NIHRDataInsights/HRCSData huggingface dataset:
Title: FORWARDS; Facilitating Opiate Recovery: Withdrawal and Abstinence through Detoxification Support.
Funder: Medical Research Council

Abstract: This proposal targets improving the current poor outcomes for opiate detoxification. Based on supportive preclinical and preliminary clinical evidence, we will assess whether the GABA-B agonist, baclofen, can facilitate detoxification from methadone, the most commonly used opiate substitution therapy (OST) in opiate addiction. First, optimal combined doses of baclofen and methadone will be identified that show no safety concerns (study 1). Opiate addicts (DSM-5) on methadone maintenance for over 4 weeks will complete a placebo controlled, single (subject) blind, single ascending dose pharmacokinetic-pharmacodynamic study in a parallel group sequential design. Our planned escalation of baclofen is 10mg-30mg-60mg-90mg, with at least n=8 at each baclofen or placebo dose level in a 3:1 ratio respectively, at a range of methadone doses (<60mg, =/>60mg). Assessments of safety and tolerability include: cardiovascular, respiration, anxiety, sedation, opiate withdrawal, craving, plasma baclofen and growth hormone levels. To proceed with Study 2, at least 30mg baclofen must be safe with a minimum of 60mg/d methadone ie clinically relevant doses. Assuming safety is evident, Study 2 will be a proof-of-concept double-blind randomised placebo-controlled trial to determine if baclofen shows potential efficacy in facilitating detoxification from methadone in community-based opiate addicts. We will include an internal feasibility phase and recruit sufficient opiate addicts (DSM-5) so that 56 complete the trial. The primary outcome is the reduction in methadone dose in baclofen vs placebo within 12 weeks. Secondary outcomes of abstinence, time to abstinence, anxiety, sleep, restless legs, adverse events and feasibility regarding recruitment and retention will be collected. If a clinically meaningful reduction in methadone dose is observed and other measures are positive, we will design a full trial to determine if baclofen can successfully facilitate detoxification from OST.


Research activity codes: 5.1 PHARMACEUTICALS;6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Astrocyte mechanisms in depression
Funder: Medical Research Council

Abstract: While depression is the biggest challenge for mental health care, we still know very little about the biological changes driving it. Here, I propose to investigate how non-neuronal brain cells, astrocytes, contribute to the aetiology of depression and to the therapeutic effect of antidepressants. My preliminary data indicate that reducing lactate specifically in astrocytes in the amygdala augments the stress response in mice. Further preliminary results show that antidepressants fluoxetine and imipramine induce lactate release in vitro. I hypothesise that lactate, mainly produced by astrocytes in the brain, is an essential regulator of emotional behaviour and crucial for the therapeutic effect of antidepressants. To test this hypothesis, I will use an unpredictable chronic mild stress model of depression in combination with lactate biosensors, cell type and brain area specific manipulation of astrocyte-derived lactate and astrocyte-specific RNA sequencing to: 1. Determine whether astrocyte-specific reduction of lactate will aggravate depressive phenotype in mice 2. Demonstrate that reducing astrocyte lactate weakens therapeutic effects of antidepressants 3. Identify downstream signalling pathways mediating the effect of lactate on emotional behaviour and define astrocyte-specific genes and pathways affected by antidepressant treatment. This research will reveal novel molecular mechanisms of depression and will lay the groundwork for the development of a novel class of antidepressant targeting astrocyte signalling pathways.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Non human primate investigations into hippocampal-prefrontal interactions and cognitive dysfunction of relevance to schizophrenia
Funder: Medical Research Council

Abstract: Schizophrenia is a devastating, incurable psychiatric disorder featuring three main symptom clusters: positive symptoms, which are fairly well treated with current antipsychotic drugs, and emotional and cognitive disruptions which are harder to treat and profoundly impact quality of life. Clinical neuroimaging studies, and rodent models of schizophrenia have implicated dysfunction in regions of the prefrontal cortex (PFC) and glutamatergic overactivity within the anterior hippocampus (aHipp) in the mechanisms underlying these cognitive symptoms. In addition, disruption of hippocampal parvalbumin-positive inhibitory GABAergic interneurons, and loss of their extracellular matrix support structure, the perineuronal net (PNN), induce schizophrenia-like changes in rodent models. As the aHipp projects directly to the PFC, we hypothesise that aHipp glutamatergic hyperfunction caused by PNN disruption may induce alterations in PFC function that underlie the cognitive symptoms of schizophrenia, but knowledge of this circuitry is lacking. This proposal will therefore use a novel marmoset monkey model of schizophrenia - PNN degradation - to determine the specific involvement of aHipp-PFC circuitry in some of the cognitive symptoms of schizophrenia. Specifically, we will use microdialysis, 18F-DOPA positron emission tomography (PET), and magnetic resonance spectroscopy to determine how aHipp PNN degradation alters neurochemistry within two PFC regions of a priori interest: the dorsolateral PFC (dlPFC) and the orbitofrontal cortex (OFC). We will also use translational OFC- and dlPFC-dependent cognitive tasks and 18f-fluorodeoxyglucose PET to identify, and compare, how this circuitry contributes to regional activity and behaviour in both model and healthy systems, before administering compounds both focally and systemically to identify new pharmacotherapies better targeted to these disabling symptoms.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Developing & testing the feasibility of a sports-based mental health promotion intervention for adolescents in Nepal: a community engagement approach
Funder: Medical Research Council

Abstract: Mental health promotion interventions that improve mental wellbeing, self-efficacy, self-esteem and emotion regulation, are effective in improving adolescent mental health in LMICs and could be more cost-effective than treatment approaches. We aim to develop and test the feasibility of an intervention that uses sport to promote mental health among adolescents aged 10-19 in Nepal. We selected this type of intervention because there is evidence that sport improves mental health, adolescent participation in sports is supported by Nepalese and global policy, and because of the potential scale and reach through a national network of sports clubs. We are working in Nepal because of its large population of adolescents, and their unmet mental health needs. We will adopt a community engagement approach to intervention development, which seeks to foster respectful relationships between the researchers and the community, and build legitimacy for the research. Our study has seven steps: (1) Consultation with stakeholder groups (adolescents, parents and teachers, and mental health and sports experts) on potential intervention content and research plans (2) Mapping of sports for development programmes in Nepal, and a review of sports-based mental health interventions in LMICs (3) A photovoice study to explore barriers and facilitators to adolescents participating in sports (4) A public funfair using sports and art to mobilise communities on mental health and identify community preferences for a sports-based intervention (5) Theory of change workshops with stakeholder groups to develop the intervention content (6) Validation of tools to measure mental health promotion (7) Intervention feasibility and acceptability testing among 200 adolescent boys and girls Our research will inform a full-scale evaluation of the intervention, whilst expanding global knowledge on sports-based mental health intervention and building a sustainable research platform in Nepal.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Safeguarding adolescent mental health in India: a co-designed feasibility study of a systems intervention targeting youth anxiety and depression.
Funder: Medical Research Council

Abstract: Anxiety and depression in Indian adolescents are common and youth suicides outnumber AIDS-related and maternal deaths combined. Indian secondary schools, which is often harsh and punitive, can present serious risk factors to adolescent mental health. In principle, schools can be mental health promoting for all young people, and for symptomatic young people, early intervention in the form of low-intensity psychoeducation or self-help can prevent escalation of symptoms to levels of clinical disorder. However, India is without a universal school-based mental health approach. Our 36 month project will co-design and feasibility / acceptability test four interventions to run in parallel in 8 schools (3 to waitlist) with the primary aim of reducing the prevalence of adolescent anxiety and depression. Co-design/co-adaptation will build on evidence and resources where available and LMIC relevant, and span content, implementation and evaluation protocols. Interventions will be target evidence-based individual and contextual risk and protective factors for adolescent mental health. Intervention for young people will be a universal (as recommended by previous reviewers), transdiagnostic, psychologically informed mental health curriculum approach. Interventions for parents and teachers will be MHL, and for teachers also training in positive behaviour practices. School climate will be targeted to reduce stigmatising attitudes and improve community MHL. We will target the wider community and sector with MHL campaigning. Based on rules for progression to trial (centering on trial recruitment, protocol adherence and outcome data), we will determine intervention feasibility and acceptability, and (via process measures) what is needed to optimise the intervention. We will generate cost-estimates, identify pathways to increase policy action on the evidence, promote the visibility of young people, and strengthen mental health research capacity in India and the UK.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Community-based psychological treatment for adolescents with anxiety and depression in India
Funder: Medical Research Council

Abstract: India is home to one in five of all adolescents, and an estimated 7-12% of boys and girls aged 10-19 years suffer from mental health problems. The treatment gap for adolescent mental disorders is largely unknown but is likely to be even greater than for adults (>85%). Non-specialist workers employed by India's National Adolescent Health programme do not currently have the tools to screen adolescents for anxiety and depression or training in evidence-based psychological treatments to help them. Our project will aim to answer four research questions: 1 What explanatory models do adolescents, their families and non-specialist workers have for adolescent anxiety and depression in rural and urban settings? 2 What are the most appropriate tools to screen adolescents for anxiety and depression in community settings? 3 How can a stepped care model for anxiety and depression in adolescents be developed, including: (a) a feasible screening approach; (b) an adapted psychological treatment which can be used by community-based non-specialist workers; (c) referral pathways? 4 What are the feasibility, acceptability and cost of this stepped care model for adolescents, their families, and treatment providers? We will conduct qualitative research with adolescents, their relatives, and non-specialist workers in rural Jharkhand (eastern India) and informal urban settlements (slums) of Mumbai to explore how they understand and address symptoms of anxiety and depression. We will seek to validate two existing tools to screen adolescents for anxiety and depression (the Patient Health Questionnaire - Adolescent and the Revised Children's Anxiety and Depression Scale). We will work with adolescents, their families and non-specialist workers to adapt one of five psychological treatments for anxiety and depression so they can be delivered by non-specialists in the community. Finally, we will pilot the screening, psychological treatment and referral system for a period of nine months.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: THEHOPE-Traditional healers working with primary care and mental health for early intervention in psychosis in adolescent:intervention and feasibility
Funder: Medical Research Council

Abstract: First Episode Psychosis (FEP) has peak incidence in adolescent. Most patients consult traditional and spiritual healers (TSH) before seeking professional help in low and middle income countries (LMIC), which is a major factor for the long Duration of Untreated Psychosis (DUP) in these countries. We aim to develop a culturally appropriate and context-bespoke intervention (THEHOPE) for early identification, referral and management of First Episode Psychosis (FEP) in the adolescent population while working collaboratively with traditional healers and primary care physicians (PCPs). THEHOPE is an organizational/service level intervention that will consist of a cascade model of training and task shifting from psychiatrists to PCP and from PCP to traditional healers, and establishing community pathways to promote early identification and management of FEP. The study is located in Peshawar, Khyber Pakhtunkhwa, Pakistan. The research Plan will consist of following four work packages:- 1. Qualitative and ethnographic studies to inform intervention development and training needs and methodology for the TSH and PCPs. 2. UK experts in early psychosis training two local psychiatrists who in turn train 4 PCPs. These PCPs then train 20 TSH in the intervention arm and work collaboratively with them for early detection and referral of FEP in adolescent. The Enhanced Treatment As Usual (ETAU) will be control arm. 3. A cluster feasibility RCT, randomising 92 Union Councils in 1:1 ratio to THEHOPE and ETAU arms. Key feasibility outcomes for definitive trial will include total number of cases referred by TSH and PCP with suspected FEP and likelihood of the confirmed diagnosis of FEP in these cases based on interview by psychiatrist, DUP in those meeting criteria for FEP, the willingness of TSH to work with health services, recruitment and retention at 12 weeks follow up. 4. Process evaluation of all of above study processes and acceptability of THEHOPE.


Research activity codes: 4.3 INFLUENCES AND IMPACT;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: MENTAL HEALTH
Title: The DREAM Project: Diversity, Research, and Engagement for Adolescent Mental Health
Funder: Medical Research Council

Abstract: The number of children and adolescents from migrant backgrounds is increasing in the UK, with evidence that they may be at increased risk of poor mental health outcomes due to exposure to psychosocial stressors before, during, and following migration. There is limited evidence on protective or preventive interventions to promote mental health and well-being in migrant children and adolescents, and a lack of community engagement or participatory research to support effective implementation. However, creative and arts-based approaches have been used to both facilitate meaningful engagement and to promote mental health and resilience. The aim of this project is to utilise participatory research and engagement to strengthen evidence on the mental health needs of children and adolescents from migrant backgrounds, and approaches to promoting their mental health and well-being. The specific objectives across three interlinked work packages are to: 1) Establish a sustainable foundation for community engagement and participatory research through a multidisciplinary research network, and youth consortium; 2) Investigate mental health needs, and conceptualisations of risk factors, resilience, and barriers to engagement among children and adolescents with migrant backgrounds through a mixed-methods survey and photovoice project; and 3) Develop, pilot, and evaluate a co-produced arts-based mental health promotion intervention through collaboration with the youth consortium and research network.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Virtual food for real thought: how to improve extinction learning in anorexia nervosa
Funder: Medical Research Council

Abstract: Anorexia nervosa is a deadly psychiatric disorder primarily characterised by eating-related anxiety. No currently available psychological treatments include the provision of effective meal support for adults with anorexia nervosa. The aim of this study is to use virtual reality to test the mechanisms of extinction learning and help patients to develop a more positive relationship with food. The hypothesis is that exposure to virtual foods enhanced by positive mood induction or recovery-focused social support will be associated with greater reductions in food-related anxiety and greater caloric intake during a taste test, compared to exposure to virtual foods alone. This hypothesis is based on recent advances in the science of learning. These advances consist in the understanding that extinction of previously acquired negative associations can be enhanced by strategies that inhibit the reacquisition and return of fear and boost the development of safer associations (i.e. positive mood and social support). Adult patients with anorexia nervosa will be recruited (N=159) and randomised to one of three experimental conditions: (1) exposure to virtual foods, (2) exposure to virtual foods enhanced by positive mood induction and (3) exposure to virtual foods enhanced by recovery-focused social support. Anxiety and behaviours towards virtual foods will be measured during exposure to a virtual kitchen and caloric intake will be recorded during a taste-test. This project paves the way for the understanding of the mechanism of extinction learning in anorexia nervosa and other fear-related disorders. The use of virtual reality ensures high levels of experimental control to test causal relationships between variables, as well ecological validity and relevance. Clinical implications include the development of a novel intervention to shape the process of behaviour change around food and eating in anorexia nervosa.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES;3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: SCAMP Wave 2
Funder: Medical Research Council

Abstract: Mental illness commonly emerges in adolescence. Excessive use of digital technology (e.g. social media) is associated with poor mental health, but underlying mechanisms are not established. The Study of Cognition, Adolescents and Mobile Phones (SCAMP) is a prospective cohort uniquely placed to investigate the multifactorial pathways by which the contemporary digital environment may affect mental health during adolescence. The programme aims are: 1) to investigate direct and indirect mechanistic pathways and genetic risk factors to better understand how digital environments might affect mental health from adolescence to adulthood; 2) to enhance SCAMP as a major national/international resource for research into adolescent mental and physical health. We will do this via face-to-face follow-up of SCAMP participants 6 years post baseline at age 17/18 years; followed by 3-4 years of remote follow-up via an app; and ongoing linkage to routine health/educational records. We will collect repeat and new measures of mental health, cognition, technology use and potential confounders, plus biosamples and anthropometry. Objective data on digital technology use and physical activity will also be collected via the app and a fitness tracker. Participant DNA from biosamples will be genotyped. We will use these data to investigate the roles of physical inactivity, adiposity, cognitive development, puberty hormones and genetic risk factors in the pathways linking adolescents' digital technology use to mental health. Supported by co-design from stakeholders, this research may identify specific high-risk digital technology activities and/or high-risk population groups, thus informing development of evidence-based targeted risk reduction strategies and behavioural health promotion policies.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: STOP- Successful Treatment Of Paranoia: Replacing harmful paranoid thoughts with better alternatives
Funder: Medical Research Council

Abstract: Paranoia is associated with a range of mental health conditions, including psychosis. The lifetime rate of psychotic disorders is 3.5%. Psychosis is one of the most disabling mental health conditions, associated with distress and impairment in work, family and social functioning. Recent advances favour targeted interventions, focussing on specific symptoms or mechanisms.This study proposes to develop and test the efficacy of an app version (STOP) of a novel intervetion for paranoia (CBM-pa). CBM-pa is a self-administered psychological procedure that has been developed by combining basic research on biases in paranoia with established CBM techniques. CBM-pa is computerised and involves reading text inviting paranoid interpretations, but then generating responses reflecting an alternative, non-paranoid interpretation. A six session version has been developed and a feasibility study has been completed with promising results. In this proposal (year 1) we will develop CBM-pa into a more accessible and engaging 12 session 'STOP' app for mobile phones, adding 6 newly created sessions. We will then (years 2-4) deliver STOP in addition to treatment as usual and compare it with a text reading control condition, conducting app-based outcome assessments after every session. As suggested in previous feedback, we now propose a 2 arm dose-finding study using a randomised controlled design conducted across two sites. Retrospective time series analysis will establish the minimum number of sessions required to achieve clinically significant reduction of paranoid symptoms. To add value at minimal cost, and to provide data required by potential investors, we will include a 3 and 6 month follow up to assess long term efficacy of 12 sessions. This design will establish both the minimum immediately effective dose of STOP plus the long term efficacy of 12 sessions when this promising intervention is delivered in a form suitable for widespread patient/public use.


Research activity codes: 6.3 MEDICAL DEVICES;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH