Study Uncovers No Strong Evidence That Autism Is Linked With Poor Amygdala Connectivity

A systematic analysis of brain imaging data from nearly 500 individuals suggests that a prevailing neurological hypothesis of autism spectrum disorder (ASD)—theorizing that people with ASD have poorer neural connections in certain brain regions relative to those without ASD—may not be accurate. These findings were published in American Journal of Psychiatry.

“Despite enormous effort and interest, the neural basis of autism spectrum disorder … remains poorly understood,” wrote Dorit Kliemann, Ph.D., of the University of Iowa, and colleagues. They noted that the neurobiology of ASD has generally been tested piecemeal, and results have been limited by small sample sizes, the use of imaging data from multiple sites, and unclear data quality.

In their more comprehensive study, Kliemann and colleagues analyzed high-quality functional MRI data from 488 individuals aged 16 to 50 (212 with ASD and the remaining with no psychiatric illness) available via the Autism Brain Imaging Data Exchange. They examined the relative strength of the neural connections emanating from the amygdala among these individuals when they were not actively engaged in any tasks (resting-state connectivity). The amygdala processes emotions and social cues and therefore is a region of interest in ASD research.

The researchers identified no reliable evidence of atypical amygdala connectivity among the ASD group as a whole relative to those without ASD; they also observed that average variation in connectivity among individuals with ASD was about the same as the variation in those without. Kliemann and colleagues found similar results whether they examined connectivity in the amygdala as a whole or just in specific amygdala subregions.

“It is important to note that we do not conclude that amygdala [connectivity] is generally typical in autism. Instead, we conclude that the evidence for atypical [connectivity] of the amygdala in autism is weak at best, and unreliable,” the researchers concluded. They urged continued acquisition and analysis of high-quality data—“an investment worth prioritizing if we are to better understand and delineate the neurobiological substrates of autism.”

For related information, see the Psychiatric News article “Children With Autism, Fragile X Show Distinct Early Brain Changes.”

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Researchers Identify Neurons That Regulate Opioid Analgesia Independent of Euphoria

Researchers have identified and characterized a set of neurons that specifically regulate the pain-relieving effects of opioids and not their euphoric effects, according to a study published today in Science.

“[C]linical management of chronic pain remains a staggering challenge, and opioids remain essential analgesic options,” wrote Michael P. Fatt, Ph.D., of Sweden’s Karolinska Institutet, and colleagues. “However, the reliance on opioid analgesics has contributed to the opioid epidemic. Alternative therapeutic strategies that provide pain relief across different pain conditions are urgently needed.”

Fatt and colleagues employed multiple neuroscience and computational techniques to track and manipulate neuronal activity in mice that had received shots of morphine. The researchers found that pain relief could be controlled by an ensemble of neurons located in a region of the brainstem called the rostral ventromedial medulla (RVM). After being activated by morphine, these RVM neurons communicate with other neurons in the spinal cord and tell them to inhibit incoming pain signals.

The pain inhibition was mediated by a molecule known as brain-derived neurotrophic factor (BDNF). When researchers blocked BDNF activity in the RVM neurons, morphine produced no analgesic effects in mice; however, when they boosted BDNF expression, morphine could relieve pain at low doses that normally have no effect.

“Has the neural substrate for morphine analgesia now been identified? It may be more accurate to say that one neuronal population that can contribute to opioid analgesia has been molecularly characterized,” Caitlynn De Preter, B.S., and Mary M. Heinricher, Ph.D., of Oregon Health and Sciences University, wrote in an accompanying perspective article. They noted that research studies have identified other sites in the brain associated with opioid analgesia.

“However, acknowledging that other circuit elements likely contribute to opioid analgesia does not detract from the findings of Fatt et al.,” De Preter and Heinricher continued. These results and follow-up research will “provide the tools for targeting specific neural circuits to achieve effective pain relief with fewer side effects, potentially identifying targets for nonopioid pain management and the treatment of chronic pain conditions.”

For related information, see the Psychiatric News article “Integrated Behavioral Approaches Show Promise in Treating Pain.”

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School-Based Mindfulness Interventions Show Positive Mental Health Benefits for Students

Mindfulness-based interventions at schools can help students improve their thinking, resilience, emotional regulation and awareness, and overall mental health, according to a literature review in Psychiatric Services.

“As mindfulness interventions become more widely used and extensively studied, they hold promise for fostering student well-being and mitigating the development of mental health conditions over time,” wrote Tina Marshall, Ph.D., of research consulting firm Westat, and colleagues.

The authors conducted a review of research studies on school-based mindfulness interventions published between 2008 and 2022. To be included in the analysis, the intervention had to have mindfulness as its primary focus and include at least two components (for instance, a combination of breathing awareness and awareness of bodily sensations).

Marshall and colleagues rated the interventions according to the level of evidence supporting them. Of the 24 interventions that the researchers identified across 41 studies, three interventions were rated as having a high level of evidence supporting their effectiveness:

• Learning to BREATHE
• Mindfulness in School Project (MiSP)
• Mindfulness-based stress reduction (MBSR)

All three of these interventions incorporated components such as breathing awareness, awareness of bodily sensations, awareness of mental states, emotional self-regulation skills, and adopting a nonjudgmental attitude toward one’s present state. MiSP and MBSR also included seated or slow-walking meditation activities. The studies supporting these interventions were almost entirely conducted with middle or high school students.

Three other interventions—Gaia Program, MindUP, and a program that blended MBSR and mindfulness-based cognitive therapy—had a moderate level of supporting evidence. These interventions had more research with elementary school children and generally had activities to promote kindness, empathy, compassion, or gratitude.

Positive outcomes included significant improvements in executive functioning, resilience, emotion-regulation skills, emotional awareness, and emotional clarity, as well as decreases in internalizing, externalizing, and attention problems; stress; depressive symptoms; self-hostility; expressive suppression; avoidance and fusion; and rumination.

The researchers found that few studies examined outcomes for underserved populations. They noted that, given the positive outcomes, school administrators may choose to integrate these interventions into standard programming for health promotion. “Further research is needed to support decision makers in selecting cost-effective interventions and addressing the needs of students from underserved populations,” the researchers wrote.

For related information, see the Psychiatric News article “Mindfulness Has Parallels to Indigenous Cultural Practices.”

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Cholinesterase Inhibitors May Slow Patients’ Cognitive Decline in Lewy Body Dementia

Patients with dementia with Lewy bodies (DLB) who took cholinesterase inhibitors had significantly slower cognitive decline over five years compared with patients who took memantine or no medication, according to a study published by Alzheimer’s and Dementia.

Hong Xu, Ph.D., of the Karolinska Institutet in Stockholm, Sweden, and colleagues tapped into a Swedish registry on cognitive/dementia disorders to assess 1,095 individuals who were diagnosed with DLB between May 2007 and December 2018. All individuals had taken the Mini-Mental State Examination (MMSE) at the time of diagnosis and were treated within 90 days with a cholinesterase inhibitor (814), memantine (133), or neither (148). Among those treated with a cholinesterase inhibitor, 69% received rivastigmine, 21% received donepezil, and 10% received galantamine.

Researchers analyzed the individuals’ MMSE scores for up to five years, as well as the incidence of major cardiovascular events (hospitalizations for myocardial infarction, congestive heart failure, or stroke) and all-cause mortality for up to 10 years.

Researchers reported the following results:

• The average MMSE score among individuals at baseline was 21.9; after five years, the average MMSE score among those taking cholinesterase inhibitors was 19.81, compared with 9.62 among those taking memantine and 9.61 among those taking neither. A dose-response relationship suggested higher cholinesterase inhibitor doses provided greater cognitive benefits.
• Among individual cholinesterase inhibitors, donepezil and galantamine significantly slowed cognitive decline, but rivastigmine did not. One possible explanation is that rivastigmine users in the study, unlike those taking donepezil or galantamine, did not achieve the recommended dose, researchers said.
• Patients treated with cholinesterase inhibitors had a 34% lower mortality risk during the first year of follow-up compared with those taking no medications; however, these drugs did not reduce long-term risk of major adverse cardiovascular events or death.

Potential limitations of the study include the inherent challenge of accurately diagnosing DLB and a lack of information on patients’ lifestyle habits, frailty, severity of comorbidities, blood pressure, or presence of co-occurring Alzheimer’s disease, all of which could have influenced the findings.

“Our findings shed light on the potential cognitive benefits of [cholinesterase inhibitor] treatment in DLB patients,” the researchers wrote. “Further research is necessary to elucidate the underlying mechanisms and explore potential pleiotropic effects of [cholinesterase inhibitors] on long-term outcomes.”

For related information, see the Psychiatric News article, “New Medication, Staging Criteria Signal a Potential Shift in Alzheimer’s Care.”

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First-Line Antidepressants Linked to Lower Fall Risk in Older Patients With Depression

First-line antidepressants may help lower the risk of falls and fall-related injuries in older patients with depression, according to a study published today in JAMA Network Open.

Grace Hsin-Min Wang, Pharm.D., M.S., of the University of Florida, Gainesville, and colleagues examined claims data amassed from 101,953 Medicare beneficiaries age 65 or older who received a diagnosis of depression in 2017 or 2018.

Overall, 45.2% of the individuals did not receive any treatment for their depression (the control group), while 14.6% received psychotherapy. Among those who were prescribed first-line antidepressants, 9.2% took sertraline, 9% took escitalopram, 4.7% took citalopram, 3.8% took mirtazapine, 3.1% took duloxetine, 2.9% took trazodone, 2.8% took fluoxetine, 2.3% took bupropion, 1.4% took paroxetine, and 1.0% took venlafaxine. To recognize that real-world clinical practice may not involve immediate treatment, the researchers allowed for a 90-day grace period for treatment initiation following depression diagnosis.

The individuals were then followed for one year from the date of diagnosis or until the earliest fall and related injury after diagnosis, death, entry into hospice or a skilled nursing facility, changing to Medicare Advantage, switching or combining their treatments with other treatments, or discontinuing treatment—whichever came first. Falls and related injuries included outcomes such as bone fractures, sprains, strains, dislocations, and superficial skin injuries.

Compared with adults receiving no treatment, those receiving psychotherapy did not demonstrate any increased or decreased risk of falls or related injuries. However, compared with no treatment, taking first-line antidepressants was associated with a lower risk of falls as follows:

• Bupropion and paroxetine: 26% lower risk
• Venlafaxine: 25% lower risk
• Duloxetine, fluoxetine, mirtazapine, and trazodone: 22% lower risk
• Citalopram and sertraline: 19% lower risk
• Escitalopram: 17% lower risk

The researchers noted that their results contradict those of previous studies that suggested antidepressants may increase the risk of falls and related injuries because of anticholinergic side effects such as orthostatic hypotension, sedation, and syncope. They said some potential reasons for these different findings may be that other studies included adults without depression in the control group and did not allow for a grace period for treatment initiation.

“Although there have been concerns about [falls and related injury] risk associated with these treatments in older adults, our findings suggest that standard first-line depression treatments do not exacerbate FRI risk, indicating their safety for initiation in older adults newly diagnosed with depression,” Wang and colleagues wrote. “However, it remains crucial for clinicians to consider the full spectrum of potential adverse effects and customize treatment plans to ensure a balance between effectiveness and risks.”

For related information, see the American Journal of Psychiatry article “Real-World Evidence on Clinical Outcomes of Commonly Used Antidepressants in Older Adults Initiating Antidepressants for Depression: A Nationwide Cohort Study in Denmark.”

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Majority of Americans Believe Schools Play a Vital Role in Youth Mental Health

More than three-quarters of Americans (84%) believe school staff play a crucial role in identifying signs of mental health problems in students, but less than half (45%) believe most school staff have been trained in identifying these concerns, according to the latest Healthy Minds Monthly Poll, commissioned by APA and fielded by Morning Consult.

As children begin to return to school this month, the poll found that Americans are widely supportive of education about mental health in school, with 89% saying that students should be educated about mental health and the same number saying that school staff should participate in mental health trainings. The poll was conducted on July 22, 2024, among a sample of 2,223 adults.

In a statement, APA President Ramaswamy Viswanathan, M.D., Dr.Med.Sc., affirmed the importance of mental health training for school staff. “When school staff and students have access to good quality mental health education, they are more prepared if they or someone they know is struggling,” Viswanathan said. “One of the best things we can do in light of the youth mental health crisis is to give children and teenagers, and the people that are around them most days, the tools to understand what to do if someone isn’t feeling right.”

Respondents to the Healthy Minds poll said they believe cyberbullying/bullying (42%), mental health (32%), and social media (30%) are the most concerning issues negatively affecting K-12 students today. While more than a quarter of parents (29%) are not confident that their school staff has the training to help students with mental health concerns, 82% believe that school staff would initiate a conversation with them about their child’s mental health concerns and 73% believe that staff would refer their child to mental health services if needed.

Almost half (45%) of parents think they should discuss mental health more with their children. Three-fourths of parents (77%) would be comfortable referring their child to mental health services if they noticed a concerning behavior change.

Recently, the APA Foundation implemented a free training program for K-12 school staff called Notice. Talk. Act.^® at School. The curriculum, currently funded by the Substance Abuse and Mental Health Services Administration, educates school staff on the signals of a potential mental health concern and equips them with the confidence to discuss mental health with children and connect them to appropriate resources.

For more information, see the Psychiatric News article “Popular APA Foundation Program Becomes Notice. Talk. Act. at School.”

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Involuntary Commitment for Individuals With SUD Must Balance Benefits, Harm

Civil commitment of individuals with SUD—with or without co-occurring mental illness—must be implemented in a way that maximizes benefits to them while minimizing harm, according to an essay published as part of a “Controversies in Psychiatric Services” column exploring the ethics of involuntary behavioral health treatment in the journal Psychiatric Services.

“Implementation of civil commitment for people with substance use disorder in the United States has historically been characterized by considerable ambivalence and inconsistency, both in legislation and in clinical practice,” wrote Kenneth Minkoff, M.D., at ZiaPartners Inc. in Tucson. Despite this, a growing number of states—37 in all, along with the District of Columbia—have now passed legislation to allow the practice.

Minkoff acknowledged that “the moral argument for such legislation is powerful,” citing the example of an individual with severe opioid use disorder who overdoses, is revived with naloxone by first responders, and immediately wants to use opioids again; or another individual with SUD whose brain has been “so affected by the disease of addiction that they clearly are unable to protect themselves from harm.”

Balanced again those dangers, Minkoff noted, is the fact that “the limited available data on the effectiveness of civil commitment of people with substance use disorder often do not show favorable results.” To combat this, he calls for leaders and experts in the field to craft data-informed guidelines for the involuntary commitment of individuals with SUD.

“These guidelines could begin with targeting specific populations and carefully delineating commitment criteria, length of commitment, types of settings, and appropriate interventions and outcomes,” Minkoff wrote. He suggested that such guidelines “target harm reduction and overdose prevention as goals rather than necessarily serving as the formal commencement of long-term recovery from opioid use disorder.”

Minkoff concluded: “Beginning with small steps with an eye toward maximizing benefits, minimizing avoidable harms, and continually gathering data that can be used to improve involuntary interventions may be better than either doing nothing or implementing involuntary interventions that do not work.”

For more information, see the Psychiatric News article “Harm Reduction Approach to Substance Use Provides Realistic Support for Patients.”

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Resilience and Gratitude Linked to Successful Aging Among Vets With Mental Disorders

Resilience and a strong sense of gratitude were significantly associated with self-reported successful aging among U.S. veterans with depression, anxiety, and/or posttraumatic stress disorder (PTSD), according to a report in the American Journal of Geriatric Psychiatry.

Somatic symptoms, such as pain, were negatively associated with successful aging, but veterans with more somatic symptoms who also had higher degrees of gratitude were significantly more likely to report successful aging, according to the study.

“Given that there are effective positive psychiatry interventions designed to enhance positive psychosocial characteristics such as resilience and gratitude, such interventions may also help promote successful aging in U.S. veterans” with mental disorders, wrote lead author Robert H. Pietrzak, Ph.D., M.P.H., of the National Center for PTSD, VA Connecticut Healthcare System, and colleagues. (Past APA President Dilip Jeste, M.D., is a co-author on the paper.)

The researchers examined the association between self-reported successful aging and a range of psychosocial variables—including resilience, gratitude, somatic complaints, and exercise—among 475 veterans (average age 58.3; 83.1% male) who screened positive for major depressive disorder, generalized anxiety disorder, and/or PTSD as part of the 2019-2020 National Health and Resilience in Veterans Study (NHRVS). Veterans were asked to rate how successfully they were aging on a 10-point scale, from 1 for least successful to 10 for most successful—with successful aging defined as a self-rating of 8.

The researchers assessed resilience using a 10-item version of the Connor-Davidson Resilience Scale and gratitude using the Gratitude Questionnaire – Six Item Form. The latter asks respondents to rate on a 7-point scale how much they agree (1 = strongly disagree, 7 = strongly agree) with such statements as “I have so much in life to be thankful for,” “If I had to list everything that I felt grateful for, it would be a very long list,” and “I am grateful to a wide variety of people.”

One in five (20.6%) veterans rated themselves as aging successfully. Resilience and gratitude were the strongest positive correlates of successful aging, accounting for 38.1% and 32.4% of the variance, respectively. Greater somatic symptoms were most negatively associated with successful aging, accounting for 11.2% of the variance. Respondents who reported that they engaged in strenuous exercise were also more likely to say they were aging successfully.

“Further research is needed to investigate causal relationships between psychosocial factors and successful aging, and to evaluate the efficacy of psychosocial interventions to promote successful aging in U.S. veterans and other populations with common mental disorders,” the authors concluded.

For related information, see the Psychiatric News Special Report “Positive Psychiatry Shines Light on Patients’ Strengths, Wisdom.”

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Florida’s Red Flag Gun Law Results in Decrease in Expected Homicide Rate

Since Florida implemented a red flag gun law, the state’s rate of firearm homicides rose from 4.51 per 100,000 people in 2017 to 5.28 in 2021—while states with similarly conservative gun policies and no red flag laws saw a larger increase, from 4.50 to 6.85 firearm homicides per 100,000 people, according to a study issued in JAMA.

“In response to the 2018 Parkland high school shooting that killed 17 people, Florida’s legislature enacted a red flag law permitting the temporary removal of firearms by law enforcement officers from individuals posing a danger to themselves or others,” wrote Catherine Gimbrone, M.P.H., and Kara E. Rudolph, Ph.D., both at Columbia University Mailman School of Public Health. “Florida is one of the few politically conservative and largely pro-firearm states to pass a law restricting gun ownership.”

Gimbrone and Rudolph mined data from the Centers for Disease Control and Prevention on state-level homicide and suicide mortality rates from 2009 to 2021. They combined data from 2009 to 2021 from 19 states with similarly conservative gun laws that did not have a red flag gun law to create a comparison group, then adjusted for state sociodemographic and economic variables and determined average annual mortality rates.

The researchers reported the following:

• In Florida, the firearm homicide rate rose from 4.51 deaths per 100,000 people in 2017 to 5.28 in 2021; in the comparison group, firearm homicides increased from 4.50 to 6.85.
• Since 2018, 10,965 petitions have been filed under Florida’s red flag gun law, increasing from 1,192 in 2018 to 2,907 in 2022, exceeding those of states with comparable laws.
• From 2019 to 2021, Florida’s red flag law was associated with an 11% reduction in firearm homicide rates, equivalent to 0.73 fewer deaths per 100 000 population per year than comparison states.
• There were no differences from expected mortality rates in Florida’s firearm suicide or non-firearm homicide or suicide.

One limitation of the study is that it cannot definitively attribute the reduction in expected firearm homicide rates to Florida’s red flag law versus other societal changes after the Parkland high school mass shooting. “The magnitude of the estimated association is plausible, given estimates from studies on other gun control legislation,” researchers wrote. “Findings suggest that red flag laws may reduce the growing burden of firearm homicides.”

For more information, see the Psychiatric News article “Better Resident Training About State Gun Laws and Mental Health Needed.”

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Study Finds Increased Suicide Risk in Spouses of People With Cancer

Spouses of people who have cancer have a higher risk of suicide attempt or death by suicide, especially in the first year after the spouse’s diagnosis, a study in JAMA Oncology has found.

Qianwei Liu, M.D., Ph.D., of Southern Medical University in Guangzhou, China, and colleagues compared data from 409,338 spouses of Danish patients diagnosed with cancer with that of 2,046,682 matched individuals whose spouses did not have a cancer diagnosis (the control group). The researchers drew the data from Danish national health registers and the Danish Causes of Death Register from 1986 through 2016. The individuals were followed until they had a first suicide attempt, died by suicide, died by other causes, emigrated, or December 31, 2016—whichever came first. If the spouse of an individual originally in the control group was diagnosed with cancer during follow-up, the individual was shifted to the group whose spouses had cancer.

Compared with individuals in the control group, individuals whose spouses had a cancer diagnosis had a 1.47-fold increased risk of dying by suicide and a 1.28-fold increased risk of having a suicide attempt during follow-up. During the first year after diagnosis, individuals whose spouses had cancer had a 2.56-fold increased risk of dying by suicide and a 1.45-fold increased risk of having a suicide attempt, and their risk of dying by suicide remained elevated throughout follow-up.

“The finding of the highest risk increase of suicide attempt and suicide death during the first year after cancer diagnosis corroborates our study group’s previous findings of the greatest risk increase of psychiatric disorders during the first year after cancer diagnosis among both patients with cancer and their spouses,” Liu and colleagues wrote.

The risk of having a suicide attempt or dying by suicide was higher in individuals with spouses whose cancer was diagnosed at an advanced or unknown stage compared with those whose spouses were diagnosed at an early stage. The researchers noted that this may be attributable to individuals experiencing a greater burden of the disease or a greater fear of the spouse dying.

“A greater burden of the disease may contribute to a higher level of psychological distress of the patient with cancer and a greater need of support and caregiving from their loved ones, particularly the spouse,” the researchers wrote.

For related information, see the APA blog post “‘Nowhere to Turn’: COVID-19 and Caregiver Stress.”

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Early Childhood Tablet Use Linked to Angry Outbursts

Tablet use in early childhood may promote angry outbursts and emotional dysregulation as the child grows, a study in JAMA Pediatrics has found.

Caroline Fitzpatrick, Ph.D., of the Université de Sherbrooke in Québec, and colleagues examined data from 315 children whose parents completed the Children’s Behavior Questionnaire each year from 2020 to 2022, when their children were 3.5, 4.5, and 5.5 years old. The parents also reported on their children’s tablet use.

The children spent an average of 6.5 hours per week (0.92 hours per day) using tablets when they were 3.5 years old, 6.7 hours per week (0.95 hours per day) when they were 4.5 years old, and 7.0 hours per week (1 hour per day) when they were 5.5 years old.

The researchers found that each 69-minute increase in tablet use when the children were 3.5 years old was associated with a 22% increase in expressions of anger and frustration when they were 4.5 years old. In turn, each standard deviation increase in anger and frustration at 4.5 years was associated with an increase of roughly 17 minutes in tablet use at 5.5 years.

“These findings indicate that tablet use can undermine child ability to effectively manage emotions during daily routines,” the researchers wrote. “Furthermore, children who express more anger may come to elicit more digital strategies to temper outbursts.”

The researchers noted prior studies that suggest children learn emotional regulation by watching parental emotional regulation and when parents engage in emotion-focused parenting such as providing emotional coaching. “More frequent child use of tablets could reduce learning opportunities afforded by these mechanisms and undermine the development of emotional regulation strategies,” they wrote.

“Our study suggests that parents be sensitized that tablet use in early childhood can disrupt the ability to manage anger and frustration and lead to increased outbursts in young children,” the researchers concluded.

For related information, see the Psychiatric News article “Slower Development of Young Children May Be Linked to Excess Screen Time.”

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Psychotropic Polypharmacy Rose in Youth With Medicaid Over Five-Year Study

The number of Medicaid-enrolled youth who were treated with three or more psychotropic drug classes at the same time increased from 4.2% to 4.6% between 2015 and 2020, according to a study of claims in one Mid-Atlantic state issued in Psychiatric Services.

“Concurrent use of multiple psychotropic medications, also referred to as polypharmacy, is a safety concern in pediatric psychiatry,” wrote Yueh-Yi Chiang, B.S., University of Maryland School of Pharmacy in Baltimore, and colleagues. “Most states’ Medicaid programs have implemented oversight of psychotropic regimens that involve the prescription of three or more therapeutic classes of medications for youths ages ≤18 years, which has resulted in some evidence of lower medication use.”

Chiang and colleagues put this to the test by examining Medicaid claims data for youths who were taking one or more of six psychotropic medication classes, including antipsychotics, mood stabilizers, antidepressants, anxiolytics, sedatives, and attention-deficit hyperactivity disorder (ADHD) medications, and who had at least 90 continuous days of Medicaid enrollment between 2015 and 2020 in an unnamed Mid-Atlantic state. Researchers looked at the average days per year of psychotropic polypharmacy—defined as concurrent claims for three or more therapeutic classes of psychotropics—as well as the prevalence of various class combinations. Researchers also assessed changes in the number of psychotropic polypharmacy days by year.

Researchers found 541,380 Medicaid-enrolled youths with at least one mental health encounter during the five-year study period. Of the 126,972 who were prescribed at least one psychotropic medication, one-third were Black and one-third were White. The total number of youths prescribed psychotropic polypharmacy increased from 2,259 of 53,569 (4.2%) in 2015 to 2,334 of 50,806 (4.6%) in 2020. In addition, during that same period, the average annual duration of psychotropic polypharmacy increased by more than one week.

Among youth treated with polypharmacy, the vast majority (97%) were prescribed combinations of three psychotropic drug classes; the most common combination was an ADHD medication plus an antipsychotic and an antidepressant. Youths in the sample were prescribed polypharmacy for an average of seven to eight months out of the year.

One limitation of the study was that it relied on Medicaid data from a single state, which may limit its generalizability to other states. “The lack of clinical information in claims data limits our ability to assess treatment decisions, illness severity, and clinical outcomes related to psychotropic polypharmacy,” the authors noted. “…Future studies, possibly incorporating a longitudinal cohort design, are needed to investigate the long-term safety and health outcomes associated with such polypharmacy regimens.”

For related information, see the Focus: The Journal of Lifelong Learning in Psychiatry article “Assessing and Responding to the Trauma of Child Maltreatment.”

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High Rate of Remission, Persistence of Delusions Among Those Who Relapse in FEP Clinic Found

More than 90% of individuals experiencing a first-episode psychosis (FEP) achieved remission within two years, according to a report in JAMA Psychiatry. Among the minority who relapsed, the researchers found that they experienced delusions that were similar to those they had experienced during their initial psychotic episode.

Delusions were centered on fewer specific themes during relapse episodes, indicating that certain core delusional beliefs were consolidated. The findings suggest that “delusions may serve a critical function for individuals who experience them, and their persistence following clinical intervention further indicates how the phenomena are central to a person’s sense of meaning in daily life,” wrote Gil Grunfeld, M.Sc., and colleagues at McGill University.

The researchers analyzed data on 636 consenting subjects (average age 23.8 years; 191 female) with affective or nonaffective FEP, followed for up to two years in an early intervention service for psychosis in Montréal, Quebec, Canada. The primary outcome was positive symptom relapse and remission, including the content and severity of delusions as defined by the Scale for the Assessment of Positive Symptoms. They also sought to understand what proportion experiences delusions during their relapse episode, and the durability of delusional themes across relapses.

A total of 558 individuals (94.4%) achieved remission. Of those, only 182 (32.6%) had a subsequent relapse to a second or later episode of psychosis; a majority of those who relapsed (63.2%) had delusions, with nearly all (90.2%) experiencing delusions that were similar in content to those they experienced during their first psychotic episode. However, most of these presented with only one or two delusion themes during relapse episodes after experiencing three or more themes during their first episode.

The researchers concluded that specialized early intervention services for psychosis can achieve high rates of sustained remission. “However, in this study, the minority of individuals with delusions who later relapsed experienced similar delusion themes during subsequent episodes,” they wrote. “These findings raise important considerations for the conceptualization of delusions and have clinical implications for trajectories of illness and care.”

For related information, see the Psychiatric News article “LAI Antipsychotics Beat Oral Meds for Preventing Relapse, Hospitalization.”

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Buprenoprhine-Naloxone Combo Appears Safe During Pregnancy

Buprenorphine combined with naloxone is just as safe as buprenorphine alone for pregnant individuals with opioid use disorder (OUD), according to a report published yesterday in JAMA. For some complications such as neonatal abstinence syndrome, buprenorphine plus naloxone even appeared as the safer option.

Adding naloxone to buprenorphine is intended to deter diversion, because naloxone prevents buprenorphine’s euphoric effects when people try to take it intranasally or intravenously. “In pregnancy, buprenorphine alone is generally recommended because of limited perinatal safety data on the combination product,” wrote Loreen Straub, M.D., M.S., of Harvard Medical School, and colleagues.

To gain more insight into the risks of the combination product, Straub and colleagues made use of a Medicaid-based dataset that included rich patient-level information on mothers and their infants. They examined a range of maternal and neonatal outcomes among 3,369 pregnant individuals exposed to buprenorphine plus naloxone during the first trimester and 5,326 exposed to buprenorphine alone or who switched from the combination to buprenorphine alone by the end of the first trimester.

Compared with pregnant individuals who took buprenorphine alone, those who took the combination formula had a lower risk of having infants born with neonatal abstinence syndrome (37.4% versus 55.8%), infants who required neonatal intensive care (30.6% versus 34.9%), or infants who were small for their gestational age (10.0% versus 12.4%). The risk of other adverse outcomes, including congenital birth defects, preterm birth, respiratory problems in the infant, or severe maternal health problems post-delivery (such as heart attack or delirium), was similar with either medication type.

“This [study] supports the view that both formulations are reasonable options for treatment of OUD in pregnancy, affirming flexibility in collaborative treatment decision-making,” Straub and colleagues concluded.

For related information, see the American Journal of Psychiatry article “Flexible Buprenorphine/Naloxone Model of Care for Reducing Opioid Use in Individuals With Prescription-Type Opioid Use Disorder: An Open-Label, Pragmatic, Noninferiority Randomized Controlled Trial” and the related editorial “Flexible Buprenorphine/Naloxone Treatment Models: Safe and Effective in Reducing Opioid Use Among Persons With Prescription Opioid Use Disorder.”

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Lykos Therapeutics’ Psychedelic MDMA Not Approved by FDA

Lykos Therapeutics’ submission of midomafetamine (MDMA) capsules for the treatment of posttraumatic stress disorder was rejected Friday by the Food and Drug Administration (FDA), with officials requesting an additional phase 3 study, which will take several years to complete.

This was the FDA’s first decision involving a psychedelic drug used for a psychiatric indication. Lykos said it plans to request a meeting with the FDA to ask for reconsideration of its decision.

“The FDA request for another study is deeply disappointing, not just for all those who dedicated their lives to this pioneering effort, but principally for the millions of Americans with PTSD, along with their loved ones, who have not seen any new treatment options in over two decades," Amy Emerson, Lykos Therapeutics’ CEO, said in a media release.

MDMA, also known as ecstasy, is an entactogen that is believed to increase an individual’s self-awareness and introspection. Lykos’ clinical trials included a novel psychotherapeutic intervention alongside MDMA sessions that Lykos said helps people access and process painful memories, so they can undergo therapy without becoming overwhelmed.

The concerns raised by the FDA in its rejection letter echo those of the agency’s independent Psychopharmacologic Drugs Advisory Committee, which in early June voted overwhelmingly against the approval of MDMA. Advisory committees’ recommendations are nonbinding, but the FDA typically follows them.

Among issues raised by the advisory committee were:

• Lack of evidence of durability of the treatment response.
• Allegations of sponsor/researcher bias and undue influence.
• Expectancy bias stemming from prior illicit use of MDMA by trial participants.
• Insufficient data on cardiovascular and hepatotoxicity risks.
• “Functional unblinding” arising from most researchers and participants correctly guessing who received the placebo versus active treatment.
• The role the psychotherapy played in the trial outcome, and the fact that psychotherapy is not regulated by the FDA.

The committee also focused on a documented case of serious sexual misconduct that occurred during a 2015 phase 2 trial. Notably, the journal Psychopharmacology on Saturday retracted three papers related to these phase 2 studies, noting that the study authors were aware of unethical conduct at one of the study sites but did not disclose that information to the journal or remove data generated by that site from their analysis.

Lykos took issue with what it called the limited number of subject matter experts on the advisory committee and that the discussion at times “veered beyond the scientific content” presented in the briefing documents. Lykos asserted that the FDA’s concerns “can be addressed with existing data, post-approval requirements, or through reference to the scientific literature.”

For more information, see the Psychiatric News article “Psychedelics’ Use as Medicine Hits Significant Roadblock.”

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Community Health Workers Boost Smoking Cessation in Adults With SMI, Study Finds

Adults with serious mental illness (SMI) and tobacco use disorder who engage with community health workers at least once a month are more likely to quit smoking than those with less engagement, according to a report published today in Psychiatric Services.

Community health workers are non-medical staff who assist health care systems by providing a range of support services to patients, including home visits, health education, and first aid.

Cheryl Y. S. Foo, Ph.D., of Massachusetts General Hospital, and colleagues examined data from 196 adults with SMI (such as schizophrenia or bipolar disorder) as well as tobacco use disorder who received community health worker support as part of a clinical trial on smoking cessation. The community health workers visited participants in their homes or neighborhoods, encouraged them to set smoking-cessation goals, educated them about approved therapies, and assisted them with visits to their physician or self-help group. The community health workers also co-led group counseling sessions on smoking cessation alongside a clinically trained professional.

Foo and colleagues found that the participants who had more contact with community health workers—whether via home visits or group counseling sessions—were much more likely to quit smoking after two years compared with adults who had less community health worker engagement.

The optimal “dosage” of community health worker support—factoring in odds of success versus time commitment—was for an adult to have 30 to 65 visits over two years that lasted about 29 to 34 minutes each, as well as attending 20 to 57 group sessions over two years. Further increasing community health worker engagement above these levels only marginally improved tobacco-cessation outcomes, the researchers noted.

“Ideally, implementation of an evidence-based … intervention should strike a balance between the maximally efficacious dose and the dose that is reasonably affordable and feasibly accepted by a large enough proportion of recipients to maximize benefits in real-world settings,” they wrote.

As part of their study, Foo and colleagues also conducted qualitative interviews with patients, primary care physicians, and community health workers. The interviews indicated that the community health workers helped people quit by building trust and holding patients accountable. In addition, they were instrumental in breaking down structural barriers to treatment by helping to schedule appointments, provide transport, and ensuring insurance was up to date.

For related information, see the American Journal of Psychiatry editorial, “Social Determinants of Health and Smoking Cessation: A Challenge.”

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Feelings of Sadness Down, Fears of Violence Up Among High Schoolers

The percentage of high school students who have experienced school-based violence and absenteeism because of safety concerns has risen over the last two years, according to a report by the Centers for Disease Control and Prevention (CDC). However, the same report revealed decreases in the percentage of high school students who feel persistently sad or hopeless and the percentage of students who ever used certain illicit substances.

Researchers in CDC’s Division of Adolescent and School Health compared data from the 2021 and 2023 Youth Risk Behavior Survey. Conducted every two years among a nationally representative sample of U.S. high school students, the survey captures demographic data while also asking the students about their health behaviors and conditions, substance use, and experiences such as school connectedness, unstable housing, and exposure to community violence.

Worsening trends from 2021 to 2023 centered on violence and safety concerns and include:

• Increases in the percentage of students who were bullied at school (from 15% to 19%).
• Increases in the percentage of students who missed school because of safety concerns either at school or on the way to school (from 9% to 13%).
• Increases in the percentage of students who were threatened or injured with a weapon at school (from 7% to 9%).

Female and LGBTQ+ high school students were more likely than their peers to report concerns of violence. Nearly 3 in 10 LGBTQ+ students were bullied at school, while nearly 2 in 10 missed school because of safety concerns.

Key improvements to youth mental health from 2021 to 2023 include:

• Decreases in the percentage of students who experienced persistent feelings of sadness or hopelessness (from 42% to 40%).
• Decreases in the percentage of female students who experienced persistent feelings of sadness or hopelessness (from 57% to 53%) and who seriously considered attempting suicide (from 30% to 27%).
• Decreases in the percentage of Hispanic students who felt persistently sad or hopeless (from 46% to 42%) and who seriously considered attempting suicide (from 22% to 18%).
• Decreases in the percentage of Black students who attempted suicide (from 14% to 10%).
• Decreases in the percentage of students who used illicit substances such as cocaine, inhalants, heroin, methamphetamines, hallucinogens, or ecstasy (from 13% to 10%).
• Decreases in the percentage of students who currently misused prescription opioids (from 6% to 4%).

“These data show that we’ve made some progress in tackling these issues in recent years, which proves that they are not insurmountable. However, there’s still much work ahead,” CDC Division of Adolescent and School Health Director Kathleen Ethier, Ph.D., said in a statement. “Considering the vital role schools play in promoting health and well-being, it is critical to address school-based violence and safety concerns.”

For related info, see the Psychiatric News article, “Stages Preceding School Violence Offer Critical Points of Intervention.”

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TMS More Effective Than Next-Step Antidepressant Treatment, Study Shows

Patients with treatment-resistant depression who received repetitive transcranial magnetic stimulation (rTMS) experienced greater reduction and remission of symptoms than those who received another trial of an antidepressant, according to a report in AJP.

“rTMS should be considered as a viable treatment option at an early stage of the treatment algorithm and may be more effective than antidepressant medication switch or augmentation,” wrote Iris Dalhuisen, Ph.D., of Radboud University Medical Center, the Netherlands, and colleagues.

Eighty-nine patients with unipolar nonpsychotic depression who had not responded to at least two medication trials (including at least one antidepressant) were randomized to receive either rTMS or the usual next treatment as indicated in Dutch practice guidelines.

Patients in the rTMS group received 25 sessions of high-frequency (10 Hz) TMS delivered to the left dorsolateral prefrontal cortex over an eight-week period; rTMS patients could remain on their existing medication. Those receiving treatment as usual either switched their current medication to a tricyclic antidepressant or augmented their current medication with lithium or a second-generation antipsychotic.

All patients also received either group or individual psychotherapy, of a variety of types, at least once a week.

The primary outcome was a change in depression severity based on the Hamilton Depression Rating Scale (HAM-D) after eight weeks. Secondary outcomes included remission rates as well as changes in specific depression-associated symptoms (anhedonia, anxiety, sleep, rumination, and cognitive reactivity).

Patients in the rTMS group experienced an average decrease in HAM-D scores of 10.02 points compared with just 4.19 among those in the medication group. Patients receiving rTMS (27.1%) were also significantly more likely to achieve remission of symptoms compared to those receiving another antidepressant (4.9%). They also experienced a greater reduction in symptoms of anxiety and anhedonia (inability to enjoy normally enjoyable activities).

The authors said analysis of the follow-up results of this ongoing study will be crucial. “Analysis of these data needs to establish what the long-term effectiveness and cost-effectiveness of both treatments is and whether rTMS still outperforms medication after several months,” they wrote. “Our cost-effectiveness analysis will show whether this result can be replicated based on real-world data.”

For related info, see the Psychiatric News article, “TMS Should Be Considered as First-Line Treatment for Moderate to Severe Major Depressive Disorder,” now on Newswire.

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Neuropsychiatric COVID Symptoms Worsen Over Time For Many Patients

People admitted to the hospital for COVID-19 continued to have neuropsychiatric symptoms, including depression, anxiety, cognitive decline, and fatigue, which appeared to worsen over time up to three years post-discharge, according to an article in Lancet Psychiatry.

Maxime Taquet, Ph.D., at the University of Oxford, and colleagues recruited 475 adults who had been hospitalized for COVID-19 at one of 83 participating National Health Service hospitals in the United Kingdom between February 2020 and March 2021; all had been part of a larger earlier study for which they completed various neuropsychiatric testing at six and 12 months post-discharge.

For this study, conducted two to three years post-discharge, participants completed computerized cognitive tests covering eight cognitive domains, as well as separate assessments for depression, anxiety, fatigue, subjective cognitive decline, and occupation status.

“We aimed to assess how cognitive, psychiatric, and fatigue symptoms emerge and evolve over time, to identify which early aspects of COVID-19 illness predict these outcomes, and to establish how symptoms correlate with occupational change,” Taquet and colleagues wrote.

Up to three years after hospitalization, participants had worse cognitive scores than expected based on their sociodemographic factors across all domains tested. About 22% of respondents reported severe depression, about 24% reported severe fatigue, and nearly 25% reported severe cognitive decline.

Psychiatric and cognitive symptoms increased at two to three years post-hospitalization relative to earlier assessments due to both worsening of symptoms already present at six months and emergence of new symptoms. New symptoms occurred mostly in people with other symptoms already present at six months, researchers noted. Researchers also reported that 27% of participants changed occupations, with poor health being the most common reason given. Occupation change was strongly and specifically associated with objective and subjective cognitive deficit.

“Prompt interventions to treat symptoms present in the months after hospital discharge might prevent the emergence of additional symptoms and the development of a more complex syndrome,” Taquet and colleagues concluded. “Interventions promoting cognitive recovery or preventing cognitive decline might limit the occupational impact of SARS-CoV-2 infections, thereby improving functional and economic outcomes of COVID-19 for the individual and society as a whole.”

For related info, see the Psychiatric News article, “Psychiatrists Uniquely Suited for Helping Patients With Long-Haul COVID-19,” now on Newswire.

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Physiotherapy Added to CBT May Boost Quality of Life in Patients With Functional Movement Disorders

Adding physiotherapy to mental health support such as cognitive-behavioral therapy (CBT) may improve the quality of life for people with functional movement disorders, a study in JAMA Neurology has found. Functional movement disorders are a subset of functional neurologic disorder (conversion disorder) and include unusual, involuntary movements or body positions caused by a problem with the way signals are sent throughout the brain.

Daniel Macías-García, M.D., Ph.D., of the University of Seville, and colleagues analyzed data from 38 patients with functional movement disorders who were randomized to receive either physiotherapy plus CBT (the treatment group) or psychological support only (the control group). The treatment group participated in four successive, weekly, one-hour group sessions of CBT and 12 one-hour individualized physiotherapy sessions delivered three times a week. The control group participated in four weekly one-hour group sessions of supportive psychotherapy that included discussion about life stressors.

The researchers measured the patients’ perceived mental and physical quality of life using various surveys at baseline, three months, and five months. At five months, patients in the treatment group reported significantly greater improvements in physical measures of quality of life such as severity of motor symptoms, pain, and perception of overall health compared with the control group.

Also at the fifth month, 47% of patients in the treatment group reported improvement in at least one aspect of quality of life and no worsening in others compared with 16% of patients in the control group.

“[The] effect [of multidisciplinary care] on the physical aspects of quality of life is superior to a comprehensive diagnosis followed by psychoeducation and psychological support, and it seems to be driven by improvements in mobility and pain,” the researchers wrote. “Multidisciplinary treatment may also improve social functioning and may be cost effective regarding return to work; however, further studies with larger cohorts and longer follow-up periods must clarify these aspects.”

For related information, see the Journal of Neuropsychiatry and Clinical Neurosciences article “A Review and Expert Opinion on the Neuropsychiatric Assessment of Motor Functional Neurological Disorders.”

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Shifts in Sexual Minority Identity Associated With Worsening Mental Health

Sexual minority individuals who shift from a monosexual (gay or lesbian) to a plurisexual (bisexual, pansexual, or queer) identity—or vice versa—may be at greater risk of mental health or substance use problems than individuals with static identities, reports a study in the American Journal of Psychiatry.

Evan A. Krueger, Ph.D., of Tulane University in New Orleans, and colleagues examined data from the Generations study, a prospective survey of cisgender sexual minority adults conducted from 2015 to 2016 and again from 2017 to 2018. Among the areas covered at baseline and follow-up were five related to mental health or substance use: overall psychological distress in the past month, poor mental health days in the past month, current social well-being, current drinking frequency, and current use of other drugs.

The study sample included 683 participants, of whom 400 were consistently monosexual, 239 were consistently plurisexual, 19 switched from monosexual to plurisexual, and 25 switched from plurisexual to monosexual between 2015 and 2018. The researchers found the following:

• Females who had recently adopted a plurisexual identity reported higher psychological distress, lower social well-being, and more poor mental health days than consistently monosexual females.
• Males who had recently adopted a monosexual identity reported lower social well-being than consistently plurisexual males.
• Males who recently switched identities in either direction reported more problematic drinking than males who retained a consistent identity; males who switched also reported more problematic drug use than consistently plurisexual males.

“These findings suggest that for [sexual minority] males, substance misuse prevention efforts may need to target individuals actively experiencing an identity change or those who are unsure of their identity,” Krueger and colleagues wrote.

“Importantly, despite identity change being associated with declines in several indicators of behavioral health, these findings do not suggest that efforts to influence one’s identity developmental trajectory would be beneficial for sexual minority behavioral health,” the researchers added. “In fact, ample research has shown that efforts to influence the ways in which sexual minority people identity (e.g., so-called conversion therapy) are harmful to health and well-being.”

For related information, see the Psychiatric Services article “Age-Associated Differences in Mental Distress Among Sexual and Gender Minority Adults.”

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Integrated GPM May Help Adolescents With Borderline Personality, Eating Disorders

Clinicians can use adapted general psychiatric management (GPM) techniques to successfully manage adolescents who have both borderline personality disorder and an eating disorder, according to a report issued in The American Journal of Psychotherapy.

“Although specialized adolescent-focused interventions for borderline personality pathology can be adapted for these individuals, the availability of those treatments is unlikely to meet the public health demand,” wrote Marcos S. Croci, M.D., from the University of São Paulo, Brazil, and colleagues. “Therefore, developing a generalist early intervention is imperative.”

GPM—also known as good psychiatric management—is a treatment for borderline personality disorder that empowers patients through psychoeducation, life-building activities, conservative psychopharmacology, and accountability. Croci and colleagues propose that some best practices for eating disorder treatment can be integrated into the GPM framework and address the core psychopathologies of both disorders.

The researchers call their approach GPM-AED, for general psychiatric management for adolescents with borderline personality disorder and an eating disorder. They said that GPM-AED allows nonspecialists “to help adolescents with borderline personality pathology to build a life independent of eating disorder symptoms… while remaining focused on the assessment and safety considerations that are crucial in caring for these patients.”

This will allow specialized treatments to be reserved for those who do not respond to first-line interventions or for individuals with severe symptoms, according to Croci and colleagues.

General principles of GPM-AED include:

• Provide earlier care: Beginning treatment of borderline personality and eating disorders during adolescence is key, when prognoses are better.
• Disclose diagnoses, engage in psychoeducation: Disclosing diagnosis and sharing knowledge and patient literature about the biology, symptoms, course, treatment, and possible medical complications can help destigmatize these disorders and help patients form a new opinion about them.
• Focus beyond treatment, set goals: Helping patients to invest in life outside of treatment is the primary goal of the therapy, by encouraging them to engage in activities that resonate with their dreams, desires, and values.
• Involve the family as allies: This means instructing parents to serve as allies, schedule mealtimes, avoid difficult conversational topics while eating, not follow a restricted diet, or make comments on the patients’ or others’ eating habits (“fat talk”). Clinicians should avoid blaming the parents.
• Manage safety: Monitoring for suicidality and safety planning are critical because suicide rates among youths with borderline personality disorder and eating disorders are high.
• Refer high-risk patients: Individuals with life-threatening behavior, for example, laxative misuse or vomiting when at low weight, severe malnutrition, rapid weight loss, or weight-restoration failure should be referred to higher levels of care.

For related information, see APA’s draft “Practice Guideline for the Treatment of Patients With Borderline Personality Disorder.”

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