Dimensional phenotype measurement in children with rare genetic conditions: new insights into the aetiology of neurodevelopmental and psychiatric disorders

Rare neurodevelopmental genetic conditions (NGCs) present with diverse and complex phenotypic manifestations, often resulting in a range of clinical and cognitive difficulties that cut across traditional, categorically defined neurodevelopmental and neuropsychiatric diagnoses. Traditional categorical diagnostic frameworks have significant limitations in capturing the full complexity and heterogeneity of these phenotypes. This perspective reviews current advances in the field, highlighting the benefits of dimensional frameworks like the Research Domain Criteria (RDoC) and the Hierarchical Taxonomy of Psychopathology (HiTOP). Dimensional approaches have shown promise in capturing subthreshold symptoms and behavioural dimensions predictive of later neuropsychiatric outcomes. The transition to dimensional frameworks offers significant potential for improving diagnostic accuracy and informing personalised treatment strategies. However, the field remains hindered by the lack of standardised and validated dimensional assessment tools. Future research should focus on developing new assessment tools that are specifically designed for NGCs and are culturally and neurodivergence sensitive, with researchers, clinicians, and families codeveloping measures to ensure the practical application of these tools.
<![CDATA[New youth-focused substance use guidelines spotlight prevention, brain development, and coordinated mental health support to improve outcomes early.]]>

STAT+: Access granted: CMS greenlights more than 150 participants for chronic care experiment

More than 150 companies and providers have been provisionally approved to participate in an experimental Medicare program meant to expand access to technology-supported chronic care. They include popular mental health apps, wearable device makers, a life sciences company tied to Google, and startups that help large health systems manage heart failure patients.

Announced late last year by the Center for Medicare and Medicaid Innovation, the ACCESS model will pay participants set rates to treat chronic conditions like diabetes, hypertension, high cholesterol, musculoskeletal pain, anxiety, and depression. The payments are tied to measurable health outcomes; the model is meant as an alternative to paying for individual technology services. The initial deadline to participate in the first ACCESS cohort was April 1, but CMMI Monday announced it will extend the deadline to allow more to join.

CMS officials say the large number of applications to participate in ACCESS exceeded their expectations and that the enthusiasm suggests modest payment rates and restrictions did not discourage digital health companies from applying. According to officials, most of the participants had not previously served Medicare patients. 

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Designing Psychologically Grounded Artificial Intelligence for Supporting Bystander-Based Cyberaggression Intervention: Mixed Methods Exploratory Study

Background: Cyberaggression poses a growing threat to mental health, contributing to increased distress, reduced self-esteem, and other adverse psychosocial outcomes. Although bystander intervention can mitigate the escalation and impact of cyberaggression, individuals often lack the confidence, strategies, or language to respond effectively in these high-stakes online interactions. Advances in generative artificial intelligence (AI) present a novel opportunity to facilitate digital behavior change by assisting bystanders with contextually appropriate, theory-informed intervention messages that promote safer online environments and support mental well-being. Objective: This mixed methods design study aimed to explore the feasibility of using generative AI to support bystander intervention in cyberaggression on social media. Specifically, we examined whether AI can generate effective responses aligned with established intervention strategies and how these responses are perceived in terms of their potential to de-escalate online harm and foster behavior change. Methods: We collected 1000 real-world cyberaggression examples from public social media datasets and generated bystander intervention responses using 3 distinct prompt strategies: a generic policy reminder, a baseline GPT prompt, and a theory-driven GPT prompt (AllyGPT). To evaluate the responses, we conducted computational linguistic analyses to assess their psycholinguistic features and carried out a mixed methods evaluation. Three trained coders rated each message on favorability, conversational impact, and potential to change behavior and later participated in semistructured interviews to reflect on their evaluation process and perceptions of intervention effectiveness. Results: Linguistic analyses revealed that baseline GPT responses exhibited more emotionally positive and authentic language compared to AllyGPT responses, which showed a more analytical and assertive tone. Policy reminder messages were linguistically rigid and lacked emotional nuance. Human evaluation results showed that AllyGPT responses received the highest effectiveness ratings for low-incivil cyberaggression cases in 2 dimensions (favorability and changing behavior), and baseline GPT works better for mid and high levels for all effectiveness dimensions. For medium- and high-incivility aggressions, baseline GPT responses received the highest ratings across all 3 dimensions of effectiveness (favorability, discussion-shifting potential, and likelihood of changing bullying behavior), followed by AllyGPT, with policy reminders rated lowest. Qualitative feedback further emphasized that baseline GPT responses were perceived as natural and inclusive, while AllyGPT responses, although grounded in psychological theory, were sometimes viewed as overly direct. Policy reminders were considered clear but lacked persuasive impact. Conclusions: Our work showed that designing effective AI-generated bystander interventions requires a deep sensitivity to platform culture, social context, and user expectations. By combining psychological theory with adaptive, conversational design and ongoing feedback loops, future systems can better support bystanders, delivering interventions that are not only contextually appropriate but also socially resonant and behaviorally impactful. As such, this work serves as a foundation for scalable, human-centered AI systems that promote safer online spaces and users’ mental well-being.
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Co-Design of a Depression Self-Management Tool for Adolescent and Young Adult Cancer Survivors: Rapid Qualitative Analysis of Interview Feedback on a Prototype

<strong>Background:</strong> Over 2.1 million adolescent and young adult cancer survivors (AYACS) live in the United States. Recent estimates suggest that up to one-third of AYACS experience major depressive disorder. Although several efficacious evidence-based interventions are available to manage symptoms of depression, these interventions are often inaccessible to AYACS who have many competing commitments. Digital mental health tools hold promise for this population; however, only a few have been tailored to meet the unique needs of AYACS, and findings to date have yielded mixed results. <strong>Objective:</strong> This study aims to obtain feedback from AYACS on a mid-fidelity prototype of a depression self-management tool being tailored for AYACS. <strong>Methods:</strong> Individuals with a history of cancer diagnosed at age 12 or older who were between the ages of 15 and 39 and had completed primary treatment were identified through a review of medical records from a comprehensive cancer center in the Southeastern United States. Potentially eligible participants were contacted by study staff to conduct additional screening and obtain informed consent via REDCap (Research Electronic Data Capture; Vanderbilt University). Upon enrollment, participants provided demographic and clinical information, as well as their availability for an interview. The principal investigator (KMI) conducted semistructured individual interviews with consented AYACS. Most of the interview was dedicated to showing participants the mid-fidelity prototype of the tool, explaining how the prototype might work, and requesting targeted feedback. Demographic and clinical characteristics, as well as some aspects of feedback on the prototype, were summarized using descriptive statistics. Interviews were audio- and video-recorded and transcribed. The transcriptions underwent rapid qualitative analysis guided by the Rigorous and Accelerated Data Reduction technique. <strong>Results:</strong> A total of 14 AYACS (n=9, 64%, female; n=9, 64%, white; ages 15-38) completed an individual interview. Participant preferences for mood tracking, content presentation, user input, and duration of use were captured qualitatively but analyzed quantitatively. For example, most participants (n=10, 71%) indicated that they preferred a mood-tracking option that included emojis and would be willing to track their mood at least once per day (n=11, 79%). Participant preferences captured qualitatively fell into 4 themes: (1) features to promote user engagement (eg, the use of gamification); (2) tailored content presentation (eg, authenticity in the portrayal of the cancer experience); (3) perceived usability (eg, simplifying user input); and (4) interface design (eg, implementing a coherent design theme and color scheme). <strong>Conclusions:</strong> Findings indicated that AYACS highly value personalization, flexibility, and peer support in digital interventions. Based on insights obtained during individual interviews, a working prototype was developed by reprogramming an existing digital tool. Qualitative and quantitative findings informed modifications to the existing digital tool. The working prototype will next undergo evaluation as part of a pilot full-factorial trial.

Evaluation of anxiety levels and stress coping methods of pregnant women after the Kahramanmaraş earthquake

ObjectiveNatural disasters can cause serious psychological pressures on women during pregnancy. How the mental health of pregnant women is affected after major disasters such as earthquakes and what coping methods come into play in this process is an important research topic. This study aimed to evaluate the anxiety levels and stress coping strategies of pregnant women who experienced the February 6, 2023 Kahramanmaraş earthquake.MethodsThis cross-sectional descriptive study was carried out within four months after the earthquake. A total of 118 pregnant women were included. Participants were grouped according to pregnancy trimester. Anxiety level was assessed with the Beck Anxiety Inventory and coping strategies with the Brief COPE Scale. Earthquake exposure data, including building damage and loss of relatives, were collected via structured survey.ResultsThe mean Beck Anxiety score was 15.9 ± 12.8. A significant difference was observed between trimesters (H = 19.09, p < 0.001), with anxiety declining from the first to the third trimester. Religious coping (ρ = 0.42, p < 0.001), acceptance (ρ = 0.36, p < 0.001), and behavioral avoidance (ρ = 0.36, p < 0.001) were positively correlated with anxiety. Positive reinterpretation and development showed a significant negative correlation with anxiety (ρ = −0.32, p < 0.001). Building damage category was not significantly associated with anxiety (p = 0.80).ConclusionAnxiety in post-earthquake pregnant women differs according to trimester, and individual coping styles are associated with anxiety levels. Within the scope of the variables measured in this study, positive reinterpretation showed the strongest negative association with anxiety. Approaches supporting cognitive flexibility should be prioritized in perinatal mental health interventions.

Epigenetics at Birth Links Microbiome to Neurodevelopment, Potentially ASD and ADHD

The results of a study headed by researchers at Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, indicate that the gut microbiome and epigenetics are intertwined, and that both contribute to neurodevelopment.

The researchers showed that epigenetic changes present at birth can impact how an infant’s gut microbiome develops during their first year. They also identified specific epigenetic changes and gut microbes that were associated with signs of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) when the children were three years old.

“Certain bacteria seem to offer protection, which is exciting because it suggests there could be ways to support a child’s development through diet or probiotics in the future,” said research lead and gastroenterologist Francis Ka Leung Chan, MD. Chan is co-senior author of the team’s published paper in Cell Press Blue, titled “Epigenome-microbiome interplay in early life associates with infants’ neurodevelopmental outcomes,” in which they stated, “We showed that epigenetic alterations at birth were associated with early-life microbiome development and that they determine the risks of neurodevelopmental consequences in children.”

The first years of life are critical for brain development and immune system maturation. Though previous studies have shown that both early epigenetic changes and gut microbiome development can impact health in later life, little is known about how these two systems interact. “Recent data suggest that epigenetic programming of gene expression profiles is sensitive to the early-life environment and can impact health outcomes in children,” the authors wrote. “One environmental cue known to trigger host epigenetic modifications is the genes of bacteria, fungi, and viruses inside the human body, collectively known as the microbiome.”

Co-senior author and public health researcher Hein Min Tun, PhD, of The Chinese University of Hong Kong, commented, “We wanted to see how the epigenome and microbiome interact in early life and if their interaction could influence a child’s risk of developing neurodevelopmental conditions like ASD and ADHD.” The authors added, “New understanding of host-microbe-epigenome interactions and mechanisms of epigenetic changes in early life can be leveraged for the prevention, early detection, and novel interventions of common childhood diseases.”

For their study the researchers characterized DNA methylation patterns from the umbilical cord blood of 571 infants. They paired this information with gut microbiome data collected from 969 infants at two, six, and 12 months of age, and from their parents during the third trimester of pregnancy. When the children reached 36 months of age, the researchers used a behavioral questionnaire to assess their neurodevelopment and investigate links between the microbiome, epigenome, and early signs of ASD and ADHD.

“This, to our knowledge, represents the first longitudinal study with multiple sample types to depict the intimate interplay between perinatal exposures, epigenetic hallmarks, and gut microbiome development and neurodevelopmental outcomes within the first three years of life,” the authors stated.

They found that an infant’s epigenome at birth was associated with birth mode, length of gestation, having older siblings, and maternal allergies, but it was not affected by their parents’ gut microbiomes. Microbiome development, on the other hand, was associated with birth mode, antibiotics, having older siblings, and breastfeeding. Infants who were born by Caesarean section (CS) showed different patterns of DNA methylation for several genes involved in immune responses and brain development. “Some of the changes in methylations of immune- and nervous-system-related genes, associated with CS delivery, are linked to neurodevelopmental outcomes,” they noted.

Their reported findings, the team suggested, “… resonate with studies linking CS to increased risks of immune-mediated and neurodevelopmental disorders, providing mechanistic plausibility through epigenomic and microbial dysbiosis.” The team also showed that an infant’s epigenome at birth impacted how their microbiome developed during their first year. Specifically, infants developed less diverse gut microbiomes at 12 months of age when they showed higher rates of DNA methylation in immune genes involved in recognizing pathogens. “We found that methylation rates in the major histocompatibility complex (MHC) region of infants at birth were linked to differences in the diversity of the infant gut microbiome at 12 months,” they commented.

The behavioral survey revealed that signs of ASD and ADHD in three-year-olds were associated with specific epigenetic patterns and the presence of certain gut microbes. “Importantly, we reported that epigenetic modifications were associated with an increased susceptibility to neurodevelopmental conditions in children, and these effects were in part mediated by microbial colonization.”

However, other microbial species seemed to mitigate these effects: infants with epigenetic patterns associated with ASD or ADHD were less likely to show signs of the disorders if they acquired Lachnospira pectinoschiza and Parabacteroides distasonis, respectively, during their first year. “We discovered a kind of conversation happening: a baby’s epigenetic setting at birth can influence their risk for neurodevelopmental disorders, but the presence of certain ‘good’ bacteria in their gut can step in and modify the risk,” Tun reported. “The foundations for brain health are laid very early, even before birth. However, we don’t want people to think this means a child’s developmental path is fixed at birth. These are complex conditions with many causes, and we’ve only uncovered a small piece of a very large puzzle.”

The researchers are continuing to follow the children who participated in the study to see how these early-life factors relate to their health as they grow. They note that laboratory experiments are needed to confirm the associations between gut microbes and neurodevelopment. In their discussion, the team wrote, “In conclusion, our findings revealed dual alterations to the neonatal epigenome and gut microbiome by perinatal factors and highlight the role of the ‘holo-epigenome’—the integrated host epigenome and microbiome—as a key mediator of neuro-immune outcomes. Interventions targeting microbial restoration or epigenetic modulation during critical developmental windows may mitigate risks of neurodevelopmental disorders.”

First author and gastroenterologist Siew Chien Ng, MD, PhD, added, “The ultimate goal is to develop safe, non-intrusive early interventions such as specific probiotics or live biotherapeutics, that could help nurture a healthy gut microbiome and potentially reduce the risk of neurodevelopmental challenges.”

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Nonlinear relationships between fatigue, fear of COVID-19, and PTSD among mental health professionals: the findings of a multi-site survey in China

BackgroundMental health professionals (MHPs) are susceptible to fatigue, particularly during public health crises like the COVID-19 pandemic. This study examined nonlinear relationships between fatigue, post-traumatic stress disorder (PTSD), and fear of COVID-19 (FOC) among MHPs.MethodsA multi-site survey was conducted from January to February 2023. Fatigue was assessed using the Fatigue Visual Analogue Scale (VAS), PTSD with the Post-Traumatic Stress Disorder Checklist for Civilians (PCL-C), and FOC with the Fear of COVID-19 Scale (FCV-19S). Data were analyzed using logistic regression and restricted cubic splines to explore non-linear associations.ResultsOf the 9,858 COVID-recovered MHPs, the prevalence of significant PTSD symptoms (PCL-17 ≥ 50) was 6.85% (95% CI: 6.35% – 7.35%), while significant fear of COVID-19 (FOC ≥ 16) was observed in 61.28% (95% CI: 60.32% – 62.24%). Higher fatigue levels were significantly associated with increased odds for exacerbated PTSD symptomatology (OR = 1.75, 95% CI: 1.65 – 1.86, p < 0.001) and FOC severity (OR = 1.19, 95% CI: 1.16 – 1.21, p < 0.001). Restricted cubic splines analysis revealed nonlinear relationships. Specifically, as fatigue rose towards an inflection point of 5.00, its association with PTSD symptoms strengthened, while its association with FOC showed a decelerating growth.ConclusionThis study underscored fatigue as a factor significantly associated with COVID-recovered MHPs, particularly regarding the presence of PTSD and FOC. However, due to the cross-sectional study design, the direction of causality between fatigue, PTSD, and FOC could not be determined. Regular monitoring and targeted interventions are crucial for managing fatigue during public health crises. Healthcare organizations should provide appropriate work-rest schedules and supportive policies during such periods.

How sports betting apps hook users

For most of the last 80 years, sports betting was limited to Las Vegas. But after a 2018 Supreme Court decision loosened regulations on professional sports wagers, it became possible to place bets on games 24/7 — with nothing more than a smartphone and a bank account. 

In 2013, just five years prior to the landmark SCOTUS case, gambling was classified in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in a new category called “Substance-Related and Addictive Disorders.” This grouped gambling with alcohol use disorder and other addictions. Gambling is also known to have the highest suicide rate of any addiction.

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Peer Mentor Training and Supervision for a Digital Adolescent Depression Treatment in South Africa and Uganda: Mixed Methods Evaluation

Background: Blended digital mental health interventions combining technology with human support are more effective than stand-alone treatments. However, limited research has examined how to train and supervise personnel delivering human support components. The Kuamsha app, a gamified digital intervention for adolescent depression based on behavioral activation, was designed to be paired with low-intensity telephone-based peer support. A structured training and supervision program for peer supporters was codeveloped through workshops with mental health professionals and youth with lived experience of mental health challenges in South Africa and Uganda. To the best of our knowledge, this is the first study to evaluate a structured peer mentor model within a digital mental health intervention in low- and middle-income countries. Objective: This study assessed the feasibility, acceptability, and fidelity of a training and supervision program for peer supporters delivering a digital mental health intervention in South Africa and Uganda. Methods: We conducted a mixed methods evaluation of the peer mentor program. Quantitative metrics assessed the feasibility of recruitment, retention, and attendance among peer mentors (n=13, South Africa; n=4, Uganda), as well as training acceptability. Fidelity, adherence, and competence were scored at the session level and converted to percentages of the maximum possible score. Linear mixed-effects regression models with a random intercept for provider and site estimated adjusted marginal means (95% CI). In-depth interviews and focus group discussions explored program acceptability and implementation factors. Results: The peer mentor training and supervision program was feasible and acceptable in both settings, with high recruitment (South Africa: n=13/19, 68%; Uganda: 4/4, 100%), retention (South Africa: 9/13, 69%; Uganda: 4/4, 100%), and training attendance rates (89%‐92% in South Africa and 100% in Uganda), alongside qualitative reports of high satisfaction. All peer mentors met a minimum posttraining competency threshold (≥50%), with median competency scores of 70.7% (IQR 45.8%‐78.2%) in South Africa and 75.4% (IQR 73.8%‐77.3%) in Uganda. Independent ratings of recorded calls indicated high overall fidelity in South Africa (84.7%, 95% CI 80.3%‐89.0%) and Uganda (87.7%, 95% CI 83.4%‐92.1%). Adherence was higher in Uganda than South Africa (adjusted mean difference [AMD] 13.30 percentage points, 95% CI 8.99‐17.61; <.001), as was competence (AMD 4.88 percentage points, 95% CI 1.23‐8.53; =.009). The AMD in overall fidelity (3.06 percentage points, 95% CI −0.98 to 7.10) was not statistically significant (=.14). The qualitative findings emphasized the value of ongoing supervision and capacity development, interactive training approaches, and blended delivery models. Conclusions: Locally adapted training and supervision models can strengthen peer mentor capabilities to support digital interventions. Adequate supervisory capacity and incentive structures are critical to sustain engagement, retention, and fidelity. In settings with frequent network disruptions, periodic in-person contact between peer mentors and supervisors may enhance fidelity. Future research should examine how peer mentor fidelity influences user engagement and mental health outcomes. Trial Registration: Pan African Clinical Trials Registry PACTR202206574814636; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23792 International Registered Report Identifier (IRRID): RR2-10.1136/bmjopen-2022-065977