Optimising the potential of mindfulness programs in schools: Learning from implementation science

There is a growing need for the provision of mental health services for young people in schools. A number of evidence-based practices (EBPs) now exist for schools to choose from to address their pupils’ mental health needs. However, when such EBPs are introduced into schools, their effectiveness can be lacking and weakened. Implementation science suggests that without effective implementation strategies, the success of EBPs in schools may be limited. The transfer of knowledge into practice is a difficult and challenging process, often referred to as the ‘science to service gap’. To support the mental health of young people, there is a need not just for EBPs but also for evidence-based implementation. Mindfulness training (MT) is a promising intervention for young people that is currently being introduced to a number of schools across the UK, and internationally. The primary aim of this doctoral work was to understand and examine MT implementation experiences in order to identify the determinants of, and potential ways to promote, the early implementation stages of MT in schools. The first study in this doctoral work examined how far a knowledge broker, sharing implementation related knowledge, could impact the implementation decisions made by a steering group (SG) responsible for implementing a mindfulness program across schools in Cumbria, UK. SG meetings were attended for 14 months and meeting minutes, notes and audio recordings were recorded and analysed for “key moments” and “key outcomes”. A second related analysis of this SG activity explored, via interviews and thematic analysis, the perceived opportunities and barriers for the SG to act as an implementation team. Study 3 aimed to identify the determinants of MT early implementation success in five secondary schools by using the Consolidated Framework for Implementation Research (CFIR). Interviews were conducted with school staff responsible for implementing MT at two time points across 6 months. The schools’ implementation progress was recorded, and the CFIR was used to code the data for 38 implementation constructs. Usefulness of the CFIR was assessed. Finally, in Study 4 the findings of the previous studies were synthesised with the implementation science literature to inform the development of a preliminary implementation framework to promotes the successful implementation of MT in (secondary) schools in order to improve their usefulness in such complex settings. Findings from Study 1 and 2 suggested that SGs responsible for implementing school public health programs can learn about implementation and then apply this new knowledge to their program. Sharing knowledge with stakeholders responsible for implementing public health programs may be a viable and effective implementation promotion strategy. Having a strong engagement strategy and good relationships with schools can facilitate this process. SGs influence over general school capacity and external funding may be limited and hinder their ability to impact overall implementation. More work is needed to understand how SGs may be empowered to influence general capacity, funding, and have better linkages to other stakeholders involved in their program’s overall provision. Findings from Study 3 indicated that there are a number of implementation related constructs which seem to distinguish between schools which implement MT well and schools which do not. The CFIR was a useful tool for identifying the barriers and facilitator to EBPs in schools and which barriers and facilitators seem to distinguish implementation success between schools the most. School leadership plays a pivotal role in ensuring implementation success. Who should be solely responsible for the successful implementation of EBPs in schools is less clear but it may be that a concerted effort on the part of program designers, program funders and school leadership might be required to ensure programs are implemented well. Study 4 indicated that implementation frameworks designed specifically for school leaders are likely to be useful but what motivates school leaders to use them is less clear. Further research into ways of promoting the use of implementation guidance by school leaders is needed

HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner

Construct validity of the Brazilian version of the Externalizing Spectrum Inventory: evidence from a university student sample

BACKGROUND: Externalizing is a dimension of individual differences that undergirds and unites aggressive and impulsive personality traits to psychopathological disorders related to substance use and antisocial behavior. OBJECTIVES: The present study aims to establish parameters of construct validity for the Brazilian version of the Externalizing Spectrum Inventory. METHOD: This is a psychometrical correlacional study design. Two classical techniques of construct representation were implemented: unweighted least squares exploratory factor analysis and internal consistency analysis. The sample consisted of 258 participants of both sexes, from different undergraduate majors in two public universities in the state of Minas Gerais. RESULTS: As expected in theoretical grounds, common factor analysis revealed a one second-order factor (externalizing dimension) with three subfactor structure (substance, antisocial and impulsivity/alienation dimensions). The alfa coefficients were very high, with indexes greater than 0,9 for the three subfactor as well as for the general factor. DISCUSSION: Taken together, results bring evidences of validity and reliability of the Brazilian version of the Externalizing Spectrum Inventory in regard to it applicability in university students.CONTEXTO: Externalização é uma dimensão das diferenças individuais que dá substrato e unifica traços impulsivos e agressivos de personalidade a transtornos mentais relacionados ao uso de substância e à conduta antissocial. OBJETIVOS: O presente estudo objetivou apresentar indicadores de validade de construto da versão brasileira do Inventário Espectral de Externalização. MÉTODO: Trata-se de um estudo psicométrico de orientação correlacional. Foram utilizadas duas técnicas clássicas de representação de construto: análise exploratória de fatores comuns e análise de consistência interna. A amostra consistiu de 258 participantes de ambos os sexos, provenientes de diferentes cursos universitários de duas instituições públicas do estado de Minas Gerais. RESULTADOS: A análise fatorial resultou em um modelo de um fator de segunda ordem (Externalização) com três fatores de primeira ordem (dimensões de agressão, de uso de substância e de impulsividade/alienação). Os coeficientes alfa mostraram-se bastante elevados, com índices acima de 0,9 tanto para os três fatores de primeira ordem quanto para o fator geral. CONCLUSÃO: Combinados, os resultados trazem evidências de validade e de fidedignidade para a versão brasileira do Inventário Espectral de Externalização no que tange à sua aplicabilidade a estudantes universitários

The utility of the SCAS-C/P to detect specific anxiety disorders among clinically anxious children

Questionnaire measures offer a time and cost-effective alternative to full diagnostic assessments for identifying and differentiating between potential anxiety disorders and are commonly used in clinical practice. Little is known, however, about the capacity of questionnaire measures to detect specific anxiety disorders in clinically anxious preadolescent children. This study aimed to establish the ability of the Spence Children’s Anxiety Scale (SCAS) subscales to identify children with specific anxiety disorders in a large clinic-referred sample (N = 1,438) of children aged 7 to 12 years. We examined the capacity of the Separation Anxiety, Social Phobia, Generalized Anxiety, and Physical Injury Fears (phobias) subscales to discriminate between children with and without the target disorder. We also identified optimal cutoff scores on subscales for accurate identification of children with the corresponding disorder, and examined the contribution of child, mother, and father reports. The Separation Anxiety subscale was able to accurately identify children with separation anxiety disorder, and this was replicated across all 3 reporters. Mother- and father-reported Social Phobia subscales also accurately identified children with social anxiety disorder, although child report was only able to accurately detect social anxiety disorder in girls. Using 2 or more reporters improved the sensitivity of the Separation Anxiety and Social Phobia subscales but reduced specificity. The Generalized Anxiety and Physical Injury Fears subscales failed to accurately identify children with the corresponding disorders. These findings have implications for the potential use of mother-, father-, and child-report SCAS subscales to detect specific disorders in preadolescent children in clinical settings

Safeguarding adolescent mental health in India (SAMA): study protocol for codesign and feasibility study of a school systems intervention targeting adolescent anxiety and depression in India.

INTRODUCTION: Symptoms of anxiety and depression in Indian adolescents are common. Schools can be opportune sites for delivery of mental health interventions. India, however, is without a evidence-based and integrated whole-school mental health approach. This article describes the study design for the safeguarding adolescent mental health in India (SAMA) project. The aim of SAMA is to codesign and feasibility test a suite of multicomponent interventions for mental health across the intersecting systems of adolescents, schools, families and their local communities in India. METHODS AND ANALYSIS: Our project will codesign and feasibility test four interventions to run in parallel in eight schools (three assigned to waitlist) in Bengaluru and Kolar in Karnataka, India. The primary aim is to reduce the prevalence of adolescent anxiety and depression. Codesign of interventions will build on existing evidence and resources. Interventions for adolescents at school will be universal, incorporating curriculum and social components. Interventions for parents and teachers will target mental health literacy, and also for teachers, training in positive behaviour practices. Intervention in the school community will target school climate to improve student mental health literacy and care. Intervention for the wider community will be via adolescent-led films and social media. We will generate intervention cost estimates, test outcome measures and identify pathways to increase policy action on the evidence. ETHICS AND DISSEMINATION: Ethical approval has been granted by the National Institute of Mental Health Neurosciences Research Ethics Committee (NIMHANS/26th IEC (Behv Sc Div/2020/2021)) and the University of Leeds School of Psychology Research Ethics Committee (PSYC-221). Certain data will be available on a data sharing site. Findings will be disseminated via peer-reviewed journals and conferences

The impact of treatment delivery format on response to Cognitive Behaviour Therapy for pre-adolescent children with anxiety disorders

Background. Several delivery formats of Cognitive Behaviour Therapy (CBT) for child anxiety have been proposed, however there is little consensus on the optimal delivery format. The primary goal of this study was to investigate the impact of the child’s primary anxiety diagnosis on changes in clinical severity (of the primary problem) during individual CBT, group CBT, and guided parent-led CBT. The secondary goal was to investigate the impact of the child’s primary anxiety diagnosis on rates of remission for the three treatment formats. Methods. A sample of 1253 children (5 – 12 years; Mage = 9.3, SD = 1.7) was pooled from CBT trials carried out at 10 sites. Children had a primary diagnosis of Generalised Anxiety Disorder (GAD), Social Anxiety Disorder (SoAD), Specific Phobia (SP) or Separation Anxiety Disorder (SAD). Children and parents completed a semi-structured clinical interview to assess the presence and severity of DSM-IV psychiatric disorders at pre intervention, post intervention and follow-up. Linear mixture modelling was used to evaluate the primary research question and logistic modelling was used to investigate the secondary research question. Results. Children with a primary diagnosis of GAD, SoAD and SAD demonstrated comparable improvements in clinical severity to all three CBT treatment formats. However, children with primary SP showed significantly larger reductions in clinical severity following individual CBT compared to group CBT and guided parent-led CBT. The results were mirrored in the analysis of remission responses with the exception that individual CBT was no longer superior to group CBT for children with a primary SP. Furthermore, the difference between individual and group was not significant when the follow-up data was examined separately. Conclusions. The data show that there may be greater clinical benefit by allocating children with a primary SP to individual CBT, although future research on cost-effectiveness is needed to determine whether the additional clinical benefits justify the additional resources required

Clinical predictors of response to cognitive-behavioral therapy in pediatric anxiety disorders: the genes for treatment (GxT) study.

OBJECTIVE The Genes for Treatment study is an international, multisite collaboration exploring the role of genetic, demographic, and clinical predictors in response to cognitive-behavioral therapy (CBT) in pediatric anxiety disorders. The current article, the first from the study, examined demographic and clinical predictors of response to CBT. We hypothesized that the child's gender, type of anxiety disorder, initial severity and comorbidity, and parents' psychopathology would significantly predict outcome. METHOD A sample of 1,519 children 5 to 18 years of age with a primary anxiety diagnosis received CBT across 11 sites. Outcome was defined as response (change in diagnostic severity) and remission (absence of the primary diagnosis) at each time point (posttreatment, 3-, 6-, and/or 12-month follow-up) and analyzed using linear and logistic mixed models. Separate analyses were conducted using data from posttreatment and follow-up assessments to explore the relative importance of predictors at these time points. RESULTS Individuals with social anxiety disorder (SoAD) had significantly poorer outcomes (poorer response and lower rates of remission) than those with generalized anxiety disorder (GAD). Although individuals with specific phobia (SP) also had poorer outcomes than those with GAD at posttreatment, these differences were not maintained at follow-up. Both comorbid mood and externalizing disorders significantly predicted poorer outcomes at posttreatment and follow-up, whereas self-reported parental psychopathology had little effect on posttreatment outcomes but significantly predicted response (although not remission) at follow-up. CONCLUSION SoAD, nonanxiety comorbidity, and parental psychopathology were associated with poorer outcomes after CBT. The results highlight the need for enhanced treatments for children at risk for poorer outcomes

Genome-wide association study of response to cognitive-behavioural therapy in children with anxiety disorders

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts

Population genomics of sub-Saharan Drosophila melanogaster: African diversity and non-African admixture

(ABRIDGED) We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa FST were found to be enriched in genomic regions of locally elevated cosmopolitan admixture, possibly reflecting a role for some of these loci in driving the introgression of non-African alleles into African populations

Meta-Analysis of Gene Level Tests for Rare Variant Association

The vast majority of connections between complex disease and common genetic variants were identified through meta-analysis, a powerful approach that enables large sample sizes while protecting against common artifacts due to population structure, repeated small sample analyses, and/or limitations with sharing individual level data. As the focus of genetic association studies shifts to rare variants, genes and other functional units are becoming the unit of analysis. Here, we propose and evaluate new approaches for performing meta-analysis of rare variant association tests, including burden tests, weighted burden tests, variable threshold tests and tests that allow variants with opposite effects to be grouped together. We show that our approach retains useful features of single variant meta-analytic approaches and demonstrate its utility in a study of blood lipid levels in ∼18,500 individuals genotyped with exome arrays