Hello Research Roundup readers! You may have heard about optogenetics, a technique that uses flashes of light to stimulate individual neurons. Now we have sonogenetics, which uses ultrasound to do the same thing. It’s still in its infancy but a new report shows that ultrasound can activate specific cells in the mouse cortex, introducing yet another approach to modifying circuits in the brain. The other research we’re highlighting this week is closer to implementation ­– a look at studies of family support for people with schizophrenia, opiates in teens and, believe it or not, how step counts correlate with cognition. And, during this Winter Olympics, we couldn’t resist including a paper about American exceptionalism – but one that’s nothing to cheer about. Read on!

Try a Little Help from Your Family

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Traditionally, families were blamed and shamed when someone developed a mental illness. More recently, families have been seen as part of the solution – people whose support and assistance could be enlisted in the recovery process. Specific family interventions have found their place in the clinic, particularly for helping people with schizophrenia avoid relapsing. But not everyone receives family interventions because many people with schizophrenia are estranged from their families. And when family interventions are not covered by insurance, they may not be included in a treatment plan. Now a new analysis of 90 randomized control trials with over 10,000 patients shows us the power – and potential – of family interventions.

Alessandro Rodolico, Irene Bighelli and a group of Italian, German and Japanese researchers undertook a massive meta-analysis to compare 11 different family interventions. When patients get standard treatment – which, for most, is just medication ­– about 37% would be expected to relapse within 12 months. But family interventions overall cut the relapse rate in half. Surprisingly, the simplest intervention, family psychoeducation, which teaches families about the illness without engaging them in specific skill training or psychotherapy, was found to be the most effective, reducing the relapse rate to 10%.

Meta-analytic studies such as this can be biased by giving weak evidence as much weight as strong evidence. And these analyses often struggle with inconsistent data sources since few studies use the same measures collected at the same time points. But every now and then a meta-analysis comes along with such clear findings that the evidence is both consistent and compelling. This is such a study. It demonstrates clearly that family interventions are powerful tools that can help people recovering from psychosis fend off a relapse and shows they should be more widely used. If family psychoeducation were a drug, it would be a blockbuster.

Family interventions for relapse prevention in schizophrenia: a systematic review and network meta-analysis  Lancet Psychiatry, Jan. 27, 2022

-Tom Insel

The Downside of American Exceptionalism

Nobel Laureates Anne Case and Angus Deaton introduced the term deaths of despair to capture with a single number of mortality due to suicide, drug overdoses, and alcohol addiction. They described how these deaths of despair have increased over the past two decades, particularly among white adults without a college education living in rural parts of the U.S. Another recent report, by the National Academy of Sciences, notes that the rising rates of deaths of despair in the U.S. stand in stark contrast to 16 other wealthy nations – including in Western Europe, Canada, Australia, and Japan – where mortality is falling.

Why this striking difference in mortality between the U.S. and other wealthy nations? Peter Sterling and Michael Platt of the University of Pennsylvania take insights from neuroscience and anthropology to try to answer this question. They point to an evolutionary need for social support at all stages of the life cycle. Losing that support, they explain, leads to despair and addiction. Other wealthy nations provide support in the form of prenatal care, parental leave, universal preschool, free education, and paid time off,  and these reinforcements, in the authors’ view, better protect people from deaths of despair.

Deaths of Despair Rise Steeply in US vs Western Europe, Canada, Australia, and Japan. Source: JAMA Psychiatry

Reducing deaths of despair in the U.S. might not be entirely ­– or even primarily ­– the role of the health care system, Sterling and Platt suggest. In fact, the “medicalization of every identified cause of rising mortality” is actually an obstacle,” they write. “Every symptom of despair has been defined as a disorder or dysregulation within the individual. This incorrectly frames the problem, forcing individuals to grapple on their own—by learning resilience, self-help, and so on.” What’s needed, they say, are the kinds of social solutions adopted by other wealthy nations that help create community throughout the lifespan.

Why Deaths of Despair Are Increasing in the US and Not Other Industrial Nations—Insights From Neuroscience and Anthropology  JAMA Psychiatry, Feb 2, 2022

-Tom Insel

For People with Schizophrenia, Many Steps May Lead to Clearer Thinking

It’s well established that physical fitness improves brain functioning and reduces depressive symptoms and anxiety. For many people with schizophrenia, cognitive functioning – including the ability to organize and make sense of information – is impaired. A new study suggests that the simple act of walking may help improve cognitive functioning among adults with schizophrenia.

Li-Jung Chen of the National Taiwan University of Sport and colleagues studied 394 adult patients with schizophrenia who were hospitalized in two Taiwanese psychiatric inpatient units. They asked patients to wear accelerometers for one week and then measured several aspects of cognitive function.

The researchers found that there was a significant and positive correlation between the total number of daily steps and attention, processing speed, reaction time, and motor speed – even after accounting for differences between the race and ethnicity of patients and their substance use, body mass index, use of psychotropic medications and the characteristics of their psychiatric illness. There was also an apparent dose effect: Patients who took 5,000 or more steps per day had faster mental processing than those who took fewer. And patients who took even more – at least 7,500 daily steps had better attention, reaction time and motor speed than those in the sub-5,000 step category. Still, these results are correlations – it’s not clear whether the activity boosted cognition or people with better cognition were more likely to be active.

Poor cognitive functioning among people with schizophrenia is common and disabling. Multiple methods of boosting cognitive performance have shown promise, including the use of computer software to boost cognitive processing. This study seems to offer a method that is free, simple, and for many, effective – but one that needs to be proven before it can be seen as a clinical treatment.

Associations between daily steps and cognitive function among inpatients with schizophrenia. BMC Psychiatry, February 4, 2022.

– Matthew Hirschtritt

Do Adolescents Who Use Opioids for Pain Have Higher Suicide Risk?

In the US, suicide consistently ranks among the top three causes of death for adolescents. In recent years, the number of young people taking their lives by intentionally overdosing has increased. Given the potential lethality of opioids, these trends have created concern about the hazards of prescribing opioids for pain to young people. A recent Swedish study may quell some of these fears.

Kimberly Fine of Indiana University-Bloomington and colleagues collected Swedish population-register data on over 1.9 million residents ages 9 to 29 who didn’t have a prior opioid prescription. Using this cohort, they identified people with any opioid prescriptions starting in 2007 and examined diagnosed self-injurious behavior and death by suicide through 2013. The researchers compared opioid initiators (those with new prescriptions) with other adolescents who had no history of opioid prescribing. They then examined suicidal behavior among people who initiated opioid therapy to people who started using NSAIDs, like ibuprofen, for pain.

In the first comparison – between the opioid initiators and other young people under 30 – those who initiated opioid use in the study period had more than double the risk of suicidal behavior. But in the second comparison – between those using opioids and NSAIDs – the difference was minimal: Over the course of five years, those who started opioids for their pain had a 0.3% greater cumulative incidence of suicidal behavior than those who used NSAIDs.

These results suggest that factors other than opioid use are contributing to suicidal behavior. For instance, chronic pain is a risk factor for suicide. Though opioids pose many hazards and should be prescribed judiciously, this study suggests that opioids – in and of themselves – may not substantially contribute to suicide risk among young people.

Note: the CDC announced today that it was releasing new draft guidance on opioid prescribing, updating recommendations from 2016, and would be receiving public comment for the next 60 days.

Initiation of Opioid Prescription and Risk of Suicidal Behavior Among Youth and Young Adults. Pediatrics, February 7, 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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