April 22, 2022

By Tom Insel, MD, and Matthew Hirschtritt, MD, MPH

Good morning Research Roundup readers. This was a week with some remarkable reports of new technology: A portable magnetic resonance imaging (MRI) scanner has been developed for use at the bedside, and implantable brain-reading devices are coming to help paralyzed people move and speak. Cool stuff, but not yet ready for prime time.

We do want to call your attention to four prime time stories you might have missed – less cool, perhaps, but important to know. This week, we look at disparities in antidepressant prescriptions based on race, the value of exercise as an antidepressant, and new maps of brain growth in health and disease.  Big surprise for us this week: Firearms are now the leading cause of death in children, in part because we’ve been so successful in reducing car crash fatalities. We love the high-tech breakthroughs, but we need some breakthroughs in policy as well.  

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Firearms Are Now the Leading Cause of Death in Children

Motor vehicle accidents have long been the leading cause of death in children and adolescents. No longer. Guns now cause more deaths in people under the age of 24 years than car crashes, according to a report in the New England Journal of Medicine based on CDC data.

Two opposite trends are at play. Over the past two decades – from 2000 to 2020 – the rate of traffic-related deaths dropped 40% and the rate of firearm-related deaths increased at nearly the same rate.

Image credit/Shutterstock

How to explain these changes? Lois K. Lee and colleagues from Harvard Medical School and the Harvard T. H. Chan School of Public Health focus on the path to success for reducing traffic-related deaths. They describe the comprehensive data systems, support for research, creation of a federal agency responsible for improving safety, and state regulations for booster seats and graduated licensing that collectively reduced fatalities. Overall, they attribute this success to a culture of continuous improvement based on making cars and roads safer.

By contrast, over the past two decades, firearms have become more lethal and there are fewer restrictions on their use. No federal agency is responsible for increasing firearm safety and, according to the authors, “many states have made it easier for children and young adults, as well as adults with criminal records, to gain access to firearms.” There is now a data system to track firearm deaths, but research on the public health impact of firearms has only recently begun to recover from a 23-year blockade of federal funding.

Mortality from Motor Vehicle Crashes and Firearms among Children, Adolescents, and Young Adults, United States, 2000–2020. The rates are age-adjusted and are from the Web-based Injury Statistics Query and Reporting System, Centers for Disease Control and Prevention.

The critical insight from this report is that we can reduce childhood mortality. “As the progress made in reducing deaths from motor vehicle crashes shows, we don’t have to accept the high rate of firearm-related deaths among U.S. children and adolescents,” the authors write. By focusing on safety, data, science and continuous improvement, firearm deaths in children can return to the rate we saw two decades ago. We know how to do this. We just need the commitment.

Crossing Lines — A Change in the Leading Cause of Death among U.S. Children  New England Journal of Medicine April 21, 2022 – Tom Insel


Racial Disparities in Depression Care Persist

It’s well established that white patients are more likely to get appropriate treatment for depression than Latinx and Black patients. But one would hope that the playing field is leveled in a single-payer system like the VA. Surely when all patients with depression have similar medical benefits and receive care in a government-run health care system, everyone is treated the same – right?

Sadly, the answer may be no.

Jocelyn Remmert of the Philadelphia VA Medical Center and colleagues dug into medical-record data from nearly 9,500 veterans with suspected depression who’d been referred by their primary care doctor for integrated treatment for depression from 2015 to 2020. When they entered the program, patients completed a full mental health assessment, which included a depression symptom scale, the PHQ-9.

The researchers then looked back from the time of that referral and saw whether patients were currently prescribed an antidepressant.

Even accounting for various patient characteristics, white patients were nearly twice as likely as Black patients to be prescribed an antidepressant. So maybe white patients were more severely depressed? The data don’t reflect that. Significantly more Black patients than white patients had moderate depression (49.8% versus 45.6%) and severe depression (13.5% versus 10.6%). In fact, white patients with severe depression were still nearly twice as likely as Black patients with severe depression to be prescribed an antidepressant – although the VA guidelines recommend antidepressants (and talk therapy) for all adults with severe depression.

The researchers offer some potential explanations: There may be unaddressed racial bias among primary care doctors; white doctors might not recognize depressive symptoms in Black patients, especially if patients don’t feel comfortable opening up to their doctor; and Black patients might prefer talk therapy over medications. It’s also important to note that these data come from primary care clinics, not from psychiatrist prescribing patterns. Furthermore, these data reflect prescriptions only – not recorded use of the medications.

Where do we go from here? Again, the researchers make a few suggestions: Keep close track of prescription trends by patient race to identify and address disparities early. Sort out the relationship between how we measure depression and antidepressant prescription trends. And follow how patients fare after they’re prescribed antidepressants.

These findings “are likely the symptoms of systemic racism in both health care and society at large, ” the researchers write. They are also a call for change in how we think about race.

Racial Disparities in Prescription of Antidepressants Among U.S. Veterans Referred to Behavioral Health Care.  Psychiatric Services, April 13, 2022.
– Matthew Hirschtritt


A Growth Chart for the Brain

Tacked up on the wall of just about every pediatrician’s office is a standard growth chart to compare height and weight for children as they develop. Could we have a similar growth chart for the brain? A massive study of brain development just published in Nature appears to be the first draft.

Jacob Seidlitz from the University of Pennsylvania and a large cast of colleagues have collected over 100,000 magnetic resonance imaging (MRI) scans on brains from fetal stages (115 days post-conception) to 100 years of age. The scans measure grey matter volume, white matter volume, subcortical volume, brain surface area, ventricular volume, and cortical thickness. Since thousands of the samples come from patients with mental disorders, and some individuals have multiple scans, the scientists were able to look at diagnostic differences and stability over time.

The results reveal some surprising patterns. Grey matter volume maxes out at age 6, white matter peaks at about age 30, and ventricular volume rises rapidly after age 50. While the data show considerable individual variability, people with ADHD, autism, and schizophrenia show consistent differences from age-matched controls, particularly on subcortical volume. While these data are not ready for individual diagnostic use, they provide a basis for building up deeper sex and age-specific information about normal and abnormal growth patterns.

As massive an undertaking as this is, this project is very much a first draft. It over-represents European and North American populations because of a lack of data from Africa and many other global regions. It mixes data from studies of variable quality. And it is limited to gross anatomical measures rather than specific regions of interest (such as the prefrontal cortex which has been implicated in schizophrenia). Nevertheless, this is an important foundation for an effort that can be built through an open-source platform.

Will pediatricians soon have a reference growth chart for brain volume along with the height and weight graphs? Not likely. In truth, we don’t yet know if brain volume is worth measuring. But this kind of effort builds the database for a “brainspan” – a map of the brain across the lifespan. With this database in hand, new questions and new answers will inevitably emerge.

Brain charts for the human lifespan  Nature, April 6, 2022. –Tom Insel


The walking cure?

It’s well established that exercise helps ease the symptoms of depression. We’re told to stay active, move as often as possible, get those steps in every day to improve our mood. But if we think of exercise (or physical actively more broadly) as a medication, what’s the optimal “dose”? Is there a minimum amount necessary – and, on the flip side, can you get too much of a good thing?

Image: Shutterstock

Lots of studies have tried to answer this “dose” question, but they’ve asked the question in different ways that make it hard to draw a firm conclusion. So Matthew Pearce of the University of Cambridge and colleagues pulled together data from 15 previously published studies from around the world, including a total of about 191,000 participants. Pearce and colleagues created a common language to compare apples to apples by using established values of exercise intensity for different activities – the “marginal metabolic equivalent task hours per week (mMET-h/week)” – which measures energy expended above the body’s resting metabolism (1 MET).

They then multiplied the amount of time spent doing exercise by the mMET values for intensity. Light-intensity physical activity like house cleaning was given a value of 1.5 mMET, moderate activity like a casual stroll was valued at 3.5 mMET, and vigorous activity like speed walking or running was given a value of 7.0 mMET.

After compiling the results of all 15 studies, they found that exercise had a dramatic impact on depressive symptoms and risk of developing major depressive disorder – and the biggest difference was seen when moving from no activity to a little bit of activity. In other words, every bit of physical activity above being a couch potato made a measurable difference. But there’s a catch: More isn’t necessarily better. In fact, after achieving about 8.8 mMET-h/week (that’s about 2.5 hours of brisk walking per week), the effect on depressive symptoms leveled off.

In fact, those who did just half of the recommended level of physical activity (about 1.25 hours of brisk walking) had an 18% lower risk of developing depression than people who had no physical activity. Those who got up to the full 2.5 hours had a 25% lower risk of depression. Using these data, the researchers estimate that a whopping 11.5% of depression cases could be prevented if non-active adults got those 2.5 hours of weekly moderate-to-vigorous physical activity.

Of course, as the authors noted, it might be the depression itself that reduces people’s motivation to move. Therefore these data only suggest an association between lower depression and more physical activity.

Nevertheless, this study adds to our appreciation that there are many ways to reduce depression, many of them nonmedical, including exposure to green spaces, strong social connections, and a healthy diet. It’s also important to keep in mind that even though this study doesn’t show an antidepressant benefit from more than moderate exercise, there are other benefits of higher intensity physical activity, including increased energy and improved health.

Association Between Physical Activity and Risk of Depression: A Systematic Review and Meta-analysis. JAMA Psychiatry, April 13, 2022 – Matthew Hirschtritt


If you or anyone you know is considering suicide, call the National Suicide Prevention Lifeline at 1-800-273-8255. And if you’re a veteran, press 1.



Tom Insel, MD, is a psychiatrist, neuroscientist, and former director of the National Institute of Mental Health (NIMH). He is a donor to MindSite News and chair of its Editorial Advisory Board. Dr. Insel’s financial conflict of interest statement, which includes equity and advisory roles in several early-stage mental health technology companies, can be found here.

Matthew Hirschtritt, MD, MPH, is a clinical psychiatrist with the Permanente Medical Group, Inc., a mental health services researcher with the Division of Research, Kaiser Permanente Northern California, and assistant program director of the Kaiser Permanente Oakland Adult Psychiatry Training Program. His current research focuses on identification and treatment of patients with first-episode psychosis, as well as implementation of a telehealth-based mental health evaluation and referral program.

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