Reducing Stress and Preventing Depression (RESPOND): Randomized Controlled Trial of Web-Based Rumination-Focused Cognitive Behavioral Therapy for High-Ruminating University Students

This is the final version. Available from JMIR Publications via the DOI in this record.BACKGROUND: Prevention of depression is a priority to reduce its global disease burden. Targeting specific risk factors, such as rumination, may improve prevention. Rumination-focused Cognitive Behavioral Therapy (RFCBT) was developed to specifically target depressive rumination. OBJECTIVE: The primary objective of this study was to test whether guided Web-based RFCBT (i-RFCBT) would prevent the incidence of major depression relative to usual care in UK university students. The secondary objective was to test the feasibility and estimated effect sizes of unguided i-RFCBT. METHODS: To address the primary objective, a phase III randomized controlled trial was designed and powered to compare high risk university students (N=235), selected with elevated worry/rumination, recruited via an open access website in response to circulars within universities and internet advertisements, randomized to receive either guided i-RFCBT (interactive Web-based RFCBT, supported by asynchronous written Web-based support from qualified therapists) or usual care control. To address the secondary objective, participants were also randomized to an adjunct arm of unguided (self-administered) i-RFCBT. The primary outcome was the onset of a major depressive episode over 15 months, assessed with structured diagnostic interviews at 3 (postintervention), 6, and 15 months post randomization, conducted by telephone, blind to the condition. Secondary outcomes of symptoms of depression and anxiety and levels of worry and rumination were self-assessed through questionnaires at baseline and the same follow-up intervals. RESULTS: Participants were randomized to guided i-RFCBT (n=82), unguided i-RFCBT (n=76), or usual care (n=77). Guided i-RFCBT reduced the risk of depression by 34% relative to usual care (hazard ratio [HR] 0.66, 95% CI 0.35 to 1.25; P=.20). Participants with higher levels of baseline stress benefited most from the intervention (HR 0.43, 95% CI 0.21 to 0.87; P=.02). Significant improvements in rumination, worry, and depressive symptoms were found in the short-to-medium term. Of the 6 modules, guided participants completed a mean of 3.46 modules (SD 2.25), with 46% (38/82) being compliant (completing ≥4 modules). Similar effect sizes and compliance rates were found for unguided i-RFCBT. CONCLUSIONS: Guided i-RFCBT can reduce the onset of depression in high-risk young people reporting high levels of worry/rumination and stress. The feasibility study argues for formally testing unguided i-RFCBT for prevention: if the observed effect sizes are robustly replicated in a phase III trial, it has potential as a scalable prevention intervention. TRIAL REGISTRATION: ISRCTN Registry ISRCTN12683436; https://www.isrctn.com/ISRCTN12683436 (Archived by WebCite at http://www.webcitation.org/77fqycyBX). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-015-1128-9.Wellcome Trus

The Academic Outcomes of Working Memory and Metacognitive Strategy Training in Children: A Double-Blind Randomised Controlled Trial

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Working memory training has been shown to improve performance on untrained working memory tasks in typically developing children, at least when compared to nonadaptive training; however, there is little evidence that it improves academic outcomes. The lack of transfer to academic outcomes may be because children are only learning skills and strategies in a very narrow context, which they are unable to apply to other tasks. Metacognitive strategy interventions, which promote metacognitive awareness and teach children general strategies that can be used on a variety of tasks, may be a crucial missing link in this regard. In this double-blind randomised controlled trial, 95 typically developing children aged 9-14 years were allocated to three cognitive training programmes that were conducted daily after-school. One group received Cogmed working memory training, another group received concurrent Cogmed and metacognitive strategy training, and the control group received adaptive visual search training, which better controls for expectancy and motivation than non-adaptive training. Children were assessed on four working memory tasks, reading comprehension, and mathematical reasoning before, immediately after, and three months after training. Working memory training improved working memory and mathematical reasoning relative to the control group. The improvements in working memory were maintained three months later and these were significantly greater for the group that received metacognitive strategy training, compared to working memory training alone. Working memory training is a potentially effective educational intervention when provided in addition to school; however, future research will need to investigate ways to maintain academic improvements long-term and to optimise metacognitive strategy training to promote fartransfer.Economic and Social Research Council (ESRC

Childhood obesity: Evidence for distinct early and late environmental determinants a 12-year longitudinal cohort study (EarlyBird 62)

Background/objective:The prevalence of childhood obesity continues to rise in most countries, but the exposures responsible remain unclear. The shape of the body mass index (BMI) distribution curve defines how a population responds, and can be described by its three parameters-skew (L), median (M) and variance (S). We used LMS analysis to explore differences in the BMI trajectories of contemporary UK children with those of 25 years ago, and to draw inferences on the exposures responsible.Subjects/methods:We applied Cole's LMS method to compare the BMI trajectories of 307 UK children (EarlyBird cohort) measured annually from 5-16 years (2000-2012) with those of the BMI data set used to construct the UK 1990 growth centiles, and used group-based trajectory modelling (GBTM) to establish whether categorical trajectories emerged.Results:Gender-specific birth weights were normally distributed and similar between both data sets. The skew and variance established by 5 years in the 1990 children remained stable during the remainder of their childhood, but the pattern was different for children 25 years on. The skew at 5 years among the EarlyBird children was greatly exaggerated, and involved selectively the offspring of obese parents, but returned to 1990 levels by puberty. As the skew diminished, so the variance in BMI rose sharply. The median BMI of the EarlyBird children differed little from that of 1990 before puberty, but diverged from it as the variance rose. GBTM uncovered four groups with distinct trajectories, which were related to parental obesity.Conclusions:There appear to be two distinct environmental interactions with body mass among contemporary children, the one operating selectively according to parental BMI during early childhood, the second more generally in puberty.Bright Future TrustBUPA FoundationPeninsula FoundationKirby Laing TrustEarlyBird Diabetes Trus

Physical activity attenuates the mid-adolescent peak in insulin resistance but by late adolescence the effect is lost: a longitudinal study with annual measures from 9–16 years (EarlyBird 66)

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this recordthere is another ORE record for this publication: http://hdl.handle.net/10871/18754Aims/hypothesis: The aim of this work was to test whether the mid-adolescent peak in insulin resistance (IR) and trends in other metabolic markers are influenced by long-term exposure to physical activity. Methods: Physical activity (7 day ActiGraph accelerometry), HOMA-IR and other metabolic markers (glucose, fasting insulin, HbA1c, lipids and BP) were measured annually from age 9 years to 16 years in 300 children (151 boys) from the EarlyBird study in Plymouth, UK. The activity level of each child was characterised, with 95% reliability, by averaging their eight annual physical activity measures. Age-related trends in IR and metabolic health were analysed by multi-level modelling, with physical activity as the exposure measure (categorical and continuous) and body fat percentage (assessed by dual-energy X-ray absorptiometry) and pubertal status (according to age at peak height velocity and Tanner stage) as covariates. Results: The peak in IR at age 12–13 years was 17% lower (p < 0.001) in the more active adolescents independently of body fat percentage and pubertal status. However, this difference diminished progressively over the next 3 years and had disappeared completely by the age of 16 years (e.g. difference was −14% at 14 years, −8% at 15 years and +1% at 16 years; ‘physical activity × age2’ interaction, p < 0.01). Triacylglycerol levels in girls (−9.7%, p = 0.05) and diastolic blood pressure in boys (−1.20 mmHg, p = 0.03) tended to be lower throughout adolescence in the more active group. Conclusions/interpretation: Our finding that physical activity attenuates IR during mid-adolescence may be clinically important. It remains to be established whether the temporary attenuation in IR during this period has implications for the development of diabetes in adolescence and for future metabolic health generally.The EarlyBird study (BSM, JH, MM, ANJ, LDV, TJW) was supported by the Bright Future Trust, the Kirby Laing Foundation, the Peninsula Foundation and the EarlyBird Diabetes Trust. WEH was supported by the National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

Implementing multifactorial psychotherapy research in online virtual environments (IMPROVE-2): study protocol for a phase III trial of the MOST randomized component selection method for internet cognitive-behavioural therapy for depression.

BACKGROUND: Depression is a global health challenge. Although there are effective psychological and pharmaceutical interventions, our best treatments achieve remission rates less than 1/3 and limited sustained recovery. Underpinning this efficacy gap is limited understanding of how complex psychological interventions for depression work. Recent reviews have argued that the active ingredients of therapy need to be identified so that therapy can be made briefer, more potent, and to improve scalability. This in turn requires the use of rigorous study designs that test the presence or absence of individual therapeutic elements, rather than standard comparative randomised controlled trials. One such approach is the Multiphase Optimization Strategy, which uses efficient experimentation such as factorial designs to identify active factors in complex interventions. This approach has been successfully applied to behavioural health but not yet to mental health interventions. METHODS/DESIGN: A Phase III randomised, single-blind balanced fractional factorial trial, based in England and conducted on the internet, randomized at the level of the patient, will investigate the active ingredients of internet cognitive-behavioural therapy (CBT) for depression. Adults with depression (operationalized as PHQ-9 score ≥ 10), recruited directly from the internet and from an UK National Health Service Improving Access to Psychological Therapies service, will be randomized across seven experimental factors, each reflecting the presence versus absence of specific treatment components (activity scheduling, functional analysis, thought challenging, relaxation, concreteness training, absorption, self-compassion training) using a 32-condition balanced fractional factorial design (2IV(7-2)). The primary outcome is symptoms of depression (PHQ-9) at 12 weeks. Secondary outcomes include symptoms of anxiety and process measures related to hypothesized mechanisms. DISCUSSION: Better understanding of the active ingredients of efficacious therapies, such as CBT, is necessary in order to improve and further disseminate these interventions. This study is the first application of a component selection experiment to psychological interventions in depression and will enable us to determine the main effect of each treatment component and its relative efficacy, and cast light on underlying mechanisms, so that we can systematically enhance internet CBT. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24117387 . Registered 26 August 2014.Funding for this trial is provided by grants from the Cornwall NHS Foundation Trust and South West Peninsula Academic Health Research Network to EW. LC is supported by United States National Institutes of Health grants P50DA039838, P01CA180945, R01DK097364, and R01AA022931

Psychological therapy for mood instability within bipolar spectrum disorder: a single-arm feasibility study of a dialectical behaviour therapy-informed approach

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The datasets generated and analysed during the current study are not publicly available to protect participant confidentiality, but are available from the corresponding author on reasonable request, subject to any applicable regulatory approvals for secondary use of the data.Background: We sought to evaluate the acceptability of a psychological therapy programme (Therapy for Inter-episode Mood Variability in Bipolar Disorder (ThrIVe-B)) for individuals with ongoing bipolar mood instability and the feasibility and acceptability of potential trial procedures. We also evaluated the performance of clinical and process outcome measures and the extent to which the programme potentially represents a safe and effective intervention. Method: We conducted an open (uncontrolled) trial in which 12 individuals with a bipolar spectrum diagnosis commenced the ThrIVe-B programme after completing baseline assessments. The programme comprised 16 group skills training sessions plus individual sessions and a supporting smartphone application. Follow-up assessments were at therapy end-point and 6 months post-treatment. Results: Nine participants completed treatment. Ten provided end-of-treatment data; of these, nine were satisfied with treatment. Interviews with participants and clinicians indicated that the treatment was broadly feasible and acceptable, with suggestions for improvements to content, delivery and study procedures. Exploration of change in symptoms was consistent with the potential for the intervention to represent a safe and effective intervention. Conclusions: Conducting further evaluation of this approach in similar settings is likely to be feasible, whilst patient reports and the pattern of clinical change observed suggest this approach holds promise for this patient group. Future research should include more than one study site and a comparison arm to address additional uncertainties prior to a definitive trial. Trial registration: Trial Registration: ClinicalTrials.gov NCT02637401; registered 22.12.15 (retrospectively registered)

Physical activity attenuates the mid-adolescent peak in insulin resistance but by late adolescence the effect is lost: a longitudinal study with annual measures from 9-16 years (EarlyBird 66)

The final publication is available at Springer via http://dx.doi.org/10.1007/s00125-015-3714-5There is another ORE record for this publication: http://hdl.handle.net/10871/34546AIMS/HYPOTHESIS: The aim of this work was to test whether the mid-adolescent peak in insulin resistance (IR) and trends in other metabolic markers are influenced by long-term exposure to physical activity. METHODS: Physical activity (7 day ActiGraph accelerometry), HOMA-IR and other metabolic markers (glucose, fasting insulin, HbA1c, lipids and BP) were measured annually from age 9 years to 16 years in 300 children (151 boys) from the EarlyBird study in Plymouth, UK. The activity level of each child was characterised, with 95% reliability, by averaging their eight annual physical activity measures. Age-related trends in IR and metabolic health were analysed by multi-level modelling, with physical activity as the exposure measure (categorical and continuous) and body fat percentage (assessed by dual-energy X-ray absorptiometry) and pubertal status (according to age at peak height velocity and Tanner stage) as covariates. RESULTS: The peak in IR at age 12-13 years was 17% lower (p < 0.001) in the more active adolescents independently of body fat percentage and pubertal status. However, this difference diminished progressively over the next 3 years and had disappeared completely by the age of 16 years (e.g. difference was -14% at 14 years, -8% at 15 years and +1% at 16 years; 'physical activity × age(2)' interaction, p < 0.01). Triacylglycerol levels in girls (-9.7%, p = 0.05) and diastolic blood pressure in boys (-1.20 mmHg, p = 0.03) tended to be lower throughout adolescence in the more active group. CONCLUSIONS/INTERPRETATION: Our finding that physical activity attenuates IR during mid-adolescence may be clinically important. It remains to be established whether the temporary attenuation in IR during this period has implications for the development of diabetes in adolescence and for future metabolic health generally.Bright Future TrustKirby Laing FoundationPeninsula FoundationEarlyBird Diabetes TrustNational Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care (CLAHRC

Investigation of active ingredients within internet cognitive-behavioral therapy for depression: a randomized optimization trial

This is the author accepted manuscript. The final version is available from the American Medical Association via the DOI in this recordIMPORTANCE: There is limited understanding of how complex evidence-based psychological interventions such as cognitive behavioral therapy (CBT) for depression work. Identifying active ingredients may help to make therapy more potent, brief, and scalable. OBJECTIVE: To test the individual main effects and interactions of 7 treatment components within internet-delivered CBT for depression to investigate its active ingredients. DESIGN, SETTING, AND PARTICIPANTS: This randomized optimization trial using a 32-condition, balanced, fractional factorial optimization experiment (IMPROVE-2) recruited adults with depression (Patient Health Questionnaire-9 [PHQ-9] score ≥10) from internet advertising and the UK National Health Service Improving Access to Psychological Therapies service. Participants were randomized from July 7, 2015, to March 29, 2017, with follow-up for 6 months after treatment until December 29, 2017. Data were analyzed from July 2018 to April 2023. INTERVENTIONS: Participants were randomized with equal probability to 7 experimental factors within the internet CBT platform, each reflecting the presence vs absence of specific treatment components (activity scheduling, functional analysis, thought challenging, relaxation, concreteness training, absorption, and self-compassion training). MAIN OUTCOMES AND MEASURES: The primary outcome was depression symptoms (PHQ-9 score). Secondary outcomes include anxiety symptoms and work, home, and social functioning. RESULTS: Among 767 participants (mean age [SD] age, 38.5 [11.62] years; range, 18-76 years; 635 women [82.8%]), 506 (66%) completed the 6-month posttreatment follow-up. On average, participants receiving internet-delivered CBT had reduced depression (pre-to-posttreatment difference in PHQ-9 score, -7.79 [90% CI, -8.21 to -7.37]; 6-month follow-up difference in PHQ-9 score, -8.63 [90% CI, -9.04 to -8.22]). A baseline score-adjusted analysis of covariance model using effect-coded intervention variables (-1 or +1) found no main effect on depression symptoms for the presence vs absence of activity scheduling, functional analysis, thought challenging, relaxation, concreteness training, or self-compassion training (posttreatment: largest difference in PHQ-9 score [functional analysis], -0.09 [90% CI, -0.56 to 0.39]; 6-month follow-up: largest difference in PHQ-9 score [relaxation], -0.18 [90% CI, -0.61 to 0.25]). Only absorption training had a significant main effect on depressive symptoms at 6-month follow-up (posttreatment difference in PHQ-9 score, 0.21 [90% CI, -0.27 to 0.68]; 6-month follow-up difference in PHQ-9 score, -0.54, [90% CI, -0.97 to -0.11]). CONCLUSIONS AND RELEVANCE: In this randomized optimization trial, all components of internet-delivered CBT except absorption training did not significantly reduce depression symptoms relative to their absence despite an overall average reduction in symptoms. The findings suggest that treatment benefit from internet-delivered CBT probably accrues from spontaneous remission, factors common to all CBT components (eg, structure, making active plans), and nonspecific therapy factors (eg, positive expectancy), with the possible exception of absorption focused on enhancing direct contact with positive reinforcers. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN24117387.Cornwall Partnership NHS Foundation TrustSouth West Academic Health Science Networ

Working memory updating training reduces state repetitive negative thinking: proof-of-concept for a novel cognitive control training (article)

This is the final version. Available on open access from Elsevier via the DOI in this record.The research data supporting this publication are openly available from the University of Exeter's institutional repository at https://doi.org/10.24378/exe.3283Repetitive negative thinking (RNT) is a proximal risk factor implicated in the onset and maintenance of common mental health problems such as depression and anxiety. Adolescence may be a key developmental window in which to target RNT and prevent the emergence of such disorders. Impairments in updating the contents of working memory are hypothesised to causally contribute to RNT, and some theorists have suggested these difficulties may be specific to the manipulation of negative information. The present study compared the effects of computerised adaptive working memory updating training (in which the task becomes more difficult as performance improves) to a non-adaptive control task in reducing levels of RNT. 124 healthy young people were randomised to 20 sessions of (i) working memory updating training using neutral stimuli, (ii) working memory updating training using negative stimuli, or (iii) non-adaptive working memory updating training. Adaptive working memory updating training using neutral, but not negative, stimuli resulted in significant improvements to working memory updating for negative material, as assessed using an unpractised task, and significant reductions in susceptibility to state RNT. These findings demonstrate proof-of-concept that working memory updating training has the potential to reduce susceptibility to episodes of state RNT.Wellcome Trus

Adapted Behavioural Activation for Bipolar Depression: A Randomised Multiple Baseline Case Series

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: The data presented in this study are available on request from the corresponding author provided that suitable approvals are in place and the data can be shared anonymously. The data are not publicly available due to the need to preserve the anonymity of participants.Behavioural Activation (BA) is associated with a substantial evidence base for treatment of acute unipolar depression, and has promise as an easily disseminable psychological intervention for bipolar depression. Using a randomised multiple baseline case series design we examined the feasibility and acceptability of an adapted version of BA in a U.K. outpatient sample of 12 adults with acute bipolar depression. Participants were allocated at random to a 3–8 week wait period before being offered up to 20 sessions of BA. They completed outcome measures at intake, pre- and post-treatment and weekly symptom measures across the study period. Retention in therapy was high (11/12 participants completed the target minimum number of sessions), and all participants returning acceptability measures reported high levels of satisfaction with the intervention. No therapy-related serious adverse events were reported, nor were there exacerbations in manic symptoms that were judged to be a result of the intervention. The pattern of change on outcome measures is consistent with the potential for clinical benefit; six of the nine participants with a stable baseline showed clinically significant improvement on the primary outcome measure. The findings suggest adapted BA for bipolar depression is a feasible and acceptable approach that merits further investigation