What JAMA Psychiatry’s Top 3 Articles of 2021 Can Teach Us

With the exception of the stock market, it’s tough to describe 2021 without lots of red numbers. The COVID-19 pandemic raged on. Economic, social, and physical tolls mounted around the world. Among the myriad effects of the pandemic, a downturn in global mental health emerged as particularly widespread and severe. This has been labeled a pandemic in and of itself, characterized by high rates of stress, depression, anxiety, and loneliness.

Mental health is uniquely realized for each person. However, large datasets like those from the CDC provide much-needed insights on the scope and the specifics of what changed in 2021. Trends from search engines like Google provide a supplementary understanding of interest in and approaches to mental health solutions (for example, in 2021, searches for “how to maintain mental health” dramatically increased worldwide).

In addition, some medical journals explicitly rank their yearly articles by level of public interest. These lists can grant important insights into themes of emergent scientific interest around specific medical topics.

At the end of December, “The Most Talked About Articles of 2021” were ranked by the JAMA Psychiatry using Altmetric, a scoring program based on traditional and social media mentions of published articles. As a premier journal in the world of peer-reviewed mental health research, JAMA Psychiatry covers a wide variety of scientific topics. Yet this list of the most discussed articles yields especially important insights into interesting and significant mental health themes in 2021.

Here is a countdown of the top three articles on the list, along with information about what their popularity may reveal.

#3. Trends in US Emergency Department Visits for Mental Health, Overdose, and Violence Outcomes Before and During the COVID-19 Pandemic

At the start of the COVID-19 pandemic, links between infection and health outcomes primarily centered on respiratory function. In subsequent years the medical literature substantiated a far broader range of virus-associated health effects.

These disparate physiological outcomes can be seen as the direct results of infection as well as the indirect effects of political, economic, and social changes. Among these associations, worsening mental health appears to be of particular significance.

Published on February 21, JAMA‘s third most talked-about paper of 2021 reviewed nearly 190 million emergency department visits for mental health issues, drug overdoses, suicide attempts, intimate partner violence, and suspected child abuse and neglect. The researchers compared a period of approximately 7 months in 2020 with a similar period in 2019 (pre-pandemic), and found that compared with 2019, there were significantly more emergency room visits for mental health issues, suicidal attempts, and drug overdoses during 2020.

The results of this paper dovetail all too well with subsequent research. This includes a recently published estimate by the CDC of a nearly 30% increase in drug overdose deaths in the U.S. (to more than 100,000) in the period from April 2020 to April 2021 compared with the prior year, and paints a concerning picture of a population struggling to manage mental health complications of the pandemic.

#2. How COVID-19 Affects the Brain

Years into the COVID-19 pandemic, and several variants deep, “typical” symptoms of COVID-19 infection remain elusive. With associated symptoms and outcomes ranging from anosmia — i.e., loss of smell — to stroke, depression, seizures, and brain fog, many have proposed that the virus must affect the central nervous system. An exploration of neurological pathways exploited by the SARS-CoV-2 virus was the subject of the second most popular JAMA Psychiatry article in 2021.

With nearly 170,000 views and the #2 slot on this list, “How COVID-19 Affects the Brain” was published on March 21, and took a look at challenging questions related to COVID-19 and the brain. The short piece explored pathways by which the virus might directly infect brain tissue as well as the more indirect role of inflammatory cascades that could influence brain function. This piece hints at some of the biological underpinnings connecting COVID-19 with mental health conditions.

It’s notable that several of the brain-based molecular pathways described in this paper may be affected not just by direct infection, but also by lifestyle changes occurring during the pandemic.

The subject of this article has been interrogated in a number of articles since this JAMA Psychiatry publication. It remains somewhat unclear exactly which pathways are leveraged by the virus to influence brain function, and to what extent direct infection of the brain is contributing to symptoms. This becomes even more pressing with the millions of people now at potential risk for the neurological symptoms of post-acute COVID or “long COVID.”

#1. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder

The COVID-19 pandemic is now thought to have directly increased the global burden of mental health problems, including anxiety and depression. Yet even prior to the pandemic, mental health treatments often lack efficacy, with conventional antidepressants failing to achieve remission in approximately one third of patients. This reality has been one of the drivers for investigating novel mental health therapeutics including psychedelics.

At over 302,000 views, “Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder” is at the top of JAMA Psychiatry‘s most talked-about articles list for 2021. Unlike the prior two articles, which primarily focus on diagnosis and pathology, this publication directly addresses a potential mental health solution.

This randomized, waiting-list controlled trial involved 24 adults with a diagnosis of major depression at Johns Hopkins University. Participants received the psychedelic psilocybin (the active ingredient in “magic mushrooms”) over two sessions plus supportive psychotherapy.

The researchers found that this therapeutic intervention was associated with rapid improvements in depressive symptoms within 1 day of treatment. The team also recorded major reductions in depression scores in most participants within 1 week of treatment, as well as scores indicative of remission of depression in over half of participants 4 weeks after the intervention.

While this is a smaller study, it expanded the existing research around psychedelics (specifically psilocybin) for management of depression. It’s notable that in April 2021, the New England Journal of Medicine published another highly publicized article on the topic, “Trial of Psilocybin versus Escitalopram for Depression,” a double-blinded randomized, controlled trial comparing the effects of psilocybin alone with psilocybin plus the antidepressant escitalopram, finding no differences in antidepressant effects.

Although the data are preliminary, they open the door further for consideration of psychedelics as efficacious mental health interventions. This potential further expands when considering recent research around therapeutics like methylenedioxymethamphetamine (MDMA) for post-traumatic stress disorder.

Putting it Together

JAMA Psychiatry‘s top articles of 2021 demonstrate a pronounced interest on the internally and externally visible mental health effects of the COVID-19 pandemic as well as psychedelic medicine as a potential mental health solution. While much has changed over the course of 2021, every indication is that the pandemic-related surge in mental health issues will remain a major concern in the year to come.

An emphasis on both the brain biology influenced by the pandemic and how unconventional therapeutics like psilocybin could target these pathways are likely to persist as both public and academic themes of significance in 2022.

Austin Perlmutter, MD, is a board-certified internal medicine physician and New York Times bestselling author. He received his medical degree from the University of Miami and completed his internal medicine residency at Oregon Health and Science University in Portland. His focus is in helping others to improve decision-making and quality of life. He is co-author of Brain Wash: Detox Your Mind for Clearer Thinking, Deeper Relationships, and Lasting Happiness; writes for Psychology Today on his blog, The Modern Brain; and is a contributing writer to several health and wellness websites.