Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.

We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).

Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.

Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

Bathing intensive care unit (ICU) patients with chlorhexidine gluconate (CHG) decreases healthcare-associated infections (HAIs). The optimal method of CHG bathing remains undefined.

Prospective crossover study comparing CHG daily bathing with 2% CHG-impregnated cloths versus 4% CHG solution. In phase 1, from January 2020 through March 2020, 1 ICU utilized 2% cloths, while the other ICU utilized 4% solution. After an interruption caused by the coronavirus disease 2019 pandemic, in phase 2, from July 2020 through September 2020, the unit CHG bathing assignments were reversed. Swabs were performed 3 times weekly from patients’ arms and legs to measure skin microbial colonization and CHG concentration. Other outcomes included HAIs, adverse reactions, and skin tolerability.

411 assessments occurred after baths with 2% cloth, and 425 assessments occurred after baths with 4% solution. Average microbial colonization was 691 (interquartile range 0, 30) colony-forming units per square centimeter (CFU/cm2) for patients bathed with 2% cloths, 1,627 (0, 265) CFUs/cm2 for 4% solution, and 8,519 (10, 1130) CFUs/cm2 for patients who did not have a CHG bath (P < .001). Average CHG skin concentration (parts per million) was 1300.4 (100, 2000) for 2% cloths, 307.2 (30, 200) for 4% solution, and 32.8 (0, 20) for patients without a recorded CHG bath. Both CHG bathing methods were well tolerated. Although underpowered, no difference in HAI was noted between groups.

Either CHG bathing method resulted in a significant decrease in microbial skin colonization with a greater CHG concentration and fewer organisms associated with 2% CHG cloths.

The majority of studies of mental health interventions for young adolescents have only evaluated short-term benefits. This study evaluated the longer-term effectiveness of a non-specialist delivered group-based intervention (Early Adolescent Skills for Emotions; EASE) to improve young adolescents’ mental health.

In this single-blind, parallel, controlled trial, Syrian refugees aged 10-14 years in Jordan who screened positive for psychological distress were randomised to receive either EASE or enhanced usual care (EUC). Primary outcomes were scores on the Paediatric Symptom Checklist (PSC) assessed at Week 0, 8-weeks, 3-months, and 12 months after treatment. Secondary outcomes were disability, posttraumatic stress, school belongingness, wellbeing, and caregivers’ reports of distress, parenting behaviour, and their perceived children’s mental health.

Between June, 2019 and January, 2020, 185 adolescents were assigned to EASE and 286 to EUC, and 149 (80.5%) and 225 (78.7%) were retained at 12 months, respectively. At 12 months there were no significant differences between treatment conditions, except that EASE was associated with less reduction in depression (estimated mean difference -1.6, 95% CI –3.2 to -0.1; p=.03; effect size, -0.3), and a greater sense of school belonging (estimated mean difference -0.3, 95% CI –5.7 to -0.2; p=.03; effect size, 5.0).

Although EASE led to significant reductions in internalising problems, caregiver distress, and harsh disciplinary parenting at 3-months, these improvements were not maintained at 12 months relative to EUC. Scalable psychological interventions for young adolescents need to consider their ongoing mental health needs. Prospectively registered: ACTRN12619000341123.

Depression and anxiety are the leading contributors to the global burden of disease among young people, accounting for over a third (34.8%) of years lived with disability. Yet there is limited evidence for interventions that prevent adolescent depression and anxiety in low- and middle-income countries (LMICs), where 90% of adolescents live. This article introduces the ‘Improving Adolescent mentaL health by reducing the Impact of poVErty (ALIVE)’ study, its conceptual framework, objectives, methods and expected outcomes. The aim of the ALIVE study is to develop and pilot-test an intervention that combines poverty reduction with strengthening self-regulation to prevent depression and anxiety among adolescents living in urban poverty in Colombia, Nepal and South Africa.

This aim will be achieved by addressing four objectives: (1) develop a conceptual framework that identifies the causal mechanisms linking poverty, self-regulation and depression and anxiety; (2) develop a multi-component selective prevention intervention targeting self-regulation and poverty among adolescents at high risk of developing depression or anxiety; (3) adapt and validate instruments to measure incidence of depression and anxiety, mediators and implementation parameters of the prevention intervention; and (4) undertake a four-arm pilot cluster randomised controlled trial to assess the feasibility, acceptability and cost of the selective prevention intervention in the three study sites.

The contributions of this study include the active engagement and participation of adolescents in the research process; a focus on the causal mechanisms of the intervention; building an evidence base for prevention interventions in LMICs; and the use of an interdisciplinary approach.

By developing and evaluating an intervention that addresses multidimensional poverty and self-regulation, ALIVE can make contributions to evidence on the integration of mental health into broader development policy and practice.

Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.

Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.

In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.

This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.

There is increasing evidence that brief psychological interventions delivered by lay providers can reduce common mental disorders in the short-term. This study evaluates the longer-term impact of a brief, lay provider delivered group psychological intervention (Group Problem Management Plus; gPM+) on the mental health of refugees and their children's mental health.

This single-blind, parallel, controlled trial randomised 410 adult Syrians in Azraq Refugee Camp in Jordan who screened positive for distress and impaired functioning to either five sessions of gPM+ or enhanced usual care (EUC). Primary outcomes were scores on the Hopkins Symptom Checklist-25 (HSCL-25; depression and anxiety scales) assessed at baseline, 6 weeks, 3 months and 12 months Secondary outcomes included disability, posttraumatic stress, personally identified problems, prolonged grief, prodromal psychotic symptoms, parenting behaviour and children's mental health.

Between 15 October 2019 and 2 March 2020, 204 participants were assigned to gPM + and 206 to EUC, and 307 (74.9%) were retained at 12 months. Intent-to-treat analyses indicated that although participants in gPM + had greater reductions in depression at 3 months, at 12 months there were no significant differences between treatment arms on depression (mean difference −0.9, 95% CI −3.2 to 1.3; p = 0.39) or anxiety (mean difference −1.7, 95% CI −4.8 to −1.3; p = 0.06). There were no significant differences between conditions for secondary outcomes except that participants in gPM + had greater increases in positive parenting.

The short-term benefits of a brief, psychological programme delivered by lay providers may not be sustained over longer time periods, and there is a need for sustainable programmes that can prolong benefits gained through gPM + .

Because of the high burden of untreated mental illness in humanitarian settings and low- and middle-income countries, scaling-up effective psychological interventions require a cultural adaptation process that is feasible and acceptable. Our adaptation process incorporates changes into both content and implementation strategies, with a focus on local understandings of distress and treatment mechanisms of action.

Building upon the ecological validity model, we developed a 10-step process, the mental health Cultural Adaptation and Contextualization for Implementation (mhCACI) procedure, and piloted this approach in Nepal for Group Problem Management Plus (PM+), a task-sharing intervention, proven effective for adults with psychological distress in low-resource settings. Detailed documentation tools were used to ensure rigor and transparency during the adaptation process.

The mhCACI is a 10-step process: (1) identify mechanisms of action, (2) conduct a literature desk review for the culture and context, (3) conduct a training-of-trainers, (4) translate intervention materials, (5) conduct an expert read-through of the materials, (6) qualitative assessment of intervention population and site, (7) conduct practice rounds, (8) conduct an adaptation workshop with experts and implementers, (9) pilot test the training, supervision, and implementation, and (10) review through process evaluation. For Group PM+, key adaptations were harmonizing the mechanisms of action with cultural models of ‘tension’; modification of recruitment procedures to assure fit; and development of a skills checklist.

A 10-step mhCACI process could feasibly be implemented in a humanitarian setting to rapidly prepare a psychological intervention for widespread implementation.

Despite recent global attention to mental health and psychosocial support services and a growing body of evidence-support interventions, few mental health services have been established at a regional or national scale in low- and middle-income countries (LMIC). There are myriad challenges and barriers ranging from testing interventions that do not target priority needs of populations or policymakers to interventions that cannot achieve adequate coverage to decrease the treatment gap in LMIC.

We propose a ‘roadmap to impact’ process that guides planning for interventions to move from the research space to the implementation space.

We establish four criteria and nine associated indicators that can be evaluated in low-resource settings to foster the greatest likelihood of successfully scaling mental health and psychosocial interventions. The criteria are relevance (indicators: population need, cultural and contextual fit), effectiveness (change in mental health outcome, change in hypothesised mechanism of action), quality (adherence, competence, attendance) and feasibility (coverage, cost). In the research space, relevance and effectiveness need to be established before moving into the implementation space. In the implementation space, ongoing monitoring of quality and feasibility is required to achieve and maintain a positive public health impact. Ultimately, a database or repository needs to be developed with these criteria and indicators to help researchers establish and monitor minimum benchmarks for the indicators, and for policymakers and practitioners to be able to select what interventions will be most likely to succeed in their settings.

A practicable roadmap with a sequence of measurable indicators is an important step to delivering interventions at scale and reducing the mental health treatment gap around the world.

The PRogramme for Improving Mental Health carE (PRIME) evaluated the process and outcomes of the implementation of a mental healthcare plan (MHCP) in Chitwan, Nepal.

To describe the process of implementation, the barriers and facilitating factors, and to evaluate the process indicators of the MHCP.

A case study design that combined qualitative and quantitative methods based on a programme theory of change (ToC) was used and included: (a) district-, community- and health-facility profiles; (b) monthly implementation logs; (c) pre- and post-training evaluation; (d) out-patient clinical data and (e) qualitative interviews with patients and caregivers.

The MHCP was able to achieve most of the indicators outlined by the ToC. Of the total 32 indicators, 21 (66%) were fully achieved, 10 (31%) partially achieved and 1 (3%) were not achieved at all. The proportion of primary care patients that received mental health services increased by 1200% over the 3-year implementation period. Major barriers included frequent transfer of trained health workers, lack of confidential space for consultation, no mental health supervision in the existing system, and stigma. Involvement of Ministry of Health, procurement of new psychotropic medicines through PRIME, motivation of health workers and the development of a new supervision system were key facilitating factors.

Effective implementation of mental health services in primary care settings require interventions to increase demand for services and to ensure there is clinical supervision for health workers, private rooms for consultations, a separate cadre of psychosocial workers and a regular supply of psychotropic medicines.

Current coverage of mental healthcare in low- and middle-income countries is very limited, not only in terms of access to services but also in terms of financial protection of individuals in need of care and treatment.

To identify the challenges, opportunities and strategies for more equitable and sustainable mental health financing in six sub-Saharan African and South Asian countries, namely Ethiopia, India, Nepal, Nigeria, South Africa and Uganda.

In the context of a mental health systems research project (Emerald), a multi-methods approach was implemented consisting of three steps: a quantitative and narrative assessment of each country's disease burden profile, health system and macro-fiscal situation; in-depth interviews with expert stakeholders; and a policy analysis of sustainable financing options.

Key challenges identified for sustainable mental health financing include the low level of funding accorded to mental health services, widespread inequalities in access and poverty, although opportunities exist in the form of new political interest in mental health and ongoing reforms to national insurance schemes. Inclusion of mental health within planned or nascent national health insurance schemes was identified as a key strategy for moving towards more equitable and sustainable mental health financing in all six countries.

Including mental health in ongoing national health insurance reforms represent the most important strategic opportunity in the six participating countries to secure enhanced service provision and financial protection for individuals and households affected by mental disorders and psychosocial disabilities.

D.C. is a staff member of the World Health Organization.

Little is known about the household economic costs associated with mental, neurological and substance use (MNS) disorders in low- and middle-income countries.

To assess the association between MNS disorders and household education, consumption, production, assets and financial coping strategies in Ethiopia, India, Nepal, Nigeria, South Africa and Uganda.

We conducted an exploratory cross-sectional household survey in one district in each country, comparing the economic circumstances of households with an MNS disorder (alcohol-use disorder, depression, epilepsy or psychosis) (n = 2339) and control households (n = 1982).

Despite some heterogeneity between MNS disorder groups and countries, households with a member with an MNS disorder had generally lower levels of adult education; lower housing standards, total household income, effective income and non-health consumption; less asset-based wealth; higher healthcare expenditure; and greater use of deleterious financial coping strategies.

Households living with a member who has an MNS disorder constitute an economically vulnerable group who are susceptible to chronic poverty and intergenerational poverty transmission.

D.C. is a staff member of the World Health Organization. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policy or views of the World Health Organization.

Evidence shows benefits of psychological treatments in low-resource countries, yet few government health systems include psychological services.

Evaluating the clinical value of adding psychological treatments, delivered by community-based counsellors, to primary care-based mental health services for depression and alcohol use disorder (AUD), as recommended by the Mental Health Gap Action Programme (mhGAP).

Two randomised controlled trials, separately for depression and AUD, were carried out. Participants were randomly allocated (1:1) to mental healthcare delivered by mhGAP-trained primary care workers (psychoeducation and psychotropic medicines when indicated), or the same services plus individual psychological treatments (Healthy Activity Program for depression and Counselling for Alcohol Problems). Primary outcomes were symptom severity, measured using the Patient Health Questionnaire – 9 item (PHQ-9) for depression and the Alcohol Use Disorder Identification Test for AUD, and functional impairment, measured using the World Health Organization Disability Assessment Schedule (WHODAS), at 12 months post-enrolment.

Participants with depression in the intervention arm (n = 60) had greater reduction in PHQ-9 and WHODAS scores compared with participants in the control (n = 60) (PHQ-9: M = −5.90, 95% CI −7.55 to −4.25, β = −3.68, 95% CI −5.68 to −1.67, P < 0.001, Cohen's d = 0.66; WHODAS: M = −12.21, 95% CI −19.58 to −4.84, β = −10.74, 95% CI −19.96 to −1.53, P= 0.022, Cohen's d = 0.42). For the AUD trial, no significant effect was found when comparing control (n = 80) and intervention participants (n = 82).

Adding a psychological treatment delivered by community-based counsellors increases treatment effects for depression compared with only mhGAP-based services by primary health workers 12 months post-treatment.

None.