Active Ingredients in Digital Cognitive Interventions: Integrating Dismantling Designs With Mechanistic Neuroscience

Digital cognitive interventions (DCIs) have emerged as scalable approaches for treating cognitive dysfunction across psychiatric, neurological, and aging populations. Despite growing evidence of efficacy, little is known about which intervention components drive therapeutic effects or through which neurocognitive mechanisms they operate. As a result, null findings are often difficult to interpret, making it unclear whether interventions failed to engage their intended targets, or whether the targets themselves are not causally related to meaningful outcomes. This limits intervention refinement, comparative evaluation, and precision personalization. Here, we argue that DCI research should shift from broad efficacy testing toward mechanistic trials designed to identify active ingredients—the intervention components responsible for engaging prespecified neurocognitive targets and producing clinically meaningful benefits. We propose adapting dismantling design methodology from psychotherapy research in order to integrate Research Domain Criteria constructs, mechanistic neuroscience, and high-resolution digital behavioral data to identify factors driving cognitive and functional outcomes. This approach aligns with the National Institute of Mental Health experimental therapeutics framework by explicitly linking target specification and target engagement with downstream clinical and functional outcomes. Mechanistic dismantling trials can determine whether specific DCI features, including adaptive difficulty, reward schedules, feedback contingencies, task variability, cognitive targets, and human support, are necessary, sufficient, or synergistic for engaging neural circuitry and producing durable and clinically meaningful transfer. Beyond optimizing intervention design, such studies may transform null or negative trials into mechanistically interpretable findings, while clarifying disease mechanisms and supporting the development of personalized, optimized, and usable DCIs.
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A hybrid implementation-effectiveness study of a school-based intervention for promoting health and well-being in low-resource settings: the ISOBAR study protocol

IntroductionSchool-based interventions can improve adolescent health outcomes and tackle the growing burden of non-communicable diseases (NCDs) in low-and-middle-income countries (LMICs). Results to date are variable, partly due to lack of cultural adaptation of Westernised models and limited focus on implementation processes. The aim of the ISOBAR project is to develop, implement, and test a school-based intervention to address the emergence of mental and physical (i.e., nutritional, physical inactivity) health problems in LMICs. The three-stage intervention comprises (1) assessment for mental and physical health problems, (2) universal health literacy, and (3) indicated counselling.Methods and analysisThe ISOBAR multi-site project comprises three phases: (1) pre-intervention (co-development and cultural adaptation of the intervention); (2) implementation of the intervention; and (3) post-intervention evaluation. The intervention will be delivered using a staggered roll-out design to introduce the intervention sequentially to three schools per site (nine in total) in Chennai, Gujarat (India), and Ibadan (Nigeria). Each school will receive the intervention by the end of the study period. Local teams will recruit 200 adolescents per school (Total n=1, 800). All adolescents (in intervention and control conditions) will be assessed for mental health/behavioural problems and nutritional/weight problems at baseline. Adolescents in the intervention school will receive the universal health literacy intervention (main cohort), and those adolescents reaching pre-determined thresholds on mental health and/or nutritional indices (sub-cohort) will be referred to school-based counselling support. A suite of assessments will be conducted throughout the study period including: (1) intervention effectiveness (e.g., impact on help-seeking, weight, and mental health and behavioural outcomes); (2) implementation processes (e.g., facilitators and barriers) and outcomes (e.g., acceptability, appropriateness, sustainability); and (3) cost-effectiveness.Ethics and disseminationThe study was approved by the University of Warwick’s Biomedical and Scientific Research Ethics Committee (BSREC 36/23-24) and the institutional ethics committees of all participating sites. Research findings will be disseminated through peer reviewed scientific publications, public announcements in local communities, policy briefings, print and online media, and institutional and professional social media accounts and websites.

Coping styles and mental health outcomes in partners who have experienced a perinatal loss: a longitudinal study

Perinatal loss is common, but little is known about its impact on partners during the grieving process. This study examined psychological outcomes and coping strategies among recently bereaved partners (≤6 months post-loss; N = 73) at baseline (T1) and six-month follow-up (T2) via online survey. Participants were predominantly male (78%) and typically aged 25–44 (90%), and had experienced a range of perinatal losses (<20 weeks’ gestation to 28 days of life). Grief and depression symptoms were assessed using the Perinatal Grief Scale (PGS) and PHQ-9 respectively, and multivariate regression analyses examined the role of coping styles, demographic characteristics, and loss-related factors. Participants reported varying levels of grief and depression symptoms, with 38% displaying moderate-to-severe depression symptoms at follow-up. Across the cohort, participants reported using a range of coping strategies; however, avoidant coping was uniquely associated with higher grief and depression scores at baseline (PHQ-9: β = .30, p = .007; PGS: β = .49, p <.001). Avoidant coping also predicted poorer grief and depression outcomes at follow-up, although these relationships were no longer significant after controlling for baseline symptoms. Additionally, stillbirth, female gender, and younger age were associated with greater psychological distress at baseline across outcomes (β = .21–.32, p ≤.05). Associations between gender, stillbirth, and psychological outcomes remained at follow-up, although these did not reach conventional levels of statistical significance (β = .24–.40, p ≤.073). These findings highlight the psychological impact of perinatal loss on partners and underscore the importance of improving access to support for this group. Avoidant coping may represent a key target for intervention. Future research should further investigate factors influencing grief trajectories and identify effective forms of support for bereaved partners.

Occupational burnout and risk of suicidality in healthcare professionals: a PRISMA-guided systematic review

BackgroundBurnout, an occupational phenomenon resulting from chronic workplace stress that has not been successfully managed, is increasingly recognized as a critical threat to the mental health of healthcare professionals. Prolonged exposure to work-related stressors may increase the risk of suicidality, including suicidal ideation, suicide attempts, and suicide deaths. This systematic review aimed to synthesize existing evidence on the association between burnout and suicidality in healthcare professionals and to identify vulnerable subgroups and intervention priorities.MethodsWe conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (PROSPERO registration: CRD420251037488). PubMed, Scopus, Web of Science, and PsycINFO were searched for studies published between January 2005 and December 2024. Eligible studies included healthcare professionals and, where methodologically relevant, closely related high-stress occupational populations used as comparator cohorts assessed with validated burnout instruments and reporting suicidality or closely related suicide-proximal psychological outcomes. Data were extracted independently by two reviewers, and risk of bias was evaluated using the Newcastle–Ottawa Scale. Where appropriate, findings were synthesized narratively and through meta-analysis.ResultsA total of 29 studies met the inclusion criteria and 10 studies were included in the meta-analysis. Strong associations were consistently observed between burnout and suicidality, with emotional exhaustion and depersonalization emerging as the most robust predictors. Reduced personal accomplishment demonstrated weaker or inverse associations. Nurses and physicians were identified as particularly vulnerable, with pandemic-era studies reporting higher effect sizes compared to pre-pandemic research. Overall methodological quality was moderate to high, and heterogeneity was partly explained by profession, region, and burnout instrument used.ConclusionsBurnout, particularly emotional exhaustion and depersonalization, is consistently associated with increased suicidality among healthcare professionals, with supporting evidence from related high-stress occupational populations. Vulnerable groups include women clinicians, younger professionals, and those engaged in rotating or night-shift work. These findings highlight the need for systematic burnout surveillance, confidential access to mental health support, and organizational reforms such as safe staffing ratios and workload regulation. Integrating suicide-prevention strategies into occupational health frameworks is urgently required to protect clinician wellbeing and sustain healthcare system resilience.

A Web-Based Self-Management Intervention for Return-to-Work Among Persons With Common Mental Disorders on Sick Leave: Case Study of mWorks

Background: mWorks is a co-designed, web-based self-management intervention developed to empower persons with common mental disorders who are on sick leave during the return-to-work process. However, limited knowledge of how mWorks is delivered and engaged with in real-world settings constrains further development and implementation. In line with the Medical Research Council framework for complex intervention evaluation, such an approach is required to examine (1) contextual factors influencing implementation, (2) fidelity and variation in delivery, and (3) how service users and professionals experience and respond to the intervention. Objective: This study aimed to evaluate the process of implementing mWorks, specifically focusing on assessing the intervention’s delivery in relation to the context, implementation process, and mechanisms of impact. Methods: This single-case study was bounded by the delivery period of 10 weeks in a primary and specialist mental health service context. During this period, return-to-work professionals (n=2) and service users (n=6) collaborated to initiate mWorks usage. Both qualitative and quantitative methods were used to triangulate multiple data sources. Results: The pandemic and mental health problems posed contextual barriers, particularly during recruitment. However, perceptions of mWorks as a credible and relevant intervention facilitated its implementation. The delivery was performed according to plan, with minimal adaptations. All users adhered to the intervention, and dialogue meetings were highly valued. mWorks was used flexibly according to users’ needs, both during sick leave and at work. The potential impacts included a transformative process for users, fostering acceptance, self-esteem, self-compassion, and a sense of control. It also had the potential to prevent mental ill health, transform negatives into positives, facilitate disclosure of mental health, and support goal setting. The use of quantitative measures for empowerment, engagement, self-efficacy, depression stigma, and quality of life proved feasible and supported the assumptions and direction of results. Conclusions: The recruitment stage of the implementation program encountered significant contextual barriers. However, once the delivery stage began, the implementation of mWorks proved to be feasible. Despite the limited scope of this study, with its small number of participants, the triangulation of data suggests that both users and professionals benefited from mWorks.
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