these news reports mistakenly interpreted the study…Such misinterpretations have grave consequences with regard to efforts aimed at screening and preventing a form of cancer that affects the health and well-being of so many.”

         It is unknown at this point whether the study and its loud media coverage will dissuade people from undergoing colonoscopy. The preparation for a colonoscopy is unpleasant and the procedure has risks like bowel perforation, which, although rare, are serious. It would seem likely that anything that calls the procedure into question might be capable of influencing some people to avoid it. Would they be making a wise decision? After all, the study that ignited these questions was large, carefully done, and published in the world’s most prestigious medical journal. What happens and what should we do when guidelines get called into question by studies that are immediately reported to us in the media?

Taking a Closer Look at the Colonoscopy Study

         If we look a bit more closely at the study, we can see why many experts are pushing back against the conclusion that the findings decrease confidence in the benefits of colonoscopy. Only 42% of the people who were invited to have a colonoscopy actually had one. When the researchers restricted their analyses to just those people who underwent colonoscopy, they found a 31% decrease in cancer risk and a 50% decrease in cancer-related deaths, rates that certainly meet the standard of being clinically significant. A gastroenterologist pointed out two other aspects of the study of note. First, it is more common for skilled gastroenterologists to perform colonoscopy in the U.S. than in other countries and this may increase the rate of detection of abnormal, precancerous tissues. Second, one in four of the colonoscopies in the study were performed without any anesthesia, something rarely done in the U.S. Without anesthesia, colonoscopy can be quite painful, leading the examiner to terminate the procedure earlier without sufficient probing to detect abnormalities.

         Delving into the details of the New England Journal of Medicine report thus leads to different conclusions than may have been apparent from reading the media headlines. It is unlikely, at least for the time being, that the USPSTF or any other medical guideline-producing organization will downgrade their colonoscopy recommendations based on the study. So why did media outlets rush to tell us about the study? Should they have restrained their reporting of it, recognizing that how they presented the findings might lead to adverse health consequences for some people?

Medical Guidelines are Not Infallible

         While we definitely advocate for greater care by journalists and their editors in how they report the results of hot-off-the-press research studies, it is also important to recognize that medical guidelines are far from impervious to the need for change as new research emerges. Last year, a group of physicians wrote in the Annals of Internal Medicine that “Studies of guidelines unfortunately have reported a high proportion of recommendations—including strong recommendations—based on evidence that is low quality and hypothesis generating rather than high quality and hypothesis confirming…” One of the group’s main complaints was “the lack of regular updates” of guidelines. While it is doubtful that the colonoscopy study published last October will justify guideline changes, it certainly is the case that in many other instances guideline recommendations become out of date as new research emerges that indicate changes are needed. For example, the authors of the Annals of Internal Medicine article point to guidelines that once recommended that postmenopausal women receive hormone replacement therapy to reduce the risk of cardiovascular disease and breast cancer even though “large randomized controlled trials subsequently proved precisely the opposite.”

         Right now, a controversy appears to be brewing over new USPSTF guidelines for who should take statin medications that are prescribed to reduce blood levels of LDL (bad) cholesterol. Data are clear that when given to the right patient these medicines can significantly reduce the risk for cardiovascular disease and stroke. The new guidelines were published in the Journal of the American Medical Association last August and recommend that adults aged 40 to 75 years who have 1 or more cardiovascular risk factors and an estimated 10-year cardiovascular disease risk of 10% or greater be prescribed a statin medication. What is the problem with this recommendation? “The USPSTF recommendation excludes many individuals who would otherwise likely benefit from a statin,” concluded a group of physicians who pointed out that the new recommendation is more conservative than a 2018 guideline issued jointly by the American Heart Association, the American College of Cardiology, and other medical societies. In fact, they estimated that “Approximately 16 million fewer adults from 2017 to 2020 would have been eligible for statin therapy” under the USPSTF guideline.

         The reasons for the difference in recommendations here are very complex, but clearly could potentially make an enormous difference in people’s lives. Although this controversy does not seem to have ignited the same degree of media attention as the colonoscopy study, it does seem like something people ought to know about. It is possible that, following the USPSTF guideline, physicians have told millions of people they don’t need statin medication who, according to the alternative 2018 guideline, might benefit from them. Shouldn’t people be aware of this, especially given the fact that health guidelines are hardly infallible?

Statins are a class of medication that reduce the level of low-density lipoprotein (LDL or bad) cholesterol in the blood and decrease the risk of having a heart attack or stroke (image: Shutterstock).

      So here we have a case in which too much media coverage might harm people, while in another case too little media coverage might also cause harm.  

         Challenges to guidelines confuse healthcare providers and their patients and can result in decisions that are not in people’s best interests. We see the need for two solutions. First, we need a better-informed and more careful cadre of journalists and editors who understand how to report on new studies and opinions in balanced, non-sensationalized ways that will really be helpful to their consumers. Second, it is imperative that the medical/scientific community do a better job of communicating to the public the significance of new findings that may necessitate reconsideration of what is in a health guideline.. When differences of opinion emerge among experts so that true consensus is lacking, these need to be reported to the public so that they can seek personalized advice from their own healthcare professionals. In the case of the colonoscopy study, media outlets should have pushed pause before reporting the results, giving time for experts to explain clearly why the new study does not mean we should stop following colonoscopy guidelines, at least for now. In the case of the statin guidelines, reporters should now delve into this potential difference of opinion and if it really represents a lack of expert consensus the public should be informed so that individuals can decide with their own doctors whether a statin is advisable. Better management of health guidelines is therefore required from multiple sources.

But Disparities and Confusion About Science Remain

The Pew Research Center published the findings of its 2021 survey on Americans’ engagement with science last month and the results are somewhat encouraging. “More than half of U.S. adults (56%) say they talk about science news with others at least a few times a month, including about a quarter (24%) who say they talk about science news at least a few times a week.” These rates of science engagement are higher than found in the 2017 survey, when only 44% said they talked about science news with others at least a few times a month. This may in part be due to the Covid-19 pandemic, which brought many aspects of biomedical science to the forefront.

         Other findings from the Pew survey of note include:

·  Three-quarters of Americans have some interest in following news about science.

·  Interest in science was greater than interest in a number of other topics, including business, finance, sports, and entertainment, but less than news about one’s local community.

·  A majority of Americans felt “amazed” by scientific advances.

Many Areas of Concern

These positive trends are welcome, but the report also highlighted some areas of great concern. There were racial disparities in science engagement and interest. When asked about their interest in following news about science, rates of responding “very” or “somewhat” were as follows:

·  Asians: 82%

·  Whites: 78%

·  Hispanics: 69%

·  Blacks: 66%

These racial differences are of course disturbing. Paul L. Morgan, professor of education and demography at Pennsylvania State University noted recently that racial disparities in advanced math and science skills begin as early as kindergarten. In a new study from Morgan’s group, 13% of white and 16% of Asian students showed advanced math and science skills by kindergarten, compared to 4% of Black and Hispanic children. These disparities endure and fewer than 10% of U.S. scientists and engineers are Black or Hispanic.

Of course, advanced skills in science and math and interest in science news are not the same things, but the persistence of decreased scientific engagement among Black and Latinx people in the U.S. should be an area of major concern. Morgan’s findings suggest that these disparities arise early in life and therefore call for interventions to stoke scientific interest among Black and Latinx children at the preschool level.

Other areas of concern included finding that interest in science was correlated with educational level and people with more formal education had greater interest. Interest in science was higher among men (80%) than among women (72%). Democrats expressed more interest in following science news than Republicans.

Science is Confusing

In the Pew survey, a considerable number of people (57%) expressed some level of confusion about science news, “reporting that they feel it is difficult to know what to think due to so much conflicting information.” Americans said they rely on information from scientific experts, but also quite a bit on information from friends and relatives and from online sources. Few reported reliance on information about science from journalists.

The confusion is understandable. We’ve noted on many occasions that things like changing narratives about the value of face masks for preventing transmission of airborne viruses and whether vaccines prevent infection or the serious consequences of infection with the virus that causes Covid-19 are recent examples of things that create confusion about science. But this is hardly a new phenomenon, as we have also pointed out. How often, for example, can people be told that everything they were once told about what foods are best to eat is now wrong without becoming confused about who is making up these rules and what to believe?

Don’t Freak Out About Mistrust

It is also important to distinguish how interested people are in science news with how much they trust science and scientists. We have certainly seen an unprecedented level of mistrust about scientific pronouncements during the pandemic, with guidance issued by health agencies like CDC and FDA often coming under attack both from scientists and politicians. This has had an effect on the public’s trust, but it is important to heed the advice of commenters like John C. Besley, the Eric N. Brandt Professor of Public Relations at Michigan State University, who wrote in October that most Americans have a least a “fair amount” of confidence that scientists act in the public’s best interests. Besley’s article was titled “Most Americans do trust scientists and science-based policy-making—freaking out about the minority who don’t isn’t helpful.”

         Without “freaking out,” however, we do note that in addition to the racial disparities noted above, science engagement is lower among people with less formal education, Republicans, and women. Rather than bemoaning those findings we need to create strategies for reaching out to groups that are less engaged scientifically. It is altogether too easy to cast aspersions at people for not paying attention to what science says and more important to figure what the barriers are to their developing greater interest. As Besley notes, the key to getting people more interested in science is to build trust. “People perceive others as trustworthy if they appear to be caring, honest, and competent,” he wrote. “Unlike politicians, science supporters can’t win by making others look bad…building real relationships with other members of the public will depend on communicating and behaving in ways that demonstrate caring, honesty, and expertise.”

         For instance, how should we approach someone who mistrusts the science of evolution, believing it contradicts a religious doctrine? Often, scientists merely turn away from such people, characterizing their position as “irrational.” That of course is not the way to build “real relationships.” A first step in such a situation is to acknowledge that indeed the notion that species developed over millions of years rather than in single days of a Biblical creation story are incompatible narratives. We have to recognize that religious beliefs are valuable to many people as a way of understanding the world and that characterizing them as irrational or anti-science only drives further wedges. Instead, by affirming that we understand the importance of a world-view that is different from the one science proposes, we have a chance to engage those who are unconvinced by evolutionary biology in conversation. The next step is to locate trusted messengers—in this case firmly religious people who also accept evolution as a true description of the natural world—to be the scientists’ spokespeople. Our goal here is not to dissuade people from their religious beliefs but rather to engender willingness to listen to the case for evolution science.

         Much of this work will have to occur at the level of very early childhood education. As discussed above, we already see racial disparities in some areas of science engagement as early as kindergarten and it is likely that many factors that influence who will be interested in science are in effect by then. The well-known disparity between men and women in science and technology careers probably has similar early origins and has to do in part with the way we do (or don’t) present science to very young children. We need to introduce science as a graspable and inviting discipline beginning at the earliest ages possible and encourage children from minority groups and women to consider science and technology as potential future careers when they are still very young.

         At the same time, we must work harder to develop better ways of communicating how science works to adults. According to the Pew Research Center report, people do not apparently place a lot of trust in journalists for providing accurate science news, but they do seem to trust experts, family, friends, and what they see on the internet and social media. We need to think about each of these in turn and devise strategies to overcome both lack of interest and mistrust. Journalists need better training in how to report science, training that will teach them, for example, to eschew sensationalizing early findings and mistaking animal studies for proof that things work in humans.

One of the key factors here is to help people become more comfortable with scientific uncertainty. It is true that many things about the biology of the coronavirus that causes Covid-19 were uncertain at the beginning of the pandemic; as more knowledge emerged initial recommendations necessarily changed. While there were clear missteps in communication, much of the confusion about Covid-19 stemmed from the fundamental way that science works. Scientists must become more adept at alerting people to what they don’t yet know and the public more tolerant of uncertainty.

         While it is encouraging that most Americans seem to want to know what is going on in the world of science, are amazed by scientific discoveries, and trust scientists to give them accurate information, there are many troubling aspects to this most recent Pew Research Center report. Discrepancies in scientific engagement stubbornly remain among Black and Latinx people, women, and Republicans. Too many people say they are confused by what science and scientists are telling them. While we agree with John Besley that “freaking out” is not the best approach to tackling these issues, we do think that concerted efforts to address them are essential.

A Study Finds a “Strong” Association

In a study published last month in the journal JAMA Psychiatry, investigators from the Harvard T.H. Chang School of Public Health and Harvard Medical School reported that among individuals followed up for more than a year starting in April 2020 the presence of several types of psychological distress at baseline and before COVID-19 infection was “strongly associated” with subsequent development of Long Covid.  What these researchers are reporting on is a strong association between preinfection psychological distress and symptoms of Long Covid, the illness that occurs in about 30% of people after they have recovered from COVID-19. Other data already suggest that patients who have survived COVID-19 are at increased risk to develop psychiatric illnesses like depression and anxiety disorders.

         We all know and agree that association is not causality and therefore the authors of this study were appropriately careful not to say that psychological distress is a cause of Long Covid. Unpacking the study, however, makes it clear that this could be one possibility in some cases. The researchers used data from three large ongoing epidemiological surveys and included 54,960 participants in the study. They assessed these study participants for psychological distress before they reported being infected with SARS-CoV-2, the virus that causes COVID-19. They used a careful statistical analysis that controlled for many potentially confounding variables to find a strong association between depression, anxiety, worry, loneliness, and stress and subsequent Long Covid.

A Caveat from the Authors

         Knowing that this finding is bound to spark controversy, the authors made a curious statement in the discussion section of their paper: “Our results should not be misinterpreted as supporting a hypothesis that post-COVID-19 conditions are psychosomatic.” They list several reasons for that assertion including:

·  More than 40% of the participants who developed Long Covid did not report psychological distress prior to developing COVID-19.

·  Symptoms of Long Covid “differ substantially” from symptoms of mental illness.

·  More than half of the patients reported relapses after physical exercise, whereas physical exercise has been shown to be protective against relapses of many forms of psychiatric illness. 

They go on to explain potential biological links between psychological distress and Long Covid involving the immune system and inflammation, which we will return to in a bit. Somehow, the authors seem to want to reassure their readers that they do not regard Long Covid as in any way a “mental illness” or merely “psychosomatic.” Rather, they want us to be clear, there is biology underlying the association between psychological distress and Long Covid and therefore Long Covid must be a “real” illness.

What the authors are obviously responding to here is the long-standing debate about the causes of conditions that sociologists have called “contested illnesses,” a list that includes chronic Lyme disease, fibromyalgia, and chronic fatigue syndrome/myalgic encephalomyelitis. These are illnesses for which there is often disagreement between traditional medical experts and patients about their “nature, causes, and treatments.”  The authors of the JAMA Psychiatry paper noted that “Prior studies have further suggested that distress is associated with long-term symptoms after Lyme infection and in functional syndromes, eg. chronic fatigue syndrome and fibromyalgia, that have symptoms similar to those of post-COVID-19 conditions, such as fatigue, headache, and muscle pain. Yet any suggestion that these “functional” syndromes are linked in any way to psychological factors brings out an immediate outcry from patient advocacy groups, who say that making such a link is akin to asserting that these illnesses are “all in the head” and therefore not real.

Advocates for people with conditions like Long Covid, chronic Lyme disease, and chronic fatigue syndrome are absolutely right to insist that the very real suffering these conditions impose must be fully recognized by the medical profession and that patients who have them should be taken seriously and offered appropriate medical tests and interventions. But it is important to remember that the same is also the case for people suffering from depression, anxiety disorders, and other sources of significant psychological distress.  Trying to negate the possibility that conditions associated with psychological distress might be one cause of Long Covid has the effect of minimizing the reality of psychiatric illness.

Positing a Biological Basis

   The authors of the JAMA Psychiatry paper do not want anyone to think that Long Covid is a “psychosomatic” disorder, a term that is usually taken to mean a psychological condition in which the presence of physical symptoms are unexplained by a known medical illness. To counteract this possible misunderstanding of their findings, they stated that “Inflammation and immune dysregulation may link psychological distress with post-COVID-19 conditions” and mention evidence that stress, as well as depression and other psychiatric illnesses, may activate a biological system called the hypothalamic-pituitary-adrenal axis. This is a system that links a brain region, the hypothalamus, to the pituitary gland that sits at the base of the brain, to the adrenal glands, which are located on top of each kidney. The result of activation of this axis is an increase in several hormones linked to stress, including the adrenal hormone cortisol. Interestingly, cortisol suppresses immune function and has recently been shown to be decreased in patients with Long Covid. Hence, whether there really is a link among hypothalamic-pituitary-adrenal axis function, psychological distress, and Long Covid remains very much an open question.

   Somehow, there is the idea here that if we can find a “medical” or “biological” reason for the association between psychological distress and Long Covid (or any other illness where psychological distress is relevant), then we have removed the association from the realm of mental illness. The fact is, however, that we don’t actually know for sure what is the “biological” basis of either psychiatric conditions or of Long Covid. We have lots of data addressing this issue and it is likely that some answers, at least in the case of Long Covid, will emerge soon. We do know that both are accompanied by significant suffering and disability. We also know that both require careful attention from healthcare professionals. If it turns out that having a history of depression, anxiety disorder, or some other form of psychological distress increases the risk for Long Covid, we should be cautious in offering unproven hypotheses to explain that association. Rather, the new study tells us that psychiatrists, psychologists, and other behavioral healthcare professionals will undoubtedly play an important role in understanding and treating Long Covid.

An August report from the U.S. National Center for Health Statistics, a branch of the Centers for Disease Control and Prevention (CDC),  paints a glaringly disturbing picture of life expectancy for the American population.  For the years 2020 and 2021 the U.S. experienced its sharpest decline in life expectancy in 100 years, falling especially heavily on American Indians and Alaskan Natives. In 2021, the average American could expect to live 76.1 years, a decline from 2020 of 0.9 years. Worse, there was a decline of 1.9 years in that period for American Indians and Alaskan Natives to levels not seen since 1944.

         Deaths from Covid-19 account for most of that decline, but a substantial amount also came from unintentional accidents, mostly overdoses. These data are dismaying on their own, but behind them are other disturbing facts. A New York Times article published just after the release of the CDC mortality report extensively quoted Dr. Steven Woolf, director emeritus of the Center on Society and Health at Virginia Commonwealth University, who noted that the decline in life expectancy in the U.S. was more severe and is continuing for longer than in other high-income countries. Quoting from the article:

“None of them experienced a continuing fall in life expectancy like the U.S. did, and a good number of them saw life expectancy start inching back to normal,” Dr. Woolf said.

Those countries had more successful vaccination campaigns and populations that were more willing to take behavioral measures to prevent infections, such as wearing masks, he said, adding: “The U.S. is clearly an outlier.”

         It thus appears that the portion of the steep decline in life expectancy that is attributable to Covid-19 is worse in the U.S. than in other high-income countries and this can be ascribed to our general lack of preparedness and to the political divisiveness that made following public health recommendations a matter of partisan ideology instead of evidence-based practice. Many Americans sadly have fallen for misinformation about the pandemic and believe that face masks don’t reduce the risk of transmitting and acquiring disease (they do) and that vaccinations are unsafe and ineffective (they are in fact both safe and effective). The price Americans are paying for listening to misinformed voices is obviously profound.

         A second sad truth that can be gleaned from the CDC life expectancy data concerns the fate of American Indians and Native Alaskans. Again quoting the New York Times story:

Average life expectancy in these populations is now “lower than that of every country in the Americas except Haiti, which is astounding,” said Noreen Goldman, professor of demography and public affairs at the Princeton School of Public and International Affairs.

         While it is true that the bulk of the reason for the decline in life expectancy among American Indians and Native Alaskans is due to the Covid-19 pandemic, that doesn’t explain why these communities suffered a much greater effect than other groups. Experts explain that the reason for this is that American Indians and Native Alaskans have higher rates of underlying conditions like diabetes and obesity, which make Covid-19 deadlier. Once again from the New York Times story:

Longstanding health problems — rooted in poverty, discrimination and poor access to health care — left Native Americans and Alaska Natives particularly vulnerable to the virus, said Dr. Ann Bullock, former director of diabetes treatment and prevention at the federal Indian Health Service agency and a member of the Minnesota Chippewa Tribe.

As of 2019, 5.7 million people were classified as American Indian or Alaskan Native, groups of people who experience some of the worst health outcomes in the U.S. As Dr. Bullock explains in the quote above, this is largely due to structural racism and adverse social determinant of health, like crowded living conditions and poor access to healthcare.

In 2019, an American could expect to live to be 79 on average. In 2021 that average lifespan was down to 76. Black Americans had a life expectancy of only 71 in 2021; American Indians and Native Alaskans even lower at 65. While other countries’ mortality statistics have rebounded from Covid-19, the U.S. continues to have high death rates, due in part to vaccine hesitancy. We also do worse than other high-income countries in surviving heart disease, chronic liver disease, and cirrhosis and we have experienced an outbreak of drug overdoses and suicides, the latter fueled in part by our refusal to control private gun ownership.

         The health of Americans compared to citizens of comparable countries is not good. Our fragmented, profit-driven healthcare system makes accessing healthcare difficult for millions, even those who have health insurance. We place the highest burdens on minority groups, offering them the worst access to healthcare and depriving them of many things that are associated with improved health outcomes. Our Critica readers will agree that this situation is morally wrong and intolerable. We can hope that the Covid-19 pandemic taught us that we need to be better prepared for the next infectious disease outbreak, but even accomplishing that will not fix the fundamental reasons that groups like the American Indians and Alaskan Natives living among us have the most dismal healthcare outcomes and the highest mortality rates. Perhaps the fact that we are dying younger in recent years will persuade us that it is time to make major structural changes in our healthcare system and the way we treat marginalized communities.

Monkeypox is hardly a new viral infection. It has been endemic to countries in Central and Western Africa for decades, even before 1970 when it was first identified in the Democratic Republic of the Congo. What is new is an outbreak in 82 newly affected countries globally that began several months ago and is challenging our ability to effectively communicate about health and science to the public.

         In the Monkeypox outbreak in newly affected countries, like the U.S., about 95% of the reported cases have occurred among men who have sex with men (MSM). Epidemiological trends confirm that most of these cases often occurred in MSM with multiple partners. It might seem logical, then, that public health communications should be directed mainly to the community most affected by monkeypox.

         However, such a strategy raises at least two problems for public health communicators. First, we know from the HIV epidemic how easy it is to stigmatize sexual minority communities by targeting only them with health information. We don’t want to make the mistake of facilitating anyone falsely labeling monkeypox a “gay disease” as happened with HIV. The pain and suffering this caused members of the MSM community is still incalculable.

         Second, monkeypox is biologically capable of infecting anyone who comes in close physical contact with an infected person or animal, regardless of their sexual orientation. In previously affected African countries where monkeypox has caused outbreaks for years, more common modes of exposure to the virus and possibly transmission are either from animal bites—the monkeypox virus is found in a variety of animals including rodents—or from preparing animal products intended for human consumption . This is not a “gay disease,” but rather an infectious outbreak that is currently affecting the MSM communities and social networks the hardest.

Reluctant Public Health Messengers

         Because of understandable skittishness around how best to walk these fine lines, public health communicators began by seemingly not trying too hard to communicate about monkeypox at all. It took time, for example, for the World Health Organization (WHO) to advise the MSM community to limit sexual contacts, especially anonymous ones, and consider keeping covered during intimate encounters. The U.S. Centers for Disease Control and Prevention (CDC) took even longer to issue that guidance, not offering direct advice to the MSM community until August 5, a week after the WHO.  Furthermore, Fenit Nirappil commented in the Washington Post that “The CDC did not widely promote its new guidance after rereleasing it online…A tweet and accompanying video linking to the changes did not mention the new recommendations to reduce exposure, including limiting partners.”

Predictably, misinformation and disinformation have flourished on the internet and social media platforms. Our colleagues at the University of Pennsylvania’s Annenberg Public Policy Center found in a survey that there is widespread misunderstanding about monkeypox among the U.S. respondents. For example, two-thirds of people were either not sure or did not believe there is a vaccine for monkeypox (there are two, see below) and 12% believe it is probably or definitely true that the monkeypox virus was bioengineered in a lab. In its most egregious form, a Twitter post identified by the Annenberg team alleged that parents should keep their children away from gay caretakers for fear of spreading monkeypox to them, a totally baseless claim. That tweet has since been taken down.

         In a critique of the CDC’s handling of the monkeypox outbreak last month in the New York Times, columnist Ross Douthat wrote:

And then along with these failures came an absurd ideological spectacle, in which health officials agonized about how to state the obvious — that monkeypox at present is primarily a threat to men who have sex with men — and whether to do anything to publicly discourage certain Dionysian festivities associated with Pride Month. As the suffer-no-fools writer Josh Barro has exhaustively chronicled, public-health communication around monkeypox has been an orgy of euphemism and wokespeak, misleading and baffling if you don’t understand what isn’t being said.

         Douthat’s critique here may be excessively harsh; we empathize with the dilemma CDC faced under these circumstances. But he is right that communication about monkeypox specifically to the MSM community and to the broader public was slow, confusing, and generally inadequate. CDC is an outstanding agency for the detection of infectious agents, but  is repeatedly falling short in communicating appropriate guidance to the public.

A Bit About the Monkeypox Virus

         Monkeypox is caused by a virus in the orthopoxvirus genus and belongs to the same group as its more lethal close relative, variola, the causal agent of smallpox. There are two main strains of the virus, now called Clade I and Clade II. Clade II, formerly known as the West African clade, has been detected in cases from the ongoing outbreak in newly affected countries. It  causes less severe disease (2-3% mortality) than Clade I, which is endemic to Central Africa’s Congo Basin, and has a mortality rate of as high as 10%.

People who get monkeypox experience a variety of flu-like symptoms like swollen lymph glands, fever, and muscle aches, but the hallmark of monkeypox is the large, crusted, lesions that form on the skin where the virus concentrates. In the current outbreak in newly affected countries, atypical presentations with a predominance of painful in oral, genital, and anal lesions have been noted, likely a reflection of transmission through close intimate contacts facilitated by sex playing a key role in new infections in the current outbreak

   

The hallmark of monkeypox is typical pox-like skin lesions in which the virus concentrates. Close and prolonged contact with these lesions is the main mode of transmitting the virus from one person to another (image: Shutterstock).

The most common mode of transmission is clearly via close and extended physical contact with active pox lesions. Other modes of transmission like prolonged contact with contaminated objects such as bedding or clothing and droplets/aerosol are possible but not considered to be the primary modes of transmission. Although monkeypox virus has been isolated from seminal fluid, it is not officially described as a “sexually-transmitted infection” because actual transmission by exchange of semen has not been definitively documented. Similarly, although monkeypox virus can be found in large respiratory droplets like those that originate from a cough or sneeze, it is not clear how much if any transmissions occur by inhalation of infectious droplets. Household transmission appears uncommon, and the risk of transmission by aerosolized respiratory droplets in a manner similar to the Covid-19 virus is considered very low.  Hence, it is not likely that one can become infected with monkeypox simply by being in the same room as someone who has it; close and sustained contact with the actual lesions appears to be by far the most common mode of transmission.

Vaccines and Medication Are Available

         Prevention of monkeypox begins of course with limiting physical contact with people already infected. Two vaccines are authorized for monkeypox prevention in the U.S. One is a smallpox vaccine called ACAM2000, which contains a less virulent orthopoxvirus (vaccinia virus) that is capable of replication. It can cause adverse side effects in people who receive it, especially in immunocompromised people for which it is contraindicated , including people with HIV who are not on antiretroviral  treatment . There is also the Jynneos vaccine, which contains a modified vaccinia virus that does not replicate. It is manufactured in Denmark, has fewer adverse side effects, and can be used in immunocompromised individuals but is in short supply. To expand the supply, the CDC recently recommended giving it in lower doses and using a different injection method than originally authorized. Finally, the antiviral drug Typoxx, also in short supply, can be used to treat monkeypox.

Equitable Treatment is Lacking

         We have stressed that monkeypox is not a new illness to highlight that once again a virus has only gotten attention only when it affects high-income countries. As Critica Chief Scientific Advisor B.K. Titanji, an infectious disease specialist at Emory University, recently Tweeted: “Mixed emotions again vaccinating and protecting folks and their communities amidst a global outbreak…Knowing fully well it could be years before communities in Africa, S. America, and Asia are able to do the same. We need EQUITY in Global Health.”

         Even in the U.S. there are clear inequities in infection rates and treatment, with Black MSM in certain southern states having higher rates than white men and having more difficulty accessing preventative services and treatment.

         So there are two imperatives for controlling monkeypox. One is to pay immediate attention to the disease in Africa by getting vaccines and other preventative and treatment measures to people who have been dealing with monkeypox for decades.  Similarly, we need to get vaccines and treatments to people at high-risk for monkeypox in non-endemic countries, especially MSM from minority communities. Equitable attention and access to treatment globally and within the U.S. are clear moral and medical imperatives.        

The other imperative is to learn from our science communication mistakes once again, as we have been forced to do with the Covid-19 pandemic. It should not be so difficult for public health agencies to figure out early messaging that can deal with difficult situations, like that presented by monkeypox. We need to ensure that the community most affected by monkeypox gets reliable information, and that means communicating directly with the MSM community with facts and options. Guidance should not be hedged but must be explicit in explaining what kinds of contacts are most likely to spread disease and what preventative measures most likely to offer protection. At the same time, it must be made clear to the general population that monkeypox is not a “gay disease,” but rather one that can affect anyone. The aim here is not to generate public hysteria; it is unlikely that monkeypox will spread through the U.S. population the way Covid-19 has. Rather, it is to make clear that everyone must take monkeypox seriously and care about those most likely to be affected. More than anything else, it is a plea to public health agencies like CDC to develop better policies and practices around public communication, making them more rapid, relevant to specific communities, and effective in shaping health-promoting behaviors.

A Paper About the “Serotonin Hypothesis” Stokes Controversy

Even though depression is one of the most common conditions in the world and we know many of the things that increase the chances of getting it (e.g., early life stress, being female, serious medical illness, grief and loss), scientists still do not understand precisely what causes it. When it comes to treating depression, we have many effective interventions, including a range of evidence-based psychotherapies and antidepressant medications, but once again knowledge about exactly how any of these work to alleviate depression is lacking.

         A recent paper and subsequent commentaries that seemed to debunk one theory about how antidepressant medications work received a lot of attention and led its authors to decry the use of these medications. Written by European authors, the paper is a systematic “umbrella” review of the “serotonin theory of depression.” The authors conclude that there is little evidence supporting the serotonin hypothesis and therefore that a whole class of antidepressant drugs, called selective serotonin reuptake inhibitors (SSRIs), may not actually work. In a bold statement the authors of the review paper concluded “Our study shows that [the serotonin theory] is not supported by scientific evidence. It also calls into question the basis for the use of antidepressants.” This is a classic example of authors of a paper making conclusions that go well beyond their data.

The Serotonin Hypothesis of Depression

         What is the serotonin hypothesis of depression? Many antidepressant drugs have the property of quickly increasing the amount of a neurotransmitter in the brain called serotonin or 5-HT. Serotonin then binds to specific receptors in the brain, one type of which is also the site where the SSRIs and other types of antidepressants bind. This raised the question decades ago in scientists’ minds of whether low brain levels of serotonin or some decreased ability to utilize serotonin might be a cause of depression. As the paper by Joanna Moncrieff of University College, London and colleagues published in the journal Molecular Psychiatry showed, efforts to measure serotonin in blood, urine, and cerebrospinal fluid of patients with depression have failed to show any deficits, but this is not surprising because the levels of neurotransmitters in the brain are poorly reflected by levels in these peripheral bodily fluids. Moncrieff and colleagues also reviewed studies of various receptors and genes connected to the serotonin system and once again did not find any evidence supporting the simplistic serotonin hypothesis. In the Molecular Psychiatry paper, they concluded “Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentration or activity.”

         So far, Moncrieff and co-authors make a reasonable case that low levels or activity of serotonin is probably not the cause of depression, nor do SSRIs and other antidepressants work simply by increasing the amount of serotonin in the brain. Yet, this conclusion is hardly news: very few scientists actually subscribe to such a simplistic version of the serotonin theory at this point. From the very beginning, even before SSRI antidepressants were first approved in 1987, scientists noted that the drugs increase serotonin levels after just a few doses, but it takes weeks of administering them before depression symptoms actually begin to respond. Obviously, something other than simply low levels of serotonin must be involved. All Moncrieff et. al. did was to accumulate years of research about this in one paper, a useful service perhaps but not a novel observation. Where things get controversial is in the conclusions they draw from their review.

Overreaching from Data to Conclusions

         “There is no other accepted pharmacological mechanism for how antidepressants might affect depression,” Moncrieff and co-author Mark A. Horowitz write about in a paper about their research in The Conversation. “If antidepressants exert their effect as placebos, or by numbing emotions, then it is not clear that they do more good than harm…We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe.”

         Does the fact that a theory about the mechanism of action of a medication turns out to be unsupported mean that the medication is ineffective or unsafe? Obviously, this is not automatically the case and the conclusions that Moncrieff and Horowitz reached are themselves unsupported by any data they provide. The FDA approves antidepressants if there is sufficient evidence they are superior to placebo in clinical trials. All the available antidepressants in the U.S. have met that test. That doesn’t mean of course that antidepressants work for every patient with depression, that they are sufficient to completely eliminate depression even in patients for whom they have some benefit, or even that they are the best treatment for depression. Many patients with depression will do better receiving psychotherapy than medication; some need a combination of the two interventions; and some will do best with antidepressants alone. Nor does the fact that the antiquated serotonin hypothesis is not likely to explain how antidepressants work have any relevance to the issue of their safety. Moncrieff and Horowitz seem to believe that antidepressants merely “numb” emotions and are no better than sugar pills, but nothing in their review paper substantiates that claim.

         In another commentary, Srijan Sen, head of the University of Michigan’s Depression Center, asks “Do we need to understand exactly how a drug or a non-drug treatment works in order to use it? No — if that were true we would have no treatments for depression, whether it’s drugs, like SSRIs, psychotherapies like cognitive therapy, or lifestyle changes like more consistent sleep patterns.” And Sen notes that “by coincidence” another study was published at around the same time as the Moncrieff paper that does show evidence for involvement of the serotonin system as a cause of depression. That paper, published in the journal Translational Psychiatry, is quite technical and did not garner media attention. Yet it suggests that a combination of adverse life experiences and mutations in a serotonin receptor gene does seem to be involved in why some people become depressed.

         Although Moncrieff and co-authors are careful to caution people on antidepressants not to stop them without discussing with their prescribers, their warnings seem half-hearted. Implicit in their comments is the message that if what they misunderstand to be a prominent hypothesis about how antidepressants work—correcting low levels of serotonin in the brain—doesn’t hold up then maybe the use of antidepressant medication is called into question. Media seemed intrigued by that message, which is clearly not a logical conclusion. What they have simply provided us with is another reminder that the human brain is incredibly complex and difficult to study and that in many instances treatments for human diseases, especially when they involve the brain, work without our knowing why they work. The easiest thing to do here is to call for more research, which of course we do and will happen. More to the immediate point, however, is to urge scientists to be cautious in leaping to conclusions and the media to put things in the correct perspective.

A 24-year-old man makes a visit to his primary care doctor because of a severe headache that has been bothering him for 24-hours. The doctor takes a history and learns that the man has otherwise been in good health, exercises regularly, does not smoke or use drugs, and has no significant family history relevant to headaches. A physical examination is also normal including a normal blood pressure. The doctor tells the patient that it is unlikely that there is anything seriously wrong with him, inquires whether he has been under an unusual amount of stress lately, and advises him to take an over-the-counter pain medication (acetaminophen) and to call if the headache does not subside over the next 24 hours.

         This is a typical scenario for a primary care visit and the overwhelming odds are that this young man indeed has nothing seriously wrong with him, is suffering from a tension headache because of stress, and will feel much better after a few doses of the painkiller and a few hours. Yet in many cases patients do not feel satisfied with an encounter like this. In this instance, our patient feels that his doctor did not appreciate the severity of his symptoms or consider all the possible underlying causes for them. So he goes home and searches the internet for causes of headaches. He reads that a type of brain tumor called glioblastoma multiforme (GBM) is the most common form of brain cancer, that it is virtually incurable, and that severe headache is one of the early symptoms. Our patient wants a magnetic resonance imaging (MRI) scan of his head without delay. He leaves a message with the doctor’s office making that request and becomes very frustrated when a day later he has not heard back. Fortunately, at that point his headache is better, so he now resolves to find a neurologist who will order the MRI scan he thinks he needs.

Article Identifies Medical Gaslighting

         A recent article in the New York Times by Christine Caron highlights instances in which people do not feel their doctors are listening to them. “The experience of having one’s concerns dismissed by a medical provider, often referred to as medical gaslighting, can happen to anyone,” Caron wrote in the article published last July. Caron writes about people whose symptoms were dismissed by medical professionals, only to turn out to have serious illnesses. “A recent New York Times article on the topic,” she explains, “received more than 2,800 comments: Some recounted misdiagnoses that nearly cost them their lives or that delayed treatment, leading to unnecessary suffering. Patients with long Covid wrote about how they felt ignored by the doctors they turned to for help.” She also notes that the problem of “medical gaslighting” appears to be worse for “women, people of color, geriatric patients and L.G.B.T.Q. people.”

         To read the article by Caron, one might get the impression that there is a widespread breakdown of communication between patients and their doctors, and that dismissal of symptoms is a common phenomenon. Furthermore, the article implies that doctors routinely miss real disease because they don’t take what patients tell them seriously.

         Caron cites a study “using data from 2006 and 2007 [that] estimated that approximately 12 million adults were misdiagnosed in the United States every year and about half of those errors could be harmful.” When we looked at that study, however, we also noted that the rate of those errors, which involved colon and lung cancer cases that were not initially diagnosed, was 5.08%. In other words, no misdiagnosis was detected in almost 95% of the cases the investigators examined. While finding misdiagnoses in 1 out of 20 patients is very far from trivial, it does put in perspective the sense from the article that misdiagnoses are common. We believe that a more common problem is the breakdown of communication between patients and their healthcare providers. Let’s look first at what was probably on the mind of the doctor who saw the patient in our fictional example.

Using Pretest Probability to Make Medical Decisions

         When a physician or other healthcare provider is faced with a set of symptoms reported by a patient, one of the very important things they consider is the “pretest probability” of different potential diagnoses. In the case of our young man with a headache, for example, we know that the rate of GBM is 3.19 per 100,000 people and that the median age of diagnosis is 64. Thus, the chances that a 24-year-old man with a normal neurological examination has a GBM are vanishingly small. Much more likely are other types of headaches, like tension and migraine headaches. MRI scans are expensive and unhelpful in detecting the causes of most headaches and health insurers balk at paying for unnecessary medical procedures. Finally, waiting a few days to see if the headache goes away would have minimal consequences if our patient really did have a brain tumor. In this case, the doctor’s advice on a plan of action was entirely reasonable.

         Yet it did not seem so to our patient. Indeed, a survey published last year found that “Three in 4 Americans leave the doctor confused and dissatisfied for reasons that include disappointment in the level of Q & A they have with their doctor, confusion about their health, and a need to do more research…” Nearly half of people research their doctors’ suggestions after a visit. A breakdown in communication between healthcare providers and patients seems to be at the root of this issue.

         And a key cause of this breakdown is probably the fact that primary care providers, and many other healthcare professionals, find themselves overloaded by the demands made on them, particularly by the need to record every aspect of a patient encounter in the electronic health record (EHR). A study published last July in the Journal of General Internal Medicine showed that primary care doctors would need 26.7 hours a day to complete all the work that is asked of them. This problem spills over into many aspects of healthcare: in a recent visit to an emergency department at a major urban teaching hospital, a member of the Critica team witnessed scores of doctors and nurses huddled in front of computer screens trying to complete EHR requirements while patients waited for hours to be seen. While anecdotal evidence like this must be taken lightly, it is consistent with many reports we have heard and with the Journal of General Internal Medicine study showing that doctors simply don’t have enough time to spend providing direct care to patients. It is hardly surprising, then, that some people feel their doctors aren’t listening to them or sufficiently addressing their questions and concerns. Many are turning to the internet for information, where they may or may not obtain accurate information.

Solutions for Medical Gaslighting

         In her New York Times article Caron lists six signs of medical gaslighting, most of which center on poor communication style, including “You feel that your provider is being rude, condescending or belittling.” One of the six is “Your provider will not order key imaging or lab work to rule out or confirm a diagnosis,” but as we have pointed out, that one is not always a sign of gaslighting but is more likely to be a question of a physician applying pretest probability logic to make a decision that expensive or invasive tests are unlikely to contribute information that would influence a course of treatment.

         Caron also offers suggestions for how patients can advocate for themselves and steps to take if a person still feels ignored, including switching providers and joining a support group. The latter is also more complicated that she suggests, however, because support groups may or may not be sources of accurate medical information. Some can help patients through difficult situations and offer valuable advice, but others create an adversarial relationship between doctors and patients and promote interventions that are not evidence-based.

         Solutions to the medical gaslighting problem should not rest solely on patients’ shoulders of course. While Caron’s suggestions are mainly good ones, they do not go far enough. Two things need to happen on the healthcare providers’ side of the issue. First, it is now abundantly clear that the age of the EHR and other changes in medicine have put ridiculous demands on healthcare providers that force them away from their most important task, interacting directly with patients. This needs urgent attention and reform. While the EHR offers a multitude of advantages over old-fashioned handwritten charting, it now places an impossible workload on doctors and nurses and needs to be fixed. Second, much more attention needs to be paid to training doctors and other healthcare workers how to communicate with patients. While this may seem obvious, it is not necessarily a routine part of medical training. Caron paints a bleak picture of doctors who don’t answer questions, condescend to patients, and ascribe symptoms to mental health issues without offering any actual mental health help. Relieving some of the administrative burden on doctors should make it easier for them to spend more quality time with patients but teaching doctors how to communicate effectively is also needed.

         It is unclear how common medical gaslighting is and it is critically important that we not encourage unnecessary medical testing and procedures. Still, Caron does an important service in identifying a growing rift between doctors and their patients. We believe that a large portion of the cause of that rift rests in unreasonable demands on doctors’ time and lack of training in how to communicate with patients. Both are remediable issues that require our attention.

Switching Focus on Treatments for Alzheimer’s disease

There is an old joke in science about a police officer walking his beat one dark and gloomy night when he comes upon a man furiously searching for something beneath a streetlight. “What are you looking for?” the officer asks the man. “I lost my car keys,” the man replies. “Is this the area where you lost them?” the officer queries. “No, but it is the only place on the whole block where there is any light,” is the man’s answer.

         Those keys could, of course, be anywhere, and the decision to limit the search to the place where the streetlight shines strikes us as clearly irrational and a bit funny. Not so funny, however, when logic like this seems to inhibit progress in learning the causes of and treatments for a life-limiting disease. This, unfortunately, appears to be what has happened in the case of Alzheimer’s disease research. We wrote a year ago about the then recently U.S. Food and Drug Administration (FDA)-approved drug Aduhelm, which is essentially an antibody directed against an abnormal protein called beta-amyloid that is found in plaques on postmortem examination of brains from people who had Alzheimer’s dementia during their lifetimes.

         It has always been unclear if Aduhelm actually works to prevent or reverse memory loss in patients with Alzheimer’s disease. There has been a strong outcry from the scientific community protesting the FDA approval of the drug because the evidence that it does more good than harm for people with Alzheimer’s disease is thin. Because there are currently no effective treatments for Alzheimer’s disease, it might be understandable that an agency would want to err on the side of approval. The FDA, however, is supposed to make its decisions based on solid scientific evidence for efficacy and lack of harm, not out of sentiment. Why, in the face of very little solid evidence for efficacy, was this anti-amyloid drug approved? Why do scientists and regulators persist in pursuing the anti-amyloid strategy at all?

Amyloid Plaques Seem a Likely Culprit

Ever since Alois Alzheimer first described changes in the brains of people that had the disease that bears his name, scientists have focused on the idea that the buildup of amyloid plaques in the brain is the cause of the severe memory loss experienced by patients with Alzheimer’s disease and reckoned that eliminating them would somehow improve cognitive function and slow the inevitable progression of the disease to death. Directing antibodies against the proteins that are the main ingredients of the amyloid plaques seems like a logical idea. In a recent STAT piece, Howard M. Fillit, a neuroscientist and geriatrician at the Icahn School of Medicine at Mount Sinai and co-founder and chief scientific officer of the Alzheimer’s Drug Discovery Foundation, explained that “When Alzheimer’s disease was believed to be caused solely by the accumulation of amyloid protein in the brain, pinning all hopes on an amyloid-targeting drug like Aduhelm…made sense.”

         Indeed, enormous amounts of research funding and effort have been expended on understanding the biology of the amyloid plaque and trying to figure out how to eliminate it from the brain. Amyloid plaques collect between neurons in the brains of people with Alzheimer’s disease and there is no question that they are toxic to brain function. On autopsy, amyloid plaques are easy to see under a light microscope and extracting the proteins that make them also relatively straightforward. This makes them an ideal research target. It is, after all, where the light seems to be shining.

Anti-amyloid Drugs Persistently Fail

But there have always been signals that the buildup of amyloid plaques is probably not the only cause of Alzheimer’s, if it is even one of the causes at all. For example, Alzheimer’s disease generally begins in a part of the brain called the entorhinal cortex, a brain region critical for short-term memory and navigation through physical space. Yet, plaques are “not primarily observed in the entorhinal cortex.”  One attempt after another to prevent or treat cognitive function loss in Alzheimer’s disease by targeting amyloid plaques has failed. One thought that occurred to scientists after the first few failures was that perhaps by the time a patient has advanced disease it is too late to induce improvements by trying to reduce the amyloid plaque burden. So, researchers decided to pursue clinical trials with anti-amyloid drugs involving people with the earliest signs of Alzheimer’s disease.

         This strategy, unfortunately, also seems like a dead end. In June, the Roche drug company announced the failure of its experimental drug crenezumab in a much anticipated study. The study involved people with a relatively rare genetic mutation that causes early-onset Alzheimer’s disease. Crenezumab is another antibody-based medication that targets amyloid plaque protein, and in this trial it was compared to placebo in study participants with the mutation who did not yet have signs of the disease. Yet crenezumab did no better than placebo in preventing onset of or slowing cognitive decline, indicating that even addressing Alzheimer’s disease in its earliest stages with anti-amyloid drugs does not seem to work.

         The perseverance of interest in amyloid plaques as the main treatment target for Alzheimer’s disease, while understandable, represents one not uncommon problem with research, perhaps especially relevant when it involves diseases of the brain. Despite the ever-increasing sophistication of methodology in neuroscience and human brain imaging, the brain remains relatively impenetrable compared to other organs of the body. Sometimes psychiatrists and neurologists who are specialists in brain disorders think that even black holes in outer space are easier to study than the human brain. When something pops up that seems to make sense, scientists grab hold and invest all their time and money to study it in every possible aspect.

         This of course runs the risk of overlooking other areas that might be more fruitful for scientists to pursue. Fortunately, scientists, perhaps reeling from all the failures of anti-amyloid drugs, finally seem willing to look at other pathways to ameliorate Alzheimer’s disease. As Fillit notes, “More than three in four treatments currently in clinical development work against non-amyloid targets.  These include drugs to reduce inflammation in the brain, improve blood flow, clear misfolded proteins, improve how the brain metabolizes energy, and more.” In fact, scientists have long known that there are multiple things wrong with the brains of people with Alzheimer’s disease besides the accumulation of amyloid plaques. Amyloid plaques might even be a reaction to one of these other disease processes. For example, Alzheimer himself identified another abnormal protein in the Alzheimer’s disease brain, called hyperphosphorylated tau protein. Misfolded tau proteins form what are called neurofibrillary tangles that collect inside of neurons and may be more central to the cause of Alzheimer’s disease than amyloid plaques. Drugs that rid the brain of neurofibrillary tangles are now under investigation.

         There is also strong interest in the likelihood that Alzheimer’s disease involves some abnormalities in the brain’s blood circulatory or vascular system. This is because many of the same factors that increase the risk for heart disease and stroke also appear to increase the risk for Alzheimer’s disease, including high blood pressure (hypertension), elevated cholesterol levels, smoking, diabetes, and obesity. Exercise and healthy diets may help reduce cognitive decline. So might social engagement and mentally challenging pursuits.

         Scientists, like everyone else, can have trouble abandoning what seems like a very good idea, even when experience should be telling us it is time to move on. In the case of anti-amyloid drugs, so much money has been invested in researching them and so many scientific careers devoted to their biology that moving on to new areas of work has clearly been difficult. Yet it seems it is time to do so. Unless we are surprised by an anti-amyloid drug that really shows strong clinical evidence for being effective, the FDA should stop approving drugs that target amyloid plaque proteins and the NIH and other funding bodies should begin to switch their grant-making priorities to other, more promising avenues. It is time to acknowledge that just because there happens to be a streetlight at one spot along a long block doesn’t mean that’s where our lost keys are to be found.

A surprising trend among some doctors is harming the American public.

Physicians are sometimes thought to be on the front lines of fighting medical misinformation because they are in the advantageous position of interacting very closely with a wide range of patients. Lately, some physicians have even taken to debunking medical misinformation online, and in some cases, unfortunately, they are even attacked on social media. Some estimates suggest that as many as 1 in 4 physicians who address medical misinformation on social media are attacked in response. Renewed efforts have focused on training physicians to respond in a calm, effective manner when this happens. 

But what if the physicians themselves are spreading disinformation? This is actually not as unusual as it might sound. In June of 2022, the American Medical Association deemed it enough of a problem to adopt a new policy. The policy includes measures such as educating physicians to be debunkers of disinformation and educating the American public to recognize disinformation. Many of the action steps in this policy are unfortunately vague, such as “address disinformation disseminated by health professionals via social media platforms and address the monetization of spreading disinformation on social media platforms” and “consider the role of health professional societies in serving as appropriate fact-checking entities for health-related information disseminated by various media platforms.” 

The most important provision in the policy has to do with the power of state medical boards to take disciplinary action when doctors spread disinformation. But more needs to be done here: a coordinated effort between states and medical societies like the AMA is needed to identify and have a clear set of disciplinary actions in place for doctor-led disinformation. Some form of surveillance mechanism and set of clear and consistent disciplinary actions for various types of actions involving disinformation need to be established. This process should be led by the AMA. In addition, the general public needs to be better educated about how to spot physician-led disinformation, and, importantly, how to report propagators of this false information to state medical licensing boards. It is probably the case that most members of the American public would not know how to do this. 

Importantly, we need more information about the motivation behind the spread of disinformation among doctors and the methods that can be used to control the spread of this information online. As many have noted, a lot of physician-led disinformation can be traced back to just 12 individuals, who are often called the “Disinformation Dozen.” The Disinformation Dozen is responsible for 65% of the false anti-vaccine information shared on social media surrounding the COVID-19 vaccines in particular. While not all of them are physicians, some certainly are and have been peddling false information about vaccines and other topics on Facebook for years while often selling supplements and other products. The question then arises as to why Facebook is only now beginning to take down some of their accounts and why they are taking action so slowly, banning some of them but not all of them. Facebook is probably in the best position to surveil where disinformation is coming from on the platform and should be much more active in banning people who become superspreaders. While many have posited that profit is what is mostly behind the Disinformation Dozen’s and others’ spread of lies about health and medicine, there are probably also potent ideological and political motivations here as well. We should not dismiss the possibility that these may be the primary motives in many cases and that some physicians are leading a coordinated attack on our democratic values and our sense of who and what we can trust. 

Finally, what does it mean for physicians and other members of society to become adept at dispelling disinformation? These claims can be quite powerful and are not always so easily “debunked.” We suggest that physicians be trained in various methods of dismantling mis- and disinformation, such as motivational interviewing, prebunking, and inoculation methods. These and other sophisticated methods that exist in the now vast literature on misinformation should be something that all doctors can call upon as they encounter dis- and misinformation online and in the clinic. The AMA should be at the center of this effort as well as efforts to surveil social media for signs of viral disinformation if they are truly serious about doing something about this terrible problem.