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May 7, 2026

Barriers and Facilitators in the Implementation of the Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health Digital Intervention in Rural India: Mixed Methods Process Evaluation Study

Background: An estimated 150 million people have mental health care needs in India, but only 15% are able to access care. Depression and anxiety contribute to a large proportion of mental morbidity. The Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health trial used a mobile-based clinical decision support system for primary care doctors and community health workers (CHWs) to identify and treat people at risk of depression, anxiety disorders, and self-harm. A community-based antistigma campaign was also delivered. The intervention led to improved remission rates for depression and anxiety and lower stigma scores. Objective: A process evaluation assessed (1) implementation fidelity, barriers, and facilitators; (2) perceptions of doctors and CHWs on the use of SMART Mental Health; and (3) the causal pathways that led to trial outcomes. Methods: A mixed methods evaluation combining backend program data and qualitative data was conducted. A total of 38 focus group discussions and 37 key informant interviews were conducted with primary doctors, CHWs, government officials, local community leaders, and research project staff. The data were coded and analyzed using a framework analysis approach based on the UK Medical Research Council guidance on process evaluations and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. Results: The intervention had high implementation fidelity. Across clusters, the median proportion of participants with at least 1 CHW follow-up was 98% (IQR 96.6%-100%). The referral rate for a psychiatrist was low (224/1697, 13.2%), and only 23.6% (53/224) of those referred visited the psychiatrist. The median exposure to antistigma audiovisual content was 84% (IQR 65.7%-95.9%). At the community level, key implementation barriers included cultural inhibitions in seeking mental health care and the unavailability of patients due to competing demands. Proximity and tight social connections between CHWs and their communities were important facilitators in seeking medical help. Doctor and CHW training, mentoring, and feedback provided by program staff were important facilitators to support the use of the digital health components by the health workforce. Conclusions: A complex intervention that included both community-based antistigma and clinical digital health interventions achieved high implementation fidelity. Key areas to consider for maintenance of such interventions include (1) the need for sustained community-based strategies to address stigma and other cultural barriers; (2) health workforce strengthening policies, including supportive supervision for CHWs and doctors to increase capability in the use of mental health digital health tools; and (3) strategies to improve access to specialist care for those with more complex care needs. Trial Registration: Clinical Trial Registry India CTRI/2018/08/015355; https://tinyurl.com/5r63suxp

May 7, 2026

Digital Therapeutic Content for Substance Use Disorder Treatment: Development and Evaluation Study

Background: Substance use disorders (SUDs) are a major public health concern, contributing to significant individual and societal costs. Despite this, the uptake of evidence-based pharmacologic and behavioral interventions remains limited. The digital delivery of SUD treatment has emerged as a potentially scalable way to reduce access barriers and increase treatment use. Existing digital therapeutic interventions are often created without clinician involvement, evidence-based materials, interdisciplinary input, or content review. The implementation of a structured and methodologically rigorous development process is needed across digital health interventions to help ensure patient-facing materials are validated, understandable, and actionable for the end user. Objective: This early report seeks to describe and evaluate an iterative, interdisciplinary, platform-agnostic process for adapting and refining existing print materials for digital therapeutic modules in SUD treatment. The a priori goal was to evaluate if a structured, human-centered approach would generate digital modules that were rated as understandable and actionable based on a validated assessment for written materials. Methods: Fourteen therapeutic modules were adapted from existing Mayo Clinic–written, patient-facing education materials originally developed by a board-certified addiction psychiatrist and a doctoral-level education specialist for clinical use. A team of 4 purposively recruited licensed alcohol and drug counselors with lived experience with a SUD, all in recovery, and a doctoral-level therapeutic specialist met weekly for one hour over a 6-month period to iteratively adapt this existing content for smartphone delivery (2‐3 hours per module). The process flow included selecting source material, restructuring content for viewing on a phone screen, simplifying language, improving organization and flow to promote understanding, and including specific actions users could take based on the content. The counselors then independently evaluated the modules using the Patient Education Materials Assessment Tool for printable materials (PEMAT-P). PEMAT-P scores for understandability and actionability were calculated as percentages, and descriptive statistics were used to summarize scores in aggregate and across modules. A target of >70% was set for each PEMAT-P domain, consistent with accepted benchmarking standards. Results: Mean understandability and actionability for all modules were 87.2% (SD 4.8%; range 81.4%‐96.9%) and 75.1% (SD 12.3%; range 57.1%‐95.0%), respectively, exceeding the recommended threshold. While all modules were adequately understandable, 35.7% (5/14) scored below the actionability threshold. Conclusions: This early report highlights the value of a human-centered, iterative process for adapting therapeutic materials for digital delivery in SUD treatment. Although the modules performed well overall on PEMAT-P benchmarks, actionability was less consistent than understandability, and aggregate scores masked weaknesses in several individual modules. This indicates that a standardized process does not guarantee actionable material across all content types. Involving current patients in this process may improve the end product by incorporating a perspective that was previously missed.

May 7, 2026

Oral Small-Molecule GLP-1s Linked to Deep Brain Activity and Reduced Cravings in Mice

Interest in glucagon-like peptide 1 receptor agonists (GLP-1s) continues to surge due to their effectiveness in reducing body weight and improving metabolic outcomes. This includes interest in small molecule oral GLP-1s which are more bioavailable and more easily manufactured than their injectable counterparts.

Now data from a new study in mice performed by scientists at the University of Virginia shows that this emerging class of weight-loss drugs suppress hedonic eating by modulating a reward circuit deep in the brain that is separate from previously described mechanisms that broadly affect appetite. The scientists believe that this pathway could be an avenue by which GLP-1s treat other dysfunctions in reward processing such as substance use disorders.

Details of the National Institutes of Health-funded study were published this week in a Nature paper titled “A brain reward circuit inhibited by next-generation weight-loss drugs in mice.” In it, the team reported that they investigated the small-molecule GLP-1s including Eli Lilly’s recently approved drug orforglipron, also known by the brand name Foundayo, as well as danuglipron, an oral GLP-1 that was being developed by Pfizer until the company decided to discontinue its development in 2025.

Previous studies that explored the effects of larger peptide GLP-1s such as semaglutide in the brain have found that they suppress hunger-driven eating by engaging networks in the hypothalamus and hindbrain. What has been less clear is the mechanism by which small-molecule GLP-1s work. “As the accessibility of these medications continues to rise and patient uptake increases, it’s crucial that we understand the neural mechanisms underlying the effects we’re seeing,” said Lorenzo Leggio, MD, PhD, clinical director of NIH’s National Institute on Drug Abuse.

The current study gets scientists one step closer to that goal. According to the paper, the scientists first used gene editing to modify the GLP-1 receptors of mice to make them more humanlike. They then administered orforglipron or danuglipron to the mice, and identified brain regions where the drugs induced activity. The results showed that in addition to inducing activity in familiar pathways, the drugs also triggered the central amygdala, a region associated with desire that is deeper in the brain than scientists previously thought GLP-1s could directly reach. Further testing showed that once activated, the central amygdala reduced the release of dopamine into key hubs of the brain’s reward circuitry during hedonic feeding.

“We’ve known that GLP-1 drugs suppress feeding behavior driven by energy demand,” said co-corresponding author Ali Guler, PhD, a professor of biology at the University of Virginia. “Now it seems oral small-molecule GLP-1s also dial back eating for pleasure by engaging a brain reward circuit.”

Given the effect of these drugs on eating for pleasure, future studies could explore whether small-molecule GLP-1s can also suppress cravings for other addictive substances. It is a question that the team hopes to explore in follow up studies focused specifically on substance use disorder.

The post Oral Small-Molecule GLP-1s Linked to Deep Brain Activity and Reduced Cravings in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.

May 7, 2026

Autism Screening Proposed for Children with Epilepsy

Children with epilepsy are up to 10 times more likely than others to also have autism, according to research that exposes the scale of the association between the two conditions.

The findings, in more than 30,000 children, stress the importance of screening for developmental concerns among those with epilepsy, so support can be delivered as early as possible.

The study, Developmental Medicine & Child Neurology, revealed that girls with autism spectrum disorder (ASD) were more likely than boys to also have epilepsy.

Higher rates of intellectual disability were also seen in children with autism who additionally had epilepsy, and they were also diagnosed with the neurodiversity at an earlier age.

“Our findings emphasize the importance of screening for autism in this population to support earlier diagnosis and timely intervention, both of which are key to improving long-term outcomes,” said senior investigator Elaine Wirrell, MD, from the Mayo Clinic.

ASD and epilepsy are complex disorders of neuronal connectivity that frequently co-occur because of shared molecular and biological mechanisms.

While the increased risk of ASD in children with epilepsy is well documented, there are gaps in knowledge around its incidence and prevalence, and risk factors for their co-occurrence.

To investigate further, Wirrell and team studied the medical records of 30,490 children in Olmsted County, Minnesota, of whom 257 (0.84%) were diagnosed with epilepsy before the age of 19 years.

They found that children with epilepsy were more likely have ASD across all three research and clinical definitions compared with other children, with this likelihood increased between six and 10-fold.

The prevalence was a corresponding 21.4% versus 3.2% using broad research criteria, 14.0% versus 1.6% across stricter research criteria, and 7.9% versus 0.7% for a clinical diagnosis.

Among children with autism, those also with epilepsy were more likely to have a lower IQ on standardized testing than those in whom epilepsy was absent (56.5% versus 15.4%). Specifically, an IQ of less than 70 was observed in 57.4% of children with co-occurring epilepsy and autism compared with only 15.4% autism alone.

Those with autism and epilepsy were also more often female than those with autism alone (38.2% versus 25.8%), and were identified with autism at a younger age, at a mean of seven years and five months versus eight years and eight months).

“These insights underscore the critical need for comprehensive and early screening protocols to better address and manage the intersection of autism and epilepsy, ensuring timely interventions and tailored support for affected individuals,” the researchers concluded.

The post Autism Screening Proposed for Children with Epilepsy appeared first on Inside Precision Medicine.

May 7, 2026

PMAT enhances sexual dimorphism of fear behaviors and facilitates female mice’s generalized contextual fear extinction

Enhanced signaling of dopamine and/or serotonin during highly arousing situations can be reduced in part by monoamine transporters, such as plasma membrane monoamine transporter (PMAT, Slc29a4). An absence of selective pharmacological inhibitors means genetically modified mice constitutively deficient in PMAT remain the best tool for studying PMAT’s organism-level functional effects. Fear conditioning is a high arousal process. Generalization of fear is evolutionarily advantageous, whereby information learned from one experience is applied to other new but similar encounters. Pathological fear generalization, in contrast, is a core feature of most anxiety disorders. Given our previous findings indicating PMAT function reduces male mice’s context fear and enhances extinction of female mice’s cued fear, we hypothesized PMAT would similarly reduce generalization (i.e., enhance discrimination) of context and cued fear in male and female mice, respectively. Our context and cued fear conditioning experiments in adult PMAT wildtype (+/+) and heterozygous (+/−) male and female mice partially supported our hypotheses. We discovered PMAT facilitates extinction of contextually generalized fear, plus subsequent extinction of context-specific fear, selectively in females. Moreover, when specific fear cues or contexts were temporally presented before cues or contexts that were similar enough to make generalization possible, PMAT enhanced biological sex differences. Growing evidence reports common PMAT polymorphisms elicit measurable effects when PMAT function is reduced. Thus, we suspect future experiments may reveal positive associations between PMAT polymorphisms and risk for anxiety disorder symptoms, particularly in people assigned female at birth. Inclusion of these genetic variations in pharmacogenomic analyses may prove therapeutically beneficial.

May 7, 2026

Identifying clinical features associated with electroconvulsive therapy response in adolescents with major depressive disorder using machine learning

BackgroundElectroconvulsive therapy (ECT) is an effective treatment for adolescent major depressive disorder (MDD), but its efficacy varies. This study utilized machine learning (ML) to identify baseline clinical factors associated with poor ECT response.MethodsWe retrospectively enrolled 503 adolescent MDD patients. A poor response was defined as a <50% reduction on the Hamilton Depression Scale (HAMD-24). The optimal ML algorithm (Random Forest, RF) was selected from nine candidates and then simplified using recursive feature elimination (RFE) and interpreted via Shapley Additive Explanations (SHAP).ResultsA simplified model using two baseline features—the neutrophil-to-platelet ratio (NPR) and pre-treatment HAMD score—achieved an AUC of 0.731 on the testing set, comparable to the full-feature model (AUC: 0.751). SHAP analysis revealed that a lower baseline NPR and a lower pre-treatment HAMD score were associated with a poor response. Furthermore, retrospective statistical comparisons revealed that patients in the poor response group completed significantly fewer ECT sessions than those in the good response group.ConclusionsWe developed a concise explanatory model demonstrating that routine clinical data available at admission (blood NPR and HAMD score) can effectively stratify the risk of poor ECT efficacy. Crucially, identifying these high-risk patients early empowers clinicians to implement targeted management, ensuring they complete a full and adequate course of ECT to maximize therapeutic benefits and prevent premature termination.

May 7, 2026

A two-decade bibliometric analysis (2004–2024) of parental factors in the context of internet gaming disorder research

ObjectiveThis is the first targeted bibliometric analysis which explores the development of scientific production on the relationship between parenting and Internet Gaming Disorder (IGD) over twenty years, emphasizing the central role of the family context in the etiology and maintenance of IGD.MethodsPapers indexed in Scopus and Web of Science databases from 2004 to December 31, 2024, were analyzed using the PRISMA guidelines, the R package Bibliometrix, and VOSviewer. A comprehensive search strategy was developed using Boolean operators to capture variations of parental and gaming-related terminology. Records were exported in BibTeX format and were merged and cleaned to remove duplicates before the analysis. A descriptive bibliometric analysis, bibliometric mapping, and content analysis were conducted to identify trends and thematic clusters. The analysis included 389 publications.ResultsThe most cited papers confirm the association of low parental warmth, family dysfunction, and comorbid psychiatric symptoms with a higher risk of IGD. Thematic mapping reveals six dominant clusters covering the conceptualization and diagnosis of IGD, parental mediation and virtual environment, psychological vulnerability and mental health, parenting and attachment, parenting styles and self-control, and problematic screen-related behaviors, and a strong concentration of publications in China, Germany, and the USA. The analysis also revealed an increase in publication output after 2013, with a notable acceleration following the inclusion of gaming disorder in the International Classification of Diseases 11th Revision (ICD-11).ConclusionThe bibliometric analysis reveals the rapid growth of research on parenting and IGD, highlighting the multifactorial nature of the disorder where dysfunctional family relationships increase risk, while supportive ones reduce it. Despite progress, longitudinal studies are needed for better understanding of causality and interventions.

May 7, 2026

[Articles] Who receives psychiatry-focused pharmacogenomic testing, and is it associated with prescribing patterns and acute care utilisation in depression? Real-world evidence from a large health system

In routine clinical practice, PGx testing is preferentially used in youth and adults with clinically complex histories and is associated with shifts in antidepressant prescribing patterns. Exploratory findings suggest hypothesis-generating signals of reduced psychiatric ED utilisation among patients with higher psychiatric complexity, which requires further confirmation. Observed racial disparities highlight the need for earlier and more equitable implementation. Prospective studies incorporating symptom-level and safety outcomes are needed to determine whether PGx-guided prescribing translates into meaningful clinical benefit.

May 7, 2026

Noise, air pollution exposure and attention-deficit/hyperactivity disorder: a meta-analysis

ObjectiveThis meta-analysis evaluated the associations between noise exposure, air pollutants, and attention-deficit/hyperactivity disorder (ADHD) in children, aiming to inform future prevention strategies.MethodsStudies were systematically retrieved from CNKI, Wanfang, PubMed, Web of Science, Embase, and the Cochrane Library, covering publications from inception to November 2025. Heterogeneity was assessed using Cochran’s Q test and the I² statistic. Subgroup analyses, meta-regression, and sensitivity analyses were performed to evaluate the robustness of the findings.ResultsNoise exposure was associated with a small increase in ADHD risk (odds ratio [OR] = 1.03, 95% confidence interval [CI]: 1.01–1.05), with stronger associations for childhood exposure, whereas prenatal exposure showed no significant effect. Given the modest effect size, this finding should be interpreted cautiously. Particulate matter (PM2.5 and PM10) was significantly associated with ADHD in continuous-exposure models—PM2.5 (OR = 1.32, 95% CI: 1.16–1.50) and PM10 (OR = 1.47, 95% CI: 1.15–1.87). In dichotomous models, PM2.5 was not significant, while PM10 remained positively associated (OR = 1.58, 95% CI: 1.11–2.26). Elevated nitrogen dioxide (NO2) exposure was also associated with a modest increase in ADHD risk (OR = 1.11, 95% CI: 1.02–1.20), whereas nitrogen oxides (NOx), ozone (O3), and sulfur dioxide (SO2) did not show significant associations.ConclusionsNoise and several air pollutants (PM2.5, PM10, and NO2) were significantly associated with increased ADHD risk, particularly during childhood exposure. Other pollutants, including O3 and SO2, did not demonstrate significant effects. These findings suggest that environmental noise and several air pollutants may be associated with ADHD; however, some observed associations, particularly for noise and NO2, were modest in magnitude and should be interpreted cautiously. These results reflect observational associations rather than evidence of a strong or causal effect, while the evidence for some pollutants remains limited or inconclusive. Further research is needed to clarify pollutant-specific associations and the role of exposure timing.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42024593274, identifier CRD42024593274; https://www.crd.york.ac.uk/PROSPERO/view/CRD42025632899, identifier CRD42025632899.

May 6, 2026

At-Home Blood Test Screens for Early Dementia

A simple finger-prick blood test at home combined with online cognitive tests can reveal signs of Alzheimer’s disease, providing a convenient way to screen for early dementia.

The postal blood test, outlined in Nature Communications, is used to measure levels of two blood biomarkers linked with cognitive function: phosphorylated tau at amino acid 217 (p-tau217) and Glial Fibrillary Acidic Protein (GFAP).

It could provide a way to screen for dementia at home and act as a triage resource to identify those at risk earlier and tailor treatments more effectively, particularly in remote or unsupervised settings.

“This work raises the potential for screening people for their risk without the need for clinic visits or complex clinical assessments,” said lead researcher Anne Corbett, PhD, from the University of Exeter.

“It would ensure the people at highest risk could be prioritized for monitoring and diagnosis, unlocking the best support and treatment for those that need it most.”

While blood biomarkers are increasingly being used to diagnose Alzheimer’s disease, scalable tools are needed to reach the 99% of individuals with early cognitive impairment who are not seen in specialist healthcare services.

In an attempt to develop these further, Corbett and team conducted a study involving 174 people, of whom 146 had normal cognition and 28 had dementia.

All were participants in the PROTECT study, a larger investigation of more than 30,000 adults that aims to understand how healthy brains age and why people develop dementia.

Blood samples were collected at home using self-administered capillary blood tests, which were sent for p-tau 217 and GFAP lab testing. Venous blood samples were also available for 40 patients.

p-tau217 has previously been highly accurate at detecting Alzheimer’s disease pathology and is approved by U.S. regulators for symptomatic patients undergoing investigation for cognitive complaints.

GFAP is associated with broader cognitive decline and has been shown to be associated with Aβ deposition and progression of mild cognitive impairment to Alzheimer’s disease.

Brain performance tests were found to correlate with levels of both proteins, with p-tau217 showing the strongest association.

Capillary p-tau217 was significantly higher in people with dementia compared to those without and was significantly associated with cognitive performance and function.

A combination of an 85% specificity threshold for capillary p-tau217 85% and episodic memory performance one standard deviation (SD) below benchmarked norms identified 9% of participants who were at potentially high risk, and who also showed significantly higher impairment in cognition and function.

Importantly, this threshold for impairment of episodic memory indicated a much milder level of impairment than the 1.5 SD change required to identify people with mild cognitive impairment, revealing its potential ability to spot signs at a preclinical stage.

Unexpectedly, even though ptau217 and GFAP both identified individuals with cognitive impairment, there was only a modest overlap in individuals who were positive for both GFAP and p-tau217, with GFAP identifying a different group of at-risk individuals. GFAP biomarker appeared to be associated with vascular risk, unlike p-tau217.

Researcher Clive Ballard, MD, PhD, also at Exeter, said: “Our approach of combining our robust cognitive testing with measuring proteins via a postal blood test could provide a straightforward, efficient and cost-effective method to reach large numbers of people in the community who would not otherwise be prioritized for the next steps of diagnosis or support and to optimize the clinical pathway to enable early detection of those at highest risk.”

The post At-Home Blood Test Screens for Early Dementia appeared first on Inside Precision Medicine.