Background: Depression is highly prevalent yet undertreated among people living with heart failure, indicating barriers to mental health services. Although various digital mental health interventions have been developed to detect, treat, and manage depression in this population, these interventions have seen limited integration into clinical care and a lack of implementation research. Stepped care is a service innovation that may promote the implementation of these technologies into clinical settings, but few studies have examined how these services are designed in clinical settings. Objective: This study aimed to identify strategies to address health system barriers to accessing mental health care from the perspective of people living with heart failure, clinicians, and researchers, and to incorporate these strategies into the design of a virtual mental health stepped care service within a heart failure remote management program. Methods: A qualitative description study was conducted using purposive recruitment of people living with heart failure, clinicians, and researchers from a heart failure remote patient management program. As part of a service design approach, semistructured interviews explored potential strategies to address barriers to accessing mental health services. Two researchers coded the data descriptively and constructed themes to guide the development of a virtual stepped care service. Results: A total of 22 participants were interviewed, comprising 13 people living with heart failure and 9 clinicians and researchers. Six themes were identified, comprising 4 requirements and 2 foundational principles. The requirements were to (1) adopt a collective approach to identify distress across methods, people, and time points; (2) maintain a referral-based approach; (3) rely on existing mental health human resources; and (4) offer patient choice among various mental health care options. These requirements were supported by two principles: (1) building on organizational strengths and (2) reducing treatment burden. Based on these findings, a virtual stepped care service was developed, incorporating a depression screening module, referral-based workflows, and, where clinically appropriate, patient choice in treatment selection. Conclusions: The stakeholder-informed design of this virtual stepped care service contributes to the limited literature on stepped care service design and demonstrates how such models can be tailored to their intended contexts. Although each component was designed to address health system barriers to mental health care for people living with heart failure, resource limitations may constrain the balance between feasibility and quality of care. Future research should evaluate the acceptability of this model among people living with heart failure and clinicians.
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Mitochondrial dysfunction, neuroinflammation, and associated mechanisms in sepsis-associated encephalopathy: from pathogenesis to emerging therapeutics
Sepsis-associated encephalopathy (SAE) is a devastating neurological complication of sepsis, leading to diffuse brain dysfunction, long-term cognitive deficits, and increased mortality. Its pathogenesis is complex, with mitochondrial dysfunction and neuroinflammation emerging as central, interconnected drivers. This review systematically elucidates the pathogenic crosstalk between these two processes. We detail how dysregulated mitochondrial dynamics (e.g., Drp1-mediated fission), impaired biogenesis (via the proliferator-activated receptor-gamma coactivator-1α axis), oxidative stress, and the activation of mitochondria-dependent cell death pathways (ferroptosis, pyroptosis) contribute to neuronal injury. Concurrently, microglial activation, particularly through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, creates a vicious cycle that exacerbates mitochondrial damage and synaptic loss. Furthermore, we summarize emerging therapeutic strategies that target this mitochondrial-neuroinflammatory axis, including molecular hydrogen, mitochondria-targeted peptides (SS-31), natural compounds, and specific inhibitors (e.g., Mdivi-1, MCC950). The integration of recent insights on the gut-brain axis and cerebral metabolomics further expands the therapeutic landscape. Ultimately, targeting this core axis offers a promising paradigm for developing effective interventions to improve neurological outcomes in septic patients.
A longitudinal analysis of the prevalence of restrictive interventions involving women with mental health conditions, learning disabilities or autism in mental health services in England
IntroductionRestrictive interventions, including physical restraint, seclusion, chemical restraint, and segregation, continue to be used within mental health services, despite sustained policy efforts to promote least-restrictive and trauma-informed care. However, little is known about national trends affecting women, for whom restrictive interventions often carry heightened risks of re-traumatisation and stigma.MethodsWe conducted a longitudinal secondary analysis of publicly available administrative data from the Mental Health Bulletin covering NHS-funded mental health services in England between 2017 and 2025. Annual counts of restrictive interventions involving women were examined relative to the number of women detained under the Mental Health Act to estimate annual rates per 1,000 detained. Regression modelling was used to assess temporal trends overall, by age group and type of restrictive intervention, and interrupted time-series analyses to examine changes following implementation of the Mental Health Units (Use of Force) Act 2018 (“Seni’s Law”). Trends were also examined alongside available national data on restrictive interventions involving men.ResultsRates of restrictive interventions involving women increased by approximately 12 percent per year over the study period, with no evidence of a reduction following the introduction of Seni’s Law. Increases were most pronounced for chemical restraint, seclusion, and segregation, while physical and mechanical restraint remained stable. Restrictive interventions declined among women under 18 but increased consistently across all adult age groups, indicating a widening age-related divergence. Although overall trends broadly mirrored those observed among men, the types of restrictive interventions used and their potential impact may differ, highlighting gendered dimensions in how restrictive practices are experienced and applied.DiscussionDespite extensive national initiatives, restrictive interventions involving women have continued to rise in England, highlighting a persistent gap between policy intent and practice. The findings suggest that legislative frameworks alone are insufficient to achieve meaningful reductions without operational changes in clinical practice, organisational culture, and monitoring systems. Internationally, the study contributes rare gender-disaggregated longitudinal evidence and highlights the need for comparable monitoring systems and coordinated research to inform rights-based, trauma-informed strategies to reduce restrictive interventions in mental health services.
Medical evaluation of first presentation of psychotic symptoms in children and adolescents
IntroductionPsychotic symptoms in children and adolescents may represent either normative developmental phenomena or severe psychiatric and medical conditions, requiring careful differential diagnosis.MethodsThis retrospective study aimed to evaluate the medical workup of children and adolescents admitted for a first presentation of psychotic symptoms at a tertiary pediatric center over a 10-year period. The sample included 68 patients (mean age 13.7 ± 3.7 years) who underwent clinician-directed evaluations including physical exams, laboratory tests, toxicology screens, neuroimaging, and lumbar puncture when indicated.ResultsSixteen patients (23.5%) were diagnosed with substance-/medication-induced or medically-associated psychosis. In this cohort, younger age, very early onset psychosis (<13 years), and catatonia at first presentation were more frequently observed among patients with secondary etiologies, whereas documented prior subthreshold symptoms were more frequently documented among those diagnosed with primary psychiatric disorders. Most investigations did not identify a secondary cause, reflecting clinician-directed evaluation in routine practice; however, selected cases (e.g., autoimmune encephalitis, multiple sclerosis) illustrate the clinical importance of careful assessment when specific suspicion is present.ConclusionThese findings suggest that targeted medical evaluation may be useful in pediatric psychosis, particularly when clinical features raise suspicion for secondary etiologies, and may help inform clinical decision-making in tertiary pediatric settings.
Self images: an empirical enquiry into Rembrandt’s self-portraits
Many have speculated that events of personal and financial loss in the life of Rembrandt van Rijn (Rembrandt) caused depression and that this is revealed by examination of his work particularly self-portraits painted in old age. Some report detecting various physiological diseases associated with aging, including vision impairment, which may have affected his mood and work. Aging and neurodegenerative disease which often accompanies it, are both associated with depression. Depression is characterised by visual deficits including perception of reduced contrast and colour. Age-related neurological disorders are associated in artists with reduced complexity. Recent advances in imaging and computer technology make it possible to empirically examine changes in artistic style which can contribute to understanding artists’ physical and mental health. Previous studies have identified associations between adverse events in artists’ lives and altered contrast and colour in their self-portraits. In the current study changes in contrast, colour and fractal dimension were measured in the entire corpus of Rembrandt’s painted self-portraits and portraits to determine whether changes in style indicate depression, cognitive decline, or neurological disease and whether differences in style can be detected between self-portraits and portraits of related and unrelated others. Productivity was also examined as an indirect indicator. The results suggest that it is unlikely that Rembrandt suffered from unipolar or bipolar depression, age-related cognitive decline, or neurodegenerative disease. The data are consistent with someone experiencing episodes of low mood associated with normal grieving and adversity followed by resilient recovery. There is evidence of a gradient in saliency and complexity between self-portraits and related and unrelated portraits and of a ‘late’ style identified by leading art historians consistent with macular degeneration.
Kent and Medway mental health appointments launch online
Kent and Medway Mental Health NHS Trust has a launched a portal to give patients 24/7 online access to their mental health appointments.
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.
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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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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