Social Media Cause Depression How heavy Instagram and Facebook use may be affecting kids negatively Quick Read Studies show that depression among teenagers and young adults has gotten more common over the past decade. Social media use has also increased during the same time. It’s hard to say for sure that social media causes depression. Still, there are several ways that using social media could harm kids. Some experts think that connecting with peers online is less emotionally fulfilling than connecting in person. Research shows that teenagers who spend more time on social media also feel more isolated. It could be that kids who already feel isolated use social media more. But it could be that using social media actually makes kids feel isolated. Another theory is that social media is bad for teenagers’ self-esteem. Seeing lots of perfect pictures online might make kids (especially girls) view themselves negatively. Feeling bad about themselves can lead to depression. Social media can also cut into the time that kids spend on activities that make them feel good, like exercise and hobbies. Additionally, it can distract from important tasks like homework. Having to juggle those responsibilities can increase kids’ stress. Studies also suggest that using social media at night interferes with restful sleep for many teenagers. It’s important for parents to check in with kids about their social media use and help them develop healthy habits. You can encourage kids to turn off notifications, spend plenty of time on offline activities that make them feel good, and put phones away before bedtime. You can also set a good example by modeling balance in your own use of social media. Finally, be sure to keep an eye out for signs of depression and get professional help if you’re worried. It’s especially important to check on kids who are under a lot of stress. Full Artilce: Is using social media making our kids unhappy? Evidence is mounting that there is a link between social media and depression. In several studies, teenage and young adult users who spend the most time on Instagram, Facebook and other platforms were shown to have a substantially (from 13 to 66 percent) higher rate of reported depression than those who spent the least time. Does that mean that Instagram and TikTok are actually causing depression? These studies show a correlation, not causation. But it’s worth a serious look at how social media could be affecting teenagers and young adults negatively. One reason the correlation seems more than coincidental is that an increase in depression occurred in tandem with the rise in smartphone use. A 2017 study of over half a million eighth through 12th graders found that the number exhibiting high levels of depressive symptoms increased by 33 percent between 2010 and 2015. In the same period, the suicide rate for girls in that age group increased by 65 percent. Smartphones were introduced in 2007, and by 2015 fully 92 percent of teens and young adults owned a smartphone. The rise in depressive symptoms correlates with smartphone adoption during that period, even when matched year by year, observes the study’s lead author, San Diego State University psychologist Jean Twenge, PhD. Over that same time period there was a sharp spike in reports of students seeking help at college and university counseling centers, principally for depression and anxiety. Visits jumped 30 percent between 2010 and 2015, and they’ve continued to rise since the pandemic. Social media and depression One of the biggest differences in the lives of current teenagers and young adults, compared to earlier generations, is that they spend much less time connecting with their peers in person and more time connecting electronically, principally through social media. Some experts see the rise in depression as evidence that the connections social media users form electronically are less emotionally satisfying, leaving them feeling socially isolated. “The less you are connected with human beings in a deep, empathic way, the less you’re really getting the benefits of a social interaction,” points out Alexandra Hamlet, PsyD, a clinical psychologist. “The more superficial it is, the less likely it’s going to cause you to feel connected, which is something we all need.” Indeed, one exception to the depression correlation is girls who are high users of social media but also keep up a high level of face-to-face social interaction. The Twenge study showed that those girls who interact intensely offline as well as through social media don’t show the increase in depressive symptoms that those who interact less in person do. And there are some teenagers who aren’t successful in connecting with peers offline, because they are isolated geographically or don’t feel accepted in their schools and local communities. For those kids, electronic connection can be lifesaving. Social Media and Perceived Isolation Another study of a national sample of young adults (age 19-32) showed correlation between the time spent on social media and perceived social isolation (PSI). The authors noted that directionality can’t be determined. That is, “Do people feeling socially isolated spend more time on social media, or do more intense users develop PSI?” If it’s the latter, they noted, “Is it because the individual is spending less time on more authentic social experiences that would decrease PSI? Or is it the nature of observing highly curated social feeds that they make you feel more excluded?” Which brings us what we now call FOMO, or fear of missing out. Jerry Bubrick, PhD, a clinical psychologist at the Child Mind Institute, observes that “FOMO is really the fear of not being connected to our social world, and that need to feel connected sometimes trumps whatever’s going on in the actual situation we’re in. The more we use social media, the less we think about being present in the moment.” Instead we might be occupied with worrying why we weren’t invited to a party we’re seeing on Instagram, or making sure we don’t miss a single post from a friend. But if we’re always playing catch-up to endless online updates, we’re prioritizing social interactions that aren’t as emotionally rewarding and can actually make us feel more isolated. Social media and self-esteem Another theory about the increase in depression is the loss of self-esteem, especially in teenage girls, when they compare themselves negatively with artfully curated images of those who appear to be prettier, thinner, more popular and richer. “Many girls are bombarded with their friends posting the most perfect pictures of themselves, or they’re following celebrities and influencers who do a lot of Photoshopping and have makeup and hair teams,” explains Dr. Hamlet. “If that’s their model for what is normal, it can be very hard on their self-confidence.” Indeed, image-driven Instagram shows up in surveys as the platform that most leads young people to report feeling anxiety, depression and worries about body image. Curation of a perfect image may not only make others feel inadequate, it’s unhealthy even for those who appear to be successful at it, notes Dr. Bubrick. “Kids spend so much time on social media trying to post what they think the world will think is a perfect life. Look at how happy I am! Look how beautiful I am! Without that they’re worried that their friends won’t accept them. They’re afraid of being rejected.” And if they are getting positive feedback from their social media accounts, they might worry that what their friends like isn’t the “real” them. Less healthy activity Another possible source of depression may be what teenagers are not doing during while they’re spending time on social media, including physical activity and things that generate a sense of accomplishment, like learning new skills and developing talents. “If you’re spending a lot of time on your phone, you have less time for activities that can build confidence, a sense of achievement and connectedness,” explains Dr. Hamlet. Kids who are spending a lot of time on devices are not getting much in return to make them feel good about themselves, she adds. “Yes, you get a little dopamine burst whenever you get a notification, or a like on a picture, or a follow request. But those things are addicting without being satisfying.” Disrupted concentration Another thing disrupted by social media is the process of doing homework and other tasks that require concentration. It’s become common for teenagers to engage with friends on social media at the same time they are studying. They take pride in being able to multi-task, but evidence shows that it cuts down on learning and performance. “Basically, multitasking isn’t possible,” Dr. Hamlet notes. “What you end up doing is really just switching back and forth between two tasks rather quickly. There is a cost to the brain.” And with poorer concentration and constant interruption, homework takes substantially longer than it should, cutting into free time and adding to stress. Sleep deprivation and depression Some of the ways in which social media use impacts mood may be indirect. For instance, one of the most common contributors to depression in teenagers is sleep deprivation, which can be caused, or exacerbated, by social media. Research shows that 60 percent of adolescents are looking at their phones in the last hour before sleep, and that they get on average an hour less sleep than their peers who don’t use their phones before bed. Blue light from electronic screens interferes with falling asleep; on top of that, checking social media is not necessarily a relaxing or sleep-inducing activity. Scrolling on social media, notes Dr. Hamlet, can easily end up causing stress. “Social media can have a profound effect on sleep,” adds Dr. Bubrick. “You have the intention to check Instagram or watch TikTok videos for 5 minutes, and the next thing you know 50 minutes are gone. You’re an hour behind in sleep, and more tired the next day. You find it harder to focus. You’re off your game, and it spirals from there.” How to minimize negative effects of social media use While we don’t yet have conclusive evidence that social media use actually causes depression, we do have plenty of warning signs that it may be affecting our kids negatively. So it’s smart for parents to check in regularly with kids about their social media use, to make sure it’s positive and healthy, and guide them towards ways to change it, if you think it’s not. Also, be alert for symptoms of depression. If you notice signs that your child might be depressed, take them seriously. Ask your child how they are doing, and don’t hesitate to set up an appointment with a mental health provider. Steps you can take to ensure healthy social media use: Focus on balance: Make sure your kids are also engaging in social interaction offline, and have time for activities that help build identity and self-confidence. Turn off notifications: App developers are getting more and more aggressive with notifications to lure users to interrupt whatever they’re doing to engage constantly with their phones. Don’t let them. Look out for girls at higher risk of depression: Monitor girls who are going through a particularly tough time or are under unusual stress. Negative effects of social media can have more impact when confidence is down. Teach mindful use of social media: Encourage teenagers to be honest with themselves about how time spent on social media makes them feel, and disengage from interactions that increase stress or unhappiness. Model restraint and balance in your own media diet: Set an example by disengaging from media to spend quality family time together, including phone-free dinners and other activities. Kids may resist, but they’ll feel the benefits. Phone-free time before sleep: Enforce a policy of no smartphones in the bedroom after a specific time and overnight. Use an old-fashioned alarm clock to wake up. Frequently Asked Questions

Keypoint: On average, primary care providers diagnose ASD 1 year earlier than other health care providers. Although primary care providers (PCPs) diagnose children with autism spectrum disorder (ASD) 1 year earlier than psychiatrists and psychologists, the likelihood of a PCP diagnosing a child with ASD has decreased every year from 2004 to 2019, according to study findings published in Autism. Further research is needed to understand this discrepancy and improve efficient diagnoses among children with ASD. An early diagnosis of ASD can be essential for initiating treatment during critical periods of development. Early interventions often lead to better long-term outcomes by addressing core challenges in childhood and connecting patients to necessary supports that improve their quality of life. A significant factor in achieving an earlier diagnosis is primary care appointment attendance, as PCPs are in a unique position to consistently monitor a patient’s development from infancy to childhood. Yet, the diagnostic tools required for an ASD diagnosis require extensive training and are often only used in specialized treatment centers. To determine whether PCP diagnoses of ASD have changed over time, investigators conducted a secondary analysis of data from the National Survey of Children’s Health (NSCH), a caregiver-report survey of the health and well-being of United States children from birth to 17 years of age. The goal of the analysis was to determine the rate of PCPs diagnosing ASD over time and children’s ages at diagnosis. Caregivers reported if a health care professional had ever diagnosed their child with ASD and were then asked to retroactively report which type of provider was the first to diagnose their child with ASD. The investigators collapsed the responses of provider type into PCP and non-PCP. A total of 5296 caregiver-reported diagnoses of ASD were included in the current study. On average, children were 5.13 (SD, 3.32) years of age at diagnosis, 76.8% of participants were White, 87.3% were non-Hispanic/Latinx, 80.0% of the children were boys, and 14.3% of the study group were first diagnosed with ASD by their PCP. From 2004 to 2019, the investigators found the likelihood of a PCP diagnosing a child with autism decreased by about 2% every year (odds ratio [OR], 0.98; 95% CI, 0.96-1.00). In a binary logistic regression model that controlled for demographic characteristics, the year in which a child was diagnosed with ASD was a significant, negative predictor of being diagnosed by a PCP (β, –0.02; P =.02). On average, children diagnosed with ASD by their PCP were about 1 year younger (4.10 years; SD, 2.67) than children diagnosed by a non-PCP (5.30 years; SD, 3.38; P <.001). The investigators wrote, “The present findings support the role PCPs play in early access to diagnosis, as age at first diagnosis of [ASD] was approximately [1] year earlier among children whose [ASD] was first diagnosed by their PCP as compared with non-PCPs.” Study authors concluded, “Overall, the current results indicate that more widespread access to diagnosis in primary care settings may have the potential to greatly reduce diagnostic delays in the years to come.” These study findings may be limited, as the investigators did not account for changes in ASD diagnostic criteria over the study period. Additionally, there was a lack of specificity in the survey questions and an inability to account for potential covariates (ie, living in an urban vs rural area, insurance type, and diagnostic features). Note: This article originally appeared on Psychiatry Advisor

The US Food and Drug Administration (FDA) has cleared Rejoyn (CT-152), the first prescription digital therapeutic authorized for the treatment of major depressive disorder (MDD) symptoms as an adjunct to clinician-managed outpatient care for adult patients with MDD aged 22 years and older who are on antidepressant medication. Rejoyn is a medical device with a novel approach to management of symptoms of depression. Rejoyn offers a 6-week treatment program with clinically-proven cognitive emotional training exercises for the brain, along with short therapeutic lessons. It is theorized to target the neural networks affected by depression and potentially use the brain’s inherent neuroplasticity to alter emotional connections, thus leading to a reduction in symptoms over time. “Rejoyn represents a novel and exciting adjunctive treatment option to address MDD symptoms that complements the current standard of care,” said John Kraus, MD, PhD, executive vice president and chief medical officer at Otsuka. “While traditional approaches are often effective, many are left with only a partial response to treatment. Otsuka has a long, unwavering commitment to addressing the unmet needs of people living with mental illnesses and the clearance of Rejoyn is an example of delivering on that promise. We are deeply grateful to the trial participants, clinicians, and everyone at Otsuka and Click Therapeutics, who helped Rejoyn reach this important milestone.” This clearance is based on data from a 13-week pivotal, multicenter, remote, double-blinded, randomized, controlled trial of 386 participants aged 22 to 64 who were diagnosed with MDD and on antidepressants. Participants were randomized to receive either Rejoyn or a sham control app. Those treated with Rejoyn showed an improvement in depression symptom severity from baseline and symptom improvement was consistently observed across multiple patient and clinician-reported scales, including the Montgomery-Åsberg Depression Rating Scale (MADRS), Patient Health Questionnaire 9-item depression scale (PHQ-9), and the Clinical Global Impression – Severity scale (CGI-S). Participants in the Rejoyn arm showed continued improvement 1 month after completing the 6-week treatment program. No adverse effects from Rejoyn were observed during the trial. “Only a third of patients diagnosed with depression and who receive antidepressants as their first-line treatment, are successful. These patients need new options that capitalize on proven-effective treatment strategies,” said David Benshoof Klein, cofounder and chief executive officer at Click Therapeutics. “The clearance of Rejoyn signals a fundamental change in how clinicians can treat symptoms of major depressive disorder. It provides hope for those who are looking for new treatment options, especially one that is easily accessible through the device in the palm of your hand.” Rejoyn introduces Emotional Faces Memory Task (EFMT) exercises2—designed to help participants appropriately process emotions—that were created by a team of psychologists, psychiatrists, and neuroscientists. The coinventor of EFMT, assistant professor in the department of psychiatry at the Icahn School of Medicine at Mount Sinai, and scientific advisor at Click Therapeutics, Brian Iacoviello, PhD, had this to say on the new digital therapeutic: “Rejoyn has a neuromodulatory mechanism designed to act like physical therapy for the brain by delivering personalized, consistent brain-training exercises designed to help improve connections in the brain regions affected by depression. When stronger and more balanced connections are created, the regions of the brain responsible for processing and regulating emotions are better able to work together and symptoms of depression can improve.” Rejoyn is expected to be available for download from app stores for iOS and Android operating systems later in 2024. This article originally appeared on Psychiatric Times

PSYCHIATRIC VIEWS ON THE DAILY NEWS Today is E-Day, Eclipse Day, an event of historical lore and meaning over millennia. Though many hope to see the total eclipse of the sun by the moon, certain expectations may be dashed with cloudy weather that obscures and eclipses what we see. Religious One set of reactions and meanings are religious and generally developed before current scientific information, such as the following: Christianity: There are some who believe this eclipse heralds the second coming of Christ and the “end times,” when Jesus will return to Earth, when the wicked will be judged and the righteous rewarded. Islam: It is generally felt to be a time to turn to God and pray, confirming that the occurrences of the whole universe are in God’s hands. Judaism: In the Talmud from hundreds of years ago, a total eclipse is “an ill omen for the world,” with the Orthodox recommending prayer, introspection, and a desire to do better. Hinduism. There are legends that incorporate the eclipse, which is generally viewed as a bad omen, so praying, meditating, and chanting are recommended to ward off evil. Buddhism: Buddhism can be put under the spiritual rubric perhaps more than religious given the absence of a God figure and views it as an auspicious day for spiritual practices like chanting mantras. Psychology Before scientific understanding, the eclipse seemed to elicit a primal fear, followed by relief, awe, and euphoria when the sun returned.2 People seem to care and cooperate more in its wake. Some, though, become obsessed with such solar eclipses, doing everything possible to see them. Social Being part of it tends to elicit a collective sense of wonder, inspiration, and reconciliation. A study after the last total eclipse in the US in 2017 found that individuals became, at least for a time, more oriented to their collectives.3 There is an accompanying sociological term called “collective effervescence.” Folk Beliefs Outside of formal religious beliefs, some common folk beliefs emerged in history. One is that a total eclipse is a disruption of the natural order and thereby a bad omen. Another is the common idea and image of the sun being eaten, such as by dragons, wolves, or demons. Human sacrifice could be a form of expiation, but alternatively, as with the Tlingit tribes, that the sun and moon were having more children. With a nod toward modern psychology, there is the interpretation of solar fighting with the moon, with the evolving expectation that everything would be worked out, just what we need for current polarizing times. Some have noticed how the pathway of this eclipse as well as the one in 2017, crosses in Carbondale, Illinois. Not only does that evoke Christ, but the famous legend about the blues great from the 1930s, Robert Johnson. At a crossroad in Clarksdale, Mississippi, in a combination of religious, folk, and sociological beliefs, it is said that he made a deal with the devil to obtain his great skill, then was poisoned by a jealous woman after a short, but great, career. The United States Today Coming into the midst of such a unique event makes analyzing it difficult. Certainly, there is much interest and plans to try to see the totality for the last time in 20 more years, even if by now the cloud cover is a concern. Many areas in the totality will have business benefits, including alcohol sales (which may boom if there is disappointment). Perhaps the biggest controversy and divisiveness now has been what to do with going to school—or not—for kids, sort of a mini version of what to do during COVID-19. While I have not found any major survey, many schools, with parental support, are operating from “an abundance of safety” and closing down for parts of today, providing e-classes at best. That leaves the parents to handle the watching process. Sometimes this is called an era of “safetyism” and helicopter parenting, too much of a good safety and security thing, but that also prevents necessary book and practical living learning. Perhaps we will get a better perspective on this strategy after the eclipse. Concluding Thoughts In general, most who view a total solar eclipse live are left with a sense of awe, though for how long is unclear. We also do not know much about the potential disappointment of not seeing it due to cloud cover, paralleling so many dashed expectations in life. The hoped for collective effervescence can certainly fizzle out. Perhaps the Robert Johnson legend reminds us of moral priorities. Conspiracy theories, which are common for this eclipse, evoke such moral questioning. Keeping any sense of spiritual awe alive is important for eclipses and other similar events. That can be done by deliberate memory recalls and searching for awe-inspiring events. The benefits of awe are both positive for mental and physical health. This article originally appeared on Psychiatric Times

Keypoint: Cancer survival rates are worse in adults with female breast, colorectal, or lung cancer who also have an intellectual or developmental disability. Patients with vs patients without intellectual or developmental disabilities have worse cancer survival rates, according to study findings published in the Canadian Journal of Public Health. Researchers conducted a population-based retrospective cohort study to explore the association between intellectual and developmental disabilities and cancer survival in adults with female breast, colorectal (CRC), or lung cancer. Outcomes of interest included death attributable to any cause and death attributable to cancer. Statistical analyses included Cox proportional hazards models and competing events analyses. The researchers sourced data from multiple linked databases in Ontario, Canada. Adult patients diagnosed with malignant breast (n=123,695), colorectal (n=98,809), or lung (n=116,232) cancer between 2007 and 2019 were evaluated for mortality on the basis of intellectual and developmental disability status. Requirements for intellectual and developmental disability status included the individual to have at least: 1 hospital admission, 1 complex continuing care admission, 1 emergency department visit, 1 home care visit, or 2 physician visits with an eligible diagnoses code in addition to a health encounter before cancer diagnosis. Overall, 486 (0.39%) patients with breast cancer (28.4% aged 50-59; 100% women), 506 (0.51%) patients with CRC (24.1% aged 60-69; 56.3% men), and 385 (0.33%) patients with lung cancer (30.4% aged 60-69; 54.0% men) met the criteria for intellectual or developmental disability. Among all cohorts, survival differed significantly on the basis of intellectual or developmental disability (P <.001). Compared with the patients with breast cancer, CRC, and lung cancer without intellectual or developmental disabilities, patients with these disabilities had lower 5-year overall survival rates across all cohorts (breast cancer: 81.7% vs 61.5%; CRC: 56.6% vs 34.2%; lung cancer: 19.7% vs 11.9%). After adjusting for cofounders, intellectual or developmental disability was associated with worse overall survival among patients with breast cancer (adjusted hazard ratio [aHR], 2.74; 95% CI, 2.41-3.12; P <.001), CRC (aHR, 2.42; 95% CI, 2.18-2.68; P <.001), or lung cancer (aHR, 1.49; 95% CI, 1.34-1.66; P <.001). Similarly, intellectual or developmental disability was associated with worse cancer-specific survival among patients with breast cancer (aHR, 2.28; 95% CI, 1.86-2.78; P <.001), CRC (aHR, 2.57; 95% CI, 2.26-2.92; P <.001), or lung cancer (aHR, 1.38; 95% CI, 1.21-1.57; P <.001). After stratifying cancer-specific survival by patient characteristics, intellectual or developmental disability was determined to be a significant predictor for mortality among all subgroups with breast cancer except for those with tumor, node, metastasis (TNM) stage 0 or I (aHR, 0.86; 95% CI, 0.32-2.30); among all subgroups with CRC; and among all subgroups with lung cancer except for those aged 49 and younger (aHR, 0.89; 95% CI, 0.48-1.66). Study limitations included documented prevalence of intellectual or developmental disabilities among patients with breast cancer, CRC, or lung cancer that were lower than estimated the prevalence of the same in Canada; potential misclassification of intellectual or developmental disability; the inability to differentiate types of intellectual or developmental disability; and loss to follow-up. “High-quality knowledge to inform patient-centered, evidence-based care gaps for people with IDD [intellectual or developmental disabilities] and cancer is urgently needed,” the researchers concluded. This article originally appeared on Neurology Advisor

Here’s some news you may have missed in the world of psychiatry from throughout the month of March, as featured in Psychiatric Times®. Phase 3 Trial of AXS-12 for Narcolepsy Meets Primary Endpoint The SYMPHONY phase 3 trial evaluating the efficacy of AXS-12 (reboxetine) for the treatment of narcolepsy has achieved positive results by meeting its primary endpoint. The trial revealed that AXS-12, a highly selective norepinephrine reuptake inhibitor and cortical dopamine modulator that was granted Orphan Drug Designation for the treatment of narcolepsy in 2018, successfully met its primary endpoint by significantly reducing the frequency of cataplexy attacks in patients with narcolepsy compared with placebo. “AXS-12 is a novel therapeutic approach to the treatment of narcolepsy as evidenced by the strong clinical results generated from the phase 3 SYMPHONY trial, including a rapid and significant reduction in cataplexy events compared to placebo,” said Michael Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center and professor of neurology at Albert Einstein College of Medicine, in a press release. Continue Reading Phase 3 Antipsychotic Candidate Pimavanserin Fails to Achieve Primary Efficacy Endpoint Recently released topline data from the phase 3 ADVANCE-2 trial reveals that the antipsychotic candidate pimavanserin did not achieve the primary efficacy endpoint of control of negative symptoms in patients with schizophrenia. Acadia Pharmaceuticals intends to discontinue research on pimavanserin for schizophrenia, following this failure. "Treatments to improve the negative symptoms in schizophrenia, a large unmet need, remain elusive," said John J. Miller, MD, Editor in Chief of Psychiatric Times. "Pimavanserin (Nuplazid), an inverse serotonin 2A receptor agonist, failed to separate from placebo in a Phase 3 double-blind study of 454 adults with schizophrenia treated for 26 weeks. We will await ongoing clinical trials with drugs of different mechanisms of action in our continued attempt to develop a treatment to improve negative symptoms." Continue Reading FDA Approves NeuroStar TMS for Treatment of MDD in Adolescents NeuroStar Advanced Therapy has received clearance from the US Food and Drug Administration (FDA) as an adjunct in the treatment of major depressive disorder (MDD) in adolescent patients aged 15 to 21 years. This clearance marks NeuroStar as the first and only transcranial magnetic stimulation (TMS) treatment that is FDA-cleared for this age group. MDD in adolescent patients is also the fourth FDA-cleared indication for NeuroStar, along with treatment of MDD in adults, treatment of obsessive-compulsive disorder in adults, and anxiety symptoms in adults with MDD. Continue Reading Note: This article originally appeared on Psychiatric Times

Studies in preclinical models hint that familial Alzheimer's disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans. The researchers observed that adoptive transplantation of donor bone marrow stem cells harboring a mutant human amyloid precursor protein (APP) transgene into both APP-deficient and healthy wild-type mice resulted in the rapid development of AD pathologic hallmarks. These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment. In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice. "Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients," the investigators, led by Wilfred Jefferies, BSc, DPhil, write. Although this is probably an "infrequent" occurrence, it's still "concerning," Jefferies told Medscape Medical News, and it suggests that "human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies." The study was published March 28 in Stem Cell Reports. Intriguing, but Limited Human Relevance The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD. Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC). David Curtis, MBBS, MD, PhD, with University College London's Genetics Institute, United Kingdom, noted that the study suggests that "theoretically there could be a risk of acquiring Alzheimer's disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells." Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is "scientifically intriguing" in demonstrating in this "very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited." Morgan cautioned against making the "gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer's disease and other neuropathologies in man." Bart De Strooper, MD, PhD, with University College London, agreed. "There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer's disease as a result of the procedure, and nobody should forgo a transplant for this reason," he said in the SMC release. The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures. Note: This article originally appeared on Medscape

Keypoint: These findings provide specific recommendations for the most efficacious psychotic depression treatment options. The combination of a selective serotonin reuptake inhibitor (SSRI) and a second-generation antipsychotic (SGA) may be the most effective psychotic depression treatment approach, according to results from a systematic review and meta-analysis published in Lancet Psychiatry. Psychotic depression, characterized by hallucinations or delusions occurring during a major depressive episode, is associated with greater symptom severity and duration than non-psychotic depression. While current psychotic depression treatment guidelines recommend polytherapy with an antidepressant and antipsychotic, there is limited research regarding the most efficacious options and combinations for specific medications. The current study aimed to address this research gap through a network meta-analysis to determine the efficacy of pharmacological treatments for psychotic depression, contributing to a more comprehensive understanding of treatment options. The investigators searched publication databases from inception to November 23, 2023 for randomized controlled trials evaluating the efficacy and safety of pharmacological treatments for acute major depressive episodes with psychotic features. The primary endpoints were treatment response rate and treatment acceptability, with secondary outcomes including changes in depressive symptom severity, remission rates, tolerability, and frequency of adverse events. The investigators included a total of 15 studies in the systematic review, for a pooled sample size of 1161 individuals with psychotic depression. On average, participants were 50.5 years of age, 44.4% were women, and 42.1% identified as White. The meta-analysis included 13 reports, encompassing 14 randomized controlled trials. Overall, 2 trials assessed depressive symptom severity using the Montgomery-Asberg Depression Rating Scale while the remaining studies used the Hamilton Rating Scale for depression. Relative to placebo, the investigators found that only the combination of SSRIs plus SGAs was associated with a higher proportion of participants with a treatment response (risk ratio [RR] 1.89; 95% CI, 1.17-3.04). By specific medications, only the combination of fluoxetine and olanzapine outperformed placebo (RR, 1.91; 95% CI, 1.27-2.85) for the proportion of patients with a treatment response. Additionally, the investigators found that antipsychotic plus antidepressant combinations were consistently more efficacious than monotherapy alone with either drug class. Among monotherapies, tricyclic antidepressants (TCAs) were associated with the most favorable response profile. These findings suggest that the combination of an SSRI plus an SGA may be the most optimal and effective treatment option for patients with psychotic depression. The study authors concluded, “This expansion of evidence for the pharmacological treatment of psychotic depression should improve clinical care, facilitate the development of treatment guidelines, and provide valuable insights for future clinical research, which remains insufficiently developed.” Limitations of the study include its reliance on data from randomized controlled trials published between 1985 and 2013, which excludes recent medications like ketamine or esketamine. Additionally, small sample sizes and the limited number of trials may affect the precision of effect estimates, while the inclusion of both major depressive disorder and bipolar disorder patients challenges the transitivity assumption and complicates the assessment of treatment effectiveness across the spectrum of psychotic depression. Note: This article originally appeared on Psychiatry Advisor

NeuroStar Advanced Therapy has received clearance from the US Food and Drug Administration (FDA) as an adjunct in the treatment of major depressive disorder (MDD) in adolescent patients aged 15 to 21 years. This clearance marks NeuroStar as the first and only transcranial magnetic stimulation (TMS) treatment that is FDA-cleared for this age group. MDD in adolescent patients is also the fourth FDA-cleared indication for NeuroStar,1 along with treatment of MDD in adults, treatment of obsessive-compulsive disorder in adults, and anxiety symptoms in adults with MDD. “The prevalence of depression in adolescents and young adults has been accelerating since the COVID-19 pandemic,” said Kenneth Pages, MD, medical director of TMS of South Tampa, in a press release. “The current treatment options available for adolescents are extremely limited, compared to those available for adults. NeuroStar’s TMS therapy now offers a promising first-line treatment for adolescents, backed by real-world data and impressive response rates consistent with response rates for adults. This advancement has the potential to set a new treatment paradigm for how we address depression in our youth.” The FDA’s decision to grant clearance for this indication is informed by an analysis of real-world data collected through NeuroStar’s proprietary TrakStar® platform. Among the 1169 adolescents analyzed, 78% showed clinically meaningful improvement in depression severity. The FDA reviewed this data set alongside clinical literature and concluded that NeuroStar TMS, when used as an adjunct to antidepressant therapy, is substantially equivalent in terms of safety and effectiveness compared to antidepressant therapy alone in this population. The coil design versatility of NeuroStar also allows providers to address the immediate treatment needs of adolescents with MDD symptoms without requiring additional hardware upgrades or purchases. This feature gives adolescent patients and their families a new option when weighing alternative treatments for depression. Access to effective treatment for MDD is important for all patient populations, as MDD is the fourth leading cause of disease burden globally. “Receiving FDA clearance to treat the adolescent segment aged 15 and up is a treatment solution that is long overdue in the mental health industry,” said Keith J. Sullivan, president and CEO of NeuroStar developer Neuronetics Inc, in a press release. “We are excited to offer NeuroStar TMS therapy as a new option for young people and for their concerned parents who have struggled to find a treatment they can be confident in. As a company, we will be focused on driving even more awareness and education about NeuroStar given that this new clearance grows our total advdnhfjshydfdressable market in MDD by 35%.” Note: This article originally appeared on Psychiatric Times

The size of the human brain has increased over time, a new finding that may help explain a previously reported decline in incident dementia. A secular trends analysis using brain imaging data from the long-running Framingham Heart Study, revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s vs those born in the 1930s. "We hypothesize that the increased size of the brain will lead to increased 'reserve' against the diseases of aging, consequently reducing overall risk of dementia," Charles DeCarli, MD, director of the Alzheimer's Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis, told Medscape Medical News. The study was published online on March 25, 2024, in JAMA Neurology. Dementia Protection? As previously reported by Medscape Medical News, an earlier paper from the Framingham Heart Study suggested dementia incidence is declining. "This difference occurred among persons with at least high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia," said DeCarli. The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930-1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI. Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2). Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area. "We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient," said DeCarli. Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings. "These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve," the authors wrote. While the effects observed are "likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheimer disease on dementia incidence," they added. Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference. Exciting Work "If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies," Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial. "First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with," Lemuria noted. "Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration," Vemuri added. The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Vemuri wrote. Although this work is "exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends," she added. "Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues," Vemuri concluded. Note: This article originally appeared on Medscape

Keypoint: There are significant racial disparities in the risk for psychotic continuum outcomes. The risk for schizophrenia, psychotic symptoms (PSs), and psychotic experiences (PEs) are higher among Black and Latinx patients compared with White patients, according to study results published in JAMA Psychiatry. Although previous research has indicated that Black individuals are at higher risk for psychotic disorder diagnoses, relatively little is known about how risk varies across ethnoracial groups for other psychosis continuum outcomes — namely PSs, PEs, and clinical high risk for psychotic disorder [CHR-P]). To this aim, investigators conducted a systematic review and meta-analysis to assess the risk variation for these psychosis continuum outcomes across multiple racial and ethnic groups. The investigators searched publication databases from inception to December 2022 for observational studies conducted in the United States that evaluated psychotic disorder diagnoses, CHR-P, or PSs/PEs as outcomes among at least 2 ethnoracial groups. The primary outcome of the meta-analysis was schizophrenia spectrum diagnoses, while secondary analyses evaluated the risk for CHR-P and PSs/PEs. Overall, a total of 47 studies were included in the meta-analysis for a pooled total of 54,929 patients with schizophrenia (Asian: 4653; Black: 15,146; Latinx: 14,516; White: 19,744; Other: 870) and 223,097 patients with PSs/PEs (Asian: 16,951; Black: 25,528; Latinx: 17,683; White: 156,627; Other: 6308). Of the included studies, 32 evaluated a psychotic disorder, 29 assessed PSs/PEs, and 3 investigated CHR-P. Relative to White individuals, the investigators observed higher odds of a schizophrenia spectrum diagnosis among Black patients (odds ratio [OR], 2.07; 95% CI, 1.64-2.61; P <.01) and individuals who identified as Other (OR, 1.81; 95% CI, 1.31-2.50; P <.01). The investigators also found that the risk for PSs/PEs was higher among Black (pooled standardized mean difference [SMD]; 0.10; 95% CI, 0.03-0.16) and Latinx individuals (pooled SMD, 0.15; 95% CI, 0.08- 0.22) compared with White participants. The investigators also conducted sensitivity analyses based on treatment setting, diagnosis, and sampling characteristics. When compared with White individuals, the investigators found that Asian individuals displayed greater odds of a schizophrenia spectrum diagnosis when treated in inpatient settings (OR, 1.84; 95% CI, 1.19-2.84; P <.05) and when participants were sampled in a college setting (Cohen d, 0.16; 95% CI, 0.02-0.29; P <.05). The investigators did note a high level of heterogeneity across the included studies. Researchers concluded, “Ethnoracial risk variation in the US is present across multiple psychosis-related outcomes, suggesting that factors other than diagnostic bias alone underlie these disparities.” These results may be limited, given the risk for bias due to the included studies’ insufficient controlling of confound variables, the low representativeness of sample populations, high heterogeneity, and poorly assessed and defined ethnoracial groups. Note: This article originally appeared on Psychiatry Advisor

Executive dysfunction among young people with autism spectrum disorder (ASD), aged 16 to 21 years, is a significant indicator of suicide risk, according to study findings published in Autism. Previous research has established that individuals with ASD are at higher risk for suicide relative to neurotypical individuals. While issues with executive function have been associated with suicide risk in other populations, it has been an underexamined factor among people with ASD — particularly younger individuals. To this aim, investigators evaluated the suicide risk for individuals with ASD, aged 16 to 21 years, and examined depression, autistic traits, and executive function as potential predictors. The investigators conducted a cross-sectional study using data from the TEACCH School Transition to Employment and Post-Secondary Education (T-STEP) program, a community college-based intervention. At intake, demographic information was collected and participants completed the Wechsler Abbreviated Scales of Intelligence-II (WASI-II), P4 Suicide Screener, Behavior Rating Inventory of Executive Functioning — Adult Version (BRIEF-A), Center for Epidemiological Studies — Depression, Revised (CESDR), and Social Responsiveness Scale, 2nd Edition (SRS-2). A total of 183 individuals with a medically confirmed diagnosis of ASD were included for analysis. On average, participants were 18.75 (SD, 1.40) years of age, 73.2% were boys/men, and 74.9% identified as White. These findings highlight the need for integrated intervention approaches between both mental health and developmental disability service systems in order to target complex treatment needs. The investigators found that 33.3% (n=61) of individuals with ASD had experienced suicidal ideation in their lifetime. Among the group with ideation, 34% reported prior suicide attempt(s), 43% made a suicide plan, and 10% reported an intent to act on thoughts of self-harm within the next 30 days. The investigators then categorized subjects into risk categories based on their responses. Of the total sample, 65.6% of respondents were “no risk”, 16.4% reported ideation with no additional risk factors and were categorized as “minimal risk”, 14.2% reported ideation and 1 additional risk factor and were categorized as having lower risk, and 3.8% of participants who reported ideation and had multiple additional risk factors and were categorized as “higher risk”. The investigators found that higher levels of executive dysfunction were correlated with higher autistic traits (r, 0.49; P <.01), increased depression (r, 0.15; P <.05), and suicidal risk (r, 0.22; P <.01). Conversely, autistic traits were not significantly associated with overall suicide risk. In evaluating predictors of suicide risk, the investigators conducted regression analysis and found that executive dysfunction uniquely predicted suicidality (χ2, 30.36; P <.001), even when controlling for depression (b, 0.02; SE, 0.01; P <.05). The model that included executive dysfunction accounted for approximately 16% of the variance in reported suicidal ideation (R2, 0.16). Note: This article originally appeared on Psychiatry Advisor