The development and evaluation of an online Behavioural Activation programme for the treatment of low mood and depression in adolescents

Background: Depression is a major health concern, with an estimated prevalence of 2% in UK adolescents. Behavioural Activation (BA), a psychological therapy that is simple and can be delivered by a wide variety of clinicians has demonstrated effectiveness in the treatment of adults. However less research has examined its application with young people. Receiving timely and effective treatments is essential for recovery and prevention of recurrence but can be impeded by both individual and service-related barriers. Evidence from systematic reviews and meta-analyses suggests that delivering interventions in an online format may circumvent these barriers. This research aimed to develop and evaluate an online BA programme for adolescents with low mood and/or depression. Methods: Aligning to important phases of co-design in intervention development, this work encompasses stages of assessment, development, and evaluation. The findings from a systematic review and meta-analysis and qualitative work with young people and healthcare professionals informed the development of a new online BA intervention (BALM). The intervention’s acceptability was examined in a non-randomised feasibility study. Results: Through consolidating and synthesising the findings from the assessment stages of this thesis whilst considering the biopsychosocial development of adolescents, a ten-session online BA programme (BALM) was developed. An initial evaluation of BALM with 12 adolescents experiencing low mood and/or depression demonstrated it is feasible to recruit to a treatment of this type. However, whilst several therapy components were deemed acceptable, low adherence and high dropout highlighted the modifications required both to BALM and the delivery of future, similar research. Conclusions: This thesis has provided additional support to considering BA as an alternative treatment option for adolescents experiencing low mood and/or depression notwithstanding the need to carefully consider measures to support engagement and adherence. Online delivery may help to address the multifaceted barriers faced by adolescents when accessing timely support

Computerised cognitive-behavioural therapy for depression in adolescents : feasibility results and 4-month outcomes of a UK randomised controlled trial

OBJECTIVES: Computer-administered cognitive-behavioural therapy (CCBT) may be a promising treatment for adolescents with depression, particularly due to its increased availability and accessibility. The feasibility of delivering a randomised controlled trial (RCT) comparing a CCBT program (Stressbusters) with an attention control (self-help websites) for adolescent depression was evaluated. DESIGN: Single centre RCT feasibility study. SETTING: The trial was run within community and clinical settings in York, UK. PARTICIPANTS: Adolescents (aged 12-18) with low mood/depression were assessed for eligibility, 91 of whom met the inclusion criteria and were consented and randomised to Stressbusters (n=45) or websites (n=46) using remote computerised single allocation. Those with comorbid physical illness were included but those with psychosis, active suicidality or postnatal depression were not. INTERVENTIONS: An eight-session CCBT program (Stressbusters) designed for use with adolescents with low mood/depression was compared with an attention control (accessing low mood self-help websites). PRIMARY AND SECONDARY OUTCOME MEASURES: Participants completed mood and quality of life measures and a service Use Questionnaire throughout completion of the trial and 4 months post intervention. Measures included the Beck Depression Inventory (BDI) (primary outcome measure), Mood and Feelings Questionnaire (MFQ), Spence Children's Anxiety Scale (SCAS), the EuroQol five dimensions questionnaire (youth) (EQ-5D-Y) and Health Utility Index Mark 2 (HUI-2). Changes in self-reported measures and completion rates were assessed by treatment group. RESULTS: From baseline to 4 months post intervention, BDI scores and MFQ scores decreased for the Stressbusters group but increased in the website group. Quality of life, as measured by the EQ-5D-Y, increased for both groups while costs at 4 months were similar to baseline. Good feasibility outcomes were found, suggesting the trial process to be feasible and acceptable for adolescents with depression. CONCLUSIONS: With modifications, a fully powered RCT is achievable to investigate a promising treatment for adolescent depression in a climate where child mental health service resources are limited. TRIAL REGISTRATION NUMBER: ISRCTN31219579

Cross-culturally adapted psychological interventions for the treatment of depression and/or anxiety among young people: A scoping review

Background: Mental health problems among young people are a major global public health challenge. Psychological interventions may improve mental health, yet most are developed in western cultures, and it is unclear whether they are applicable to other geographical settings and can be delivered successfully to diverse populations. We identified empirical studies focusing upon cross-culturally adapted psychological interventions and examined the cultural adaptation process used and the effectiveness of the interventions in the treatment of depression and/or anxiety disorders among young people (defined here as children and adolescents aged between 8-18 years). Method: We conducted a scoping review aligning to the guidelines reported in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) Statement. Stakeholder engagement enabled us to discuss the findings of the review and obtain feedback. Results: We identified 17 studies of cross-culturally adapted psychological interventions that considered the appropriate language, metaphors, culturally appropriate terms, and cultural values of young people. Most studies (n = 11) adopted a randomised control trial (RCT) methodology. Six studies used the ecological validity and cultural sensitivity framework. Planned adaptation, cultural adaptation of content, and surface and deep structure level adaptations were used in other studies. Apart from one pilot study, all studies reported that culturally adapted interventions resulted in improvements in depression and/or anxiety symptoms in young people. The results suggest the potential effectiveness of cross-culturally adapted interventions within this context. Our stakeholder consultations demonstrated that engaging different community-level stakeholders in the adaptation process was highly recommended. Conclusions: Whilst most included studies indicated improvements in depression and/or anxiety symptoms in young people following a cross-culturally adapted intervention, more work is needed in this area. In particular, focus should be placed upon identifying the dimensions of interventions that should be culturally adapted to make them acceptable, engaging and effective

The alleviating specific phobias in children trial : Challenges and solutions to implementing a randomized controlled trial in clinical services

In 2015, The Alleviating Specific Phobias Experienced by Children Trial (ASPECT) was commissioned by the National Institute for Health and Care Research (NIHR) to compare the clinical and cost-effectiveness of multi-session Cognitive Behavioral Therapy (CBT) for specific phobias in children and young people (CYP) (aged 7–16), with a briefer variant called One Session Treatment (OST). From 2016 to 2020, ASPECT recruited n = 274 CYP with specific phobias and their families from across England, including 26 Child and Adolescent Mental Health Services (CAMHS) centres, three voluntary sector centers and one University-based wellbeing service. Whilst the trial successfully reached its recruitment target, the challenges experienced in its delivery highlight the difficulties of embedding child and adolescent research into clinical settings and routine practice. Using ASPECT as a case in point, this paper explores these challenges and provides important insights and considerations of potential benefit to others conducting research within the field of child and adolescent mental health

Clinical and cost-effectiveness of one-session treatment (OST) versus multisession cognitive-behavioural therapy (CBT) for specific phobias in children : protocol for a non-inferiority randomised controlled trial

INTRODUCTION: Specific phobias (intense, enduring fears of an object or situation that lead to avoidance and severe distress) are highly prevalent among children and young people. Cognitive-behavioural therapy (CBT) is a well-established, effective intervention, but it can be time consuming and costly because it is routinely delivered over multiple sessions during several months. Alternative methods of treating severe and debilitating phobias in children are needed, like one-session treatment (OST), to reduce time and cost, and to prevent therapeutic drift and help children recover quickly. Our study explores whether (1) outcomes with OST are 'no worse' than outcomes with multisession CBT, (2) OST is acceptable to children, their parents and the practitioners who use it and (3) OST offers good value for money to the National Health Service (NHS) and to society. METHOD: A pragmatic, non-inferiority, randomised controlled trial will compare OST with multisession CBT-based therapy on their clinical and cost-effectiveness. The primary clinical outcome is a standardised behavioural task of approaching the feared stimulus at 6 months postrandomisation. The outcomes for the within-trial cost-effectiveness analysis are quality-adjusted life years based on EQ-5D-Y, and individual-level costs based of the intervention and use of health and social service care. A nested qualitative evaluation will explore children's, parents' and practitioners' perceptions and experiences of OST. A total of 286 children, 7-16 years old, with DSM-IV diagnoses of specific phobia will be recruited via gatekeepers in the NHS, schools and voluntary youth services, and via public adverts. ETHICS AND DISSEMINATION: The trial received ethical approval from North East and York Research Ethics Committee (Reference: 17/NE/0012). Dissemination plans include publications in peer-reviewed journals, presentations in relevant research conferences, local research symposia and seminars for children and their families, and for professionals and service managers. TRIAL REGISTRATION NUMBER: ISRCTN19883421;Pre-results

One-session treatment compared with multisession CBT in children aged 7-16 years with specific phobias : the ASPECT non-inferiority RCT

BACKGROUND: Up to 10% of children and young people have a specific phobia that can significantly affect their mental health, development and daily functioning. Cognitive-behavioural therapy-based interventions remain the dominant treatment, but limitations to their provision warrant investigation into low-intensity alternatives. One-session treatment is one such alternative that shares cognitive-behavioural therapy principles but has a shorter treatment period. OBJECTIVE: This research investigated the non-inferiority of one-session treatment to cognitive-behavioural therapy for treating specific phobias in children and young people. The acceptability and cost-effectiveness of one-session treatment were examined. DESIGN: A pragmatic, multicentre, non-inferiority randomised controlled trial, with embedded economic and qualitative evaluations. SETTINGS: There were 26 sites, including 12 NHS trusts. PARTICIPANTS: Participants were aged 7-16 years and had a specific phobia defined in accordance with established international clinical criteria. INTERVENTIONS: Participants were randomised 1 : 1 to receive one-session treatment or usual-care cognitive-behavioural therapy, and were stratified according to age and phobia severity. Outcome assessors remained blind to treatment allocation. MAIN OUTCOME MEASURES: The primary outcome measure was the Behavioural Avoidance Task at 6 months' follow-up. Secondary outcomes included the Anxiety Disorder Interview Schedule, Child Anxiety Impact Scale, Revised Children's Anxiety and Depression Scale, a goal-based outcome measure, Child Health Utility 9D, EuroQol-5 Dimensions Youth version and resource usage. Treatment fidelity was assessed using the Cognitive Behaviour Therapy Scale for Children and Young People and the One-Session Treatment Rating Scale. RESULTS: A total of 274 participants were recruited, with 268 participants randomised to one-session treatment ( n  = 134) or cognitive-behavioural therapy ( n  = 134). A total of 197 participants contributed some data, with 149 participants in the intention-to-treat analysis and 113 in the per-protocol analysis. Mean Behavioural Avoidance Task scores at 6 months were similar across treatment groups when both intention-to-treat and per-protocol analyses were applied [cognitive-behavioural therapy: 7.1 (intention to treat), 7.4 (per protocol); one-session treatment: 7.4 (intention to treat), 7.6 (per protocol); on the standardised scale adjusted mean difference for cognitive-behavioural therapy compared with one-session treatment -0.123, 95% confidence interval -0.449 to 0.202 (intention to treat), mean difference -0.204, 95% confidence interval -0.579 to 0.171 (per protocol)]. These findings were wholly below the standardised non-inferiority limit of 0.4, which suggests that one-session treatment is non-inferior to cognitive-behavioural therapy. No between-group differences in secondary outcome measures were found. The health economics evaluation suggested that, compared with cognitive-behavioural therapy, one-session treatment marginally decreased the mean service use costs and maintained similar mean quality-adjusted life-year improvement. Nested qualitative evaluation found one-session treatment to be considered acceptable by those who received it, their parents/guardians and clinicians. No adverse events occurred as a result of phobia treatment. LIMITATIONS: The COVID-19 pandemic meant that 48 children and young people could not complete the primary outcome measure. Service waiting times resulted in some participants not starting therapy before follow-up. CONCLUSIONS: One-session treatment for specific phobia in UK-based child mental health treatment centres is as clinically effective as multisession cognitive-behavioural therapy and highly likely to be cost-saving. Future work could involve improving the implementation of one-session treatment through training and commissioning of improved care pathways. TRIAL REGISTRATION: This trial is registered as ISRCTN19883421. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 42. See the NIHR Journals Library website for further project information

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Is behavioural activation an effective treatment for depression in children and adolescents? An updated systematic review and meta-analysis

Behavioural Activation (BA)—a brief therapy based on the scheduling of enjoyable, purposeful and rewarding activities—is an effective and cost-effective treatment for depression in adults that shows promise for children and adolescents. We provide an update on a previous systematic review of evidence on BA—delivered in-person, telephone, or online—for depression and comorbid anxiety in children and adolescents. We conducted systematic literature searches in 6 databases up to February 2024. We included all study designs evaluating BA with participants up to 18 years old with diagnosable depression, as established by a validated screening tool or diagnostic manual. We used the Moncrieff Scale and the Cochrane Risk of Bias tool to assess study quality. We summarised the findings of all study types with a narrative synthesis and of randomised controlled trials (RCTs) with a meta-analysis. Overall, 24 studies (6 RCTs, 18 pre-post evaluations, n = 2,758) met our inclusion criteria. A meta-analysis of 4 RCTs (n = 156) showed that BA has a small effect of 0.24 (Hedge’s adjusted g) in reducing depression symptoms compared to a waiting-list control, usual care and other therapies. Online and telephone-facilitated BA was shown to be feasible in 3 studies and effective in 1. Outcomes on comorbid anxiety were mixed. No economic evaluations met our inclusion criteria. BA shows sufficient promise as an intervention for reducing depression symptoms in children and adolescents to justify the need for further RCTs, providing that five conditions are met: studies are powered to detect a minimal clinically important difference; BA materials are fit-for-purpose to produce clinically meaningful change; follow-ups are longer than 6 months; primary outcomes are child-reported; and intervention costs, resource use and adverse events are reported