This Week in Mental Health Research

By Tom Insel, MD

Greetings Research Roundup readers. Here’s what’s happening in mental health research this week. Surprising to learn that hospitalizations for eating disorders increased so much during the pandemic. And inspiring to see digital innovations for people with serious mental illness. This week was a big one for neuroscience stories, and some of them are fascinating – hope you enjoy. We’re taking a Thanksgiving break next week but will be back with more science stories in December. Enjoy the holiday and read on! (And don’t forget to sign up for our newsletters here.) 

Myelin for Memories

Image: Shutterstock

Sometimes it seems like everything we were taught about the brain is wrong. This week alone, we learn that the brain employs the same subcortical circuit for tool use and language syntax, two functions previously mapped to different regions of the cortex. Neuroscientists in Paris cracked the code on reading by identifying a group of neurons in the ventral visual cortex that distinguish words from other objects. And researchers mapping brain activity in groups of animals found individual cells for recognizing individual group members. But for me, the most amazing story involves myelin.

Myelin, the brain’s white matter, is the insulation that coats nerve fibers or axons in the brain. This insulation supports rapid transmission of nerve impulses down long nerve fibers that can stretch from the top of the brain to the base of the spinal cord. In diseases where this insulation wears out, like multiple sclerosis, nerve cells survive but no longer send information efficiently, so people lose their ability to walk or coordinate movements.

That’s the old story about myelin. The new story is summarized in the journal Science by researchers led by Giulia Bonetto from the Stem Cell Institute at the University of Cambridge. Forget the picture of myelin as the rubber insulation on our electrical cords. A more accurate view is insulation that is constantly changing in response to activity. The cells that produce myelin, oligodendrocytes, rapidly change their activity during learning, laying down memories whether you are learning to juggle or to read.

The weird part is that oligodendrocytes work differently in different parts of the brain to support different kinds of memory. The authors report that spatial memory, emotional memory, and short-term memory are supported by different brain circuits – and distinguished by different roles for myelin. Or, as they put it: “the pattern of myelination is indeed memory system-dependent.”

The implications of this new view are profound. So much of what we have learned about the brain involves “plasticity,” the notion that neurons constantly change in response to experience. But oligodendrocytes are not neurons. They’ve always been considered secondary, a kind of static infrastructure for helping neurons communicate. What if myelin is not just an insulator but an experience-dependent regulator? Bonetto and colleagues say that “dysfunctional myelin or altered myelination during development impairs learning and adaptive behavior” and that “even small changes in myelin across the life span” can impact brain mechanisms involved in cognition and behavior. In other words, our search for the biology of mental illness now needs to include myelin.

Myelin: A gatekeeper of activity-dependent circuit plasticity?  Science Oct 7, 2021

Heartbreak and Heartache: Treating Depression and Heart Failure Together

Astute clinicians have long worried about the combination of depression and heart disease. Heart failure, often following a heart attack, affects over 6 million people in the US and is the leading cause of hospitalizations among Medicare recipients. For reasons that have never been clear, 20% to 40% of people with heart failure develop depression. The two together confer much worse outcomes, impairing quality of life and greatly increasing the risk of cardiovascular death.

So does treating depression improve outcomes for people with heart failure? The research is not consistent. Several large trials with antidepressants showed little impact on hospitalizations or mortality. One approach is to use collaborative care, providing psychological support (with medication as needed) and adding a care manager with back-up from a psychiatrist.

In a large randomized clinical trial, Bruce Rollman and his colleagues at University of Pittsburgh School of Medicine compared the effects of phone-based collaborative care that focused on both depression and heart failure with standard care (which could include referral to specialty mental health care) in people with both disorders. The results were modest: People receiving collaborative care reported better mood but there was no difference in physical functioning, rehospitalization or mortality compared to those receiving standard care.

The modest findings here were a bit disappointing. A classic study of collaborative care for people with depression and diabetes reported better outcomes for both disorders. Perhaps the combination of depression and heart failure is harder to treat, or the collaborative care here was not as robust as in the diabetes study. Whatever the explanation, this trial suggests that phone-based collaborative care can improve people’s mood – but that the combination of heartbreak and heartache are both deadly and tough to treat.

Efficacy of Blended Collaborative Care for Patients With Heart Failure and Comorbid Depression: A Randomized Clinical Trial  JAMA Internal Medicine, Oct 18, 2021

A CORE Innovation for People with Serious Mental Illness

Some 14.2 million Americans (5.6% of adults) have a serious mental illness such as schizophrenia, bipolar disorder and severe mood disorder, according to the latest government statistics. And since January 2020, investors have committed over $5 billion to mental health start-ups, according to the venture capital firm Rock Health. But these two trends are almost completely unrelated: Few of the dollars have gone to create innovations for people with serious mental illness, even though two-thirds of them own smartphones.

Dror Ben-Zeev and his colleagues at University of Washington developed CORE, a game-like daily training that targets negative or dysfunctional thoughts in people with serious mental illness. CORE displays on people’s phones a series of common maladaptive beliefs and nudges them toward less distorted or paranoid thinking. Previous studies showed it reduced negative thoughts and increased resilience. In a new study, Ben-Zeev and colleagues recruited 315 people from 45 states via internet ads, gave them the CORE app and assessed them at 30 and 60 days.

 The CORE intervention: (a) targeted beliefs menu, (b) an example of a maladaptive thought, (c) an educational task.

The results showed again that CORE reduces self-reported symptoms of anxiety and depression. But what’s truly striking is that this study could be done at all. In fully remote studies – meaning there’s no direct, face-to-face interaction between researchers and participants – it’s hard to retain subjects who aren’t mentally ill, especially when they need to perform a self-directed daily task. In this case, more than half of the volunteers dropped out, but 40% remained in the study, using CORE for 30 days. These results suggest that even people with serious mental illness can benefit from innovative treatments and that it’s possible to evaluate these treatments remotely.

A Smartphone Intervention for People with Serious Mental Illness: Fully Remote Randomized Controlled Trial of CORE  JMIR Nov 12, 2021

Increased Hospitalization for Eating Disorders During the Pandemic

Go figure. Rates of hospitalization and outpatient care for people with depression, anxiety, suicidality, and opioid or alcohol use disorders barely changed during the pandemic. But beginning in June 2020, when hospitals were overwhelmed by Covid-19, the rate of hospitalization for eating disorders doubled and remained higher throughout the rest of the year.

Why would more people be hospitalized for eating disorders, especially anorexia nervosa, during the pandemic? This survey of hospital records doesn’t answer that question, but authors David Asch and colleagues at the University of Pennsylvania suggest a few potential reasons: pandemic-inspired food hoarding, contamination fears, concerns about obesity as a risk factor for Covid-19 severity, and even that the return home of college students might have tipped parents off to their eating disorders. Whatever the explanation, one thing is clear: the mental health consequences of this pandemic are complex and unpredictable.

Trends in US Patients Receiving Care for Eating Disorders and Other Common Behavioral Health Conditions Before and During the COVID-19 Pandemic JAMA Network Open, Nov 16, 2021

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.

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