May 20, 2022

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

Good morning, Research Roundup readers. With Matt away on vacation this week, I’ve brought you three very different stories for the Roundup. One suggests that the long-term prognosis for someone who experiences an episode of psychosis might be better than we think. Another shows that peers might be better than medical personnel for delivering suicide prevention messages in the emergency room. And a third is a landmark paper tying REM sleep to the consolidation of emotional memories. Hope you find these interesting.

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Perchance to Dream: REM Sleep for Emotional Memories

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In 1953, Eugene Aserinsky hooked up his own 8-year-old son, Armond, to a brain-wave machine at the University of Chicago and tried to stay awake as Armond slept. When he noticed late in the night that the needles tracking Armond’s eye movements and those tracking his brain activity were moving furiously – even though the boy was still sleeping – it led to a pathbreaking discovery: the phenomenon of REM sleep.

Ever since Aserinsky’s two-page paper in Science in 1953, describing this previously unknown phase of sleep, scientists have debated what happens during the REM phase. In addition to eye movements, REM sleep brings a state of temporary paralysis, sometimes accompanied by involuntary muscle twitching. Surprisingly, despite the paralysis, heart and breathing rates reach almost the same levels as when people are awake. We now know that REM sleep makes up about a quarter of an adult’s sleep time – much more in babies – and occurs more frequently later in the night. People who wake up during REM sleep often report vivid dreams.

For decades, scientists have debated not only what happens during REM sleep, but why virtually all mammals have this dream-associated sleep stage. One school of thought has argued that REM sleep is critical for consolidating memories – and this research just received a big boost with a breakthrough paper. Mattia Aime from the University of Bern and colleagues (writing, once again, in Science) described how they manipulated brain microcircuits in the prefrontal cortex of mice to understand how emotional memories can be consolidated during REM sleep.

This research used two powerful sets of tools. One, called two photon calcium imaging, revealed the specific cells and connections that are activated in the prefrontal cortex during REM sleep. A remarkable decoupling of connections – actual, if temporary, structural change – could be seen in this microcircuit during the REM phase. Changes occurring in the microcircuit are a form of neural plasticity, and the fact that they occur during the REM sleep phase suggests that something about REM sleep is facilitating this process.

In the second approach, Aime’s team trained mice to respond to danger by playing an auditory tone while shocking their feet; a different tone was not accompanied by shocks and signaled safety. When the researchers experimentally decoupled the connections in the circuit though use of optogenetics – a technique that uses light to activate cells – but in this case timed to happen only during REM sleep. Activation of this microcircuit enhanced the mice’s memories of the danger and safety signals. By contrast, inhibiting the same microcircuit reduced retention of this memory.

This research demonstrates that REM sleep has an essential role not only in the consolidation of memory but specifically in the consolidation of memories associated with danger and safety signals – which is probably analogous to emotional learning in humans. The identification of the specific cells and connections for this process opens up a new focus for understanding how, where, and when emotions are processed by revealing the location and some of the key factors that mediate the process. This research may not reveal why we dream but it takes us further along the path of understanding how.

Paradoxical somatodendritic decoupling supports cortical plasticity during REM sleep   Science May 13, 2022

Peers for Fears: Are Peers the Best Messengers for Suicide Prevention?

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The role of peers, people with lived experience, has been growing in nearly every aspect of mental health care. Peers not only represent a new workforce that can supplement teams of professionals, they bring a depth of experience and cultural competence to the team that allows them to communicate with and engage people who distrust the mental health care system.

A pilot study in an emergency room setting suggests an additional benefit of including peers. Michael P. Wilson and colleagues from the University of Arkansas for Medical Sciences wanted to see who could best deliver information to suicidal patients about ways to create a safety plan – health providers, or peers with personal experience thinking about or attempting suicide. A standard protocol for safety planning was used by both groups to assess whether the patients had access to weapons or other means of suicide and to identify coping skills and social supports that can reduce suicide.

So were the peers as effective as professional health providers? Follow-up showed that emergency room patients who were seen by peers had similar lengths of stay in the ER and similar acceptance of safety-planning concepts as those who were seen by professionals. But the patients ranked the completeness and quality of the safety plan higher when it was done by peers. And a three month follow-up revealed a lower rate of subsequent emergency room visits in the patients who’d been seen by peers.

While this is a small study (only 31 participants), it is important. Most suicide assessment and safety planning falls to emergency room nurses and physicians who have neither the time nor the training to complete the 25-minute standardized safety planning instrument. Mental health providers may not be available, particularly on the night shifts when many people with suicidal ideation come to the emergency room. If these pilot results can be replicated, using peers to work with patients going through a mental health crisis in an emergency room could prove to be an effective and scalable way to reduce suicide. And no doubt this work will be helpful for peers as well.

Feasibility of Peer-Delivered Suicide Safety Planning in the Emergency Department: Results From a Pilot Trial  Psychiatric Services, May 3, 2022

Psychosis isn’t destiny

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Many people think of psychotic illnesses, such as schizophrenia, as lifelong sources of disability and consider recovery to be unlikely. A new study from Victor Peralta and his colleagues from Pamplona, Spain, tells a more hopeful story.

Peralta and colleagues assessed recovery in 243 people after a mean of 21 years of follow-up. The team measured recovery from standardized ratings using three different criteria: symptomatic, functional, and personal. Personal recovery was defined as establishing an identity, finding meaning in life, taking responsibility for recovery, and having a sense of purpose and hope.

Overall, nearly three-quarters met at least one of the criteria of recovery – a surprisingly impressive number. But there are three domains to recovery and only about one-third met criteria for all of them, while 44% achieved both symptomatic and personal recovery, and half achieved personal recovery alone.

What predicted recovery? Having parents with low incomes and a family history of schizophrenia were negative predictors, and so was a personal history of developmental delay, childhood adversity, and mild drug use. Neurological symptoms such as tremors predicted lower levels of functional recovery and completion of high school predicted higher rates of personal recovery.  Surprisingly, the precise diagnosis (schizophrenia vs bipolar etc.), the precise symptoms a person experienced during their first episode of psychosis, and duration of untreated psychosis didn’t predict whether people recovered 21 years later.

One important caveat of this study is that fewer than half of the people in the original sample were available for follow-up after 21 years. About 20% refused to participate, 17% were deceased, and some could not be located. So, the high rates of recovery need to be tempered by the likelihood of premature mortality and the possibility that many who did not participate had more dire outcomes. Still, this long-term study provides additional evidence that psychosis is an event not a fate.

Long-Term Outcomes of First-Admission Psychosis: A Naturalistic 21-Year

Follow-Up Study of Symptomatic, Functional and Personal Recovery and Their Baseline Predictors  Schizophrenia Bull, May 7, 2022

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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