March 4, 2022

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

Good morning, Research Roundup readers. It’s been an historic week for mental health advocacy with a bold plan released by the White House and President Biden, in his State of the Union address, calling on us to “take on mental health” and “beat the opioid epidemic.” His cross-government approach to behavioral health is unprecedented but it begs the question of how all of these initiatives will be coordinated. Do we need a behavioral health coordinator in the White House? Who will be accountable? But beyond the how and the who questions, there is remarkable agreement on what needs to get done.

Our summaries this week are relevant to some of the issues identified in the White House strategy: The landscape of mental illness and mental health services in children, the high rates of adverse childhood experiences in LGBTQ adults, and findings from studies of early psychosis that are cautionary in some cases and encouraging in others. Read on!

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Do Antipsychotics Impair Cognitive Functioning in Early Psychosis?

Every year in the U.S., about 100,000 young people will experience a first episode of psychosis, which can include hallucinations, paranoia, delusions, disordered speech and behavior, and significant impairment at home and school. The strongest predictor of long-term outcomes for youth with first-episode psychosis is the duration of untreated psychosis – that is, the length of time from the first onset of psychotic symptoms to the start of treatment. In general, the shorter the time someone goes without treatment, the better their outcome.

Antipsychotics are a key part of a multi-pronged approach to treatment but now a new, pre-peer reviewed report suggests that antipsychotics may cause specific cognitive impairments in youth with first-episode psychosis who are treated with them.

In a study led by Kelly Allott from the University of Melbourne, youth who had experienced a first episode of psychosis no more than six months earlier, and had never taken an antipsychotic, were randomly assigned to two groups. For six months, one group was given a commonly used antipsychotic (risperidone or paliperidone) and the other got a placebo. Both groups got intensive psychosocial therapy. The researchers also recruited a group of healthy youth for comparison.

Over the six-month period, the working memory, attention, and processing speed of all three groups stayed the same or got better on most tests. But there were some exceptions. Two tests measured people’s ability to immediately recall word pairs (a measure of verbal learning), and to recall a word they’d previously been exposed to, after receiving a cue that might remind them of it (a measure of working memory).

On these tests, the young people who got placebos and those who were healthy and got no treatment improved, while the youth taking antipsychotics deteriorated. The effect sizes of these differences ranged from medium to large. This is a striking finding since verbal learning and memory are two cognitive functions that often need to be strengthened to help someone recover from psychosis.

In one way, these findings aren’t surprising. The underlying clinical trial from which these data were drawn also produced unexpected results: During the six months of the trial, the youth who got placebos and those who got antipsychotics had similar improvement in their social and occupational functioning.

From those results, one might conclude that antipsychotics aren’t necessary to treat first-episode psychosis. But the authors note that all the patients were supported by a specialized early intervention service and had relatively short periods of untreated psychosis – a rarity among people who develop psychotic illness.

This current study suggests that – as with any powerful treatment – there can be real downsides to antipsychotics. Just as a splint helps a broken bone heal correctly, it also leads to muscle wasting. This study may help prescribers better inform patients and their families about the potential benefits and adverse effects of current antipsychotics and it reminds us of the need to develop medications that do not impair cognition.

Antipsychotic Effects on Longitudinal Cognitive Functioning in First-Episode Psychosis. medRxiv (pre-peer review manuscript), February 21, 2022.

– Matthew Hirschtritt


LGBTQ People Are More Likely to Experience Early Adversity

It’s well established that LGBTQ youth are more likely to be bullied than straight youth, and that youth who are bullied are more likely to seek out mental health services and experience psychiatric distress as adults. Beyond bullying, LGBTQ youth face stressors like family rejection and homelessness at higher rates than heterosexual youth.

Illustration: Shutterstock

Now a new study using nationally representative survey data shows that LGBTQ adults are far more likely than heterosexual adults to have experienced adverse childhood experiences (ACEs) such as witnessing or directly experiencing violence, neglect or abuse. Vanderbilt University PhD candidate Nathaniel Tran and colleagues used data from the 2019 Behavioral Risk Factor Surveillance System to examine self-reported ACEs among adults residing in eight Southern and Midwestern states.

Of the nearly 7% of respondents who identified as LGBTQ, 52% reported three or more ACEs – twice as many as the 26% of heterosexual adults with an ACE score of tree or more. LGBTQ adults were also more likely to report specific ACEs including family substance misuse, mental illness, incarceration, and physical, emotional, and sexual abuse. As adults, the LGBTQ people surveyed had nearly a three-fold increased risk of experiencing frequent mental distress in which at least half the days in the past month were “bad mental health” days.

Given the dramatic impact that ACEs have on mental and physical well-being in adulthood, these results are striking. Designing interventions to prevent and address ACEs among LGBTQ youth has the potential to reap significant benefits for this diverse and vulnerable population when they reach adulthood. There is no evidence that exposure to ACEs influences one’s sexual orientation or gender identity, but there is growing evidence that early adversity helps explain why LGBTQ youth experience higher levels of adverse mental health outcomes. Strategies to prevent and mitigate ACEs – like increasing family economic support, teaching coping skills to youth, training clinicians to better understand and address the needs of LGBTQ youth and connecting youth with caring adult mentors – should be tailored to fit their unique needs.

Early Intervention for First Episode Psychosis is Cost-Effective

Programs that intervene early to provide treatment for young people experiencing their first episode of psychosis have been found to be clinically effective. Programs like the Coordinated Specialty Care (CSC) model, now used in more than 240 clinics in the U.S., reduce overall symptom severity, prevent hospitalization, and improve educational achievement and employment. But compared to standard care that uses only medications, these interventions require a broad array of psychosocial supports, leading payers to ask: Are they cost effective?

To answer that question, Saadia Sediqzadah from the University of Toronto and colleagues created a computer model that projected hospitalizations, employment, and other outcomes for a group of 20-year-old men with first-episode psychosis that developed into schizophrenia. The early intervention strategy employed for this simulation involved a specialized clinic with an emphasis on medication management and psychosocial support. In addition to seeing a psychiatrist, the imaginary patient was assigned a case manager who provided psychosocial support such as securing employment or enrolling in school. This early intervention strategy was compared to standard care that provided treatment in a general psychiatric clinic with medication management but no case management or psychosocial support.

Compared with patients receiving standard care, patients in the early intervention strategy had 3.2 fewer hospitalizations over the course of their projected lifetimes and a consequent reduction in health care costs. One of the strengths of this study was inclusion of cost factors related to outcomes outside of health care. Patients in the early intervention strategy had 2.7 more years of employment over the course of their lives compared with the standard care group. Together, the reduction of health care costs and the increased productivity provide a strong case for the cost-effectiveness of early intervention strategies.

Because early intervention programs like the CSC model are relatively new, there is little data on their long-term outcomes, constraining researchers’ ability to conduct robust modeling studies. But studies based on older models do provide useful guidelines for understanding what should and should not be paid for, and they help focus the field on collecting relevant data to inform reimbursement decisions.

In this case, there is strong evidence that early intervention is clinically effective. This computer model suggests that the evidence of its cost-effectiveness is also strong, but real-world data will be essential for quantifying both benefits and costs.

Cost-Effectiveness of Early Intervention in Psychosis: A Modeling Study Psychiatric Services Feb 23, 2022

-Tom Insel

New Numbers for Mental Health Conditions in Children

The mental health struggles of children and youth have been getting a lot of attention lately. The Surgeon General released an advisory, several professional groups declared a national emergency, and the president’s new mental health strategy calls out the particular needs of children. So how severe is the problem?

A new report from the CDC pulls together data from nine surveillance systems to estimate the magnitude of children’s mental health needs and services prior to the pandemic. From 2013 to 2019, the most prevalent disorders were attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders, affecting about one in 11 children from ages 3 to 17. Among adolescents (ages 12 to 17), roughly one in five had experienced depression. Nearly the same number of high school students had seriously considered suicide, with about seven in 100,000 dying by suicide in 2019.

While a popular narrative is that America’s children are overmedicated, the surveillance data tell a different story. For children ages 3 to 17, roughly 10% had received mental health services and fewer than 8% had received medication. Beneath these figures hides a striking regional variation in services. For example, the receipt of mental health services among adolescents ranged from 15.9% in Tennessee to 35.9% in Colorado. And medication use ranged from 3.7% in California and Nevada to 12.4% in Louisiana.

Perhaps most interesting, this report documents the differences across populations. Children living in households with the lowest income level – those at or below 100% of the federal poverty level – had the highest prevalence of ADHD, behavior or conduct problems, depression, and anxiety, as well as the greatest use of mental health services. Of all racial and ethnic groups, Asian children were least likely to receive services. And American Indian/Alaskan Native children were at the highest risk of suicide by far.

This CDC report does not cover the effects of the pandemic, but it serves as an essential baseline for assessing the impact of the past two years. By combining several surveillance systems, the CDC team has provided a unique overview of the prevalence of disorders and the patterns of service use from 2013 to 2019. It is clear that America’s children, especially those from the poorest families, had high rates of mental health problems and, in many regions, low rates of treatment. Against this background, we will be better able to assess the pandemic’s effect on the mental health of our children.

Mental Health Surveillance Among Children — United States, 2013–2019  Morbidity and Mortality Weekly Report, Feb 25, 2022

–Tom Insel


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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