NIHRDataInsights/HRCSData huggingface dataset:
Title: Developmental Trajectories in Autism Spectrum Disorder from 6 months to 7 years
Funder: Medical Research Council

Abstract: There is significant variability in the presentation of both the core defining symptoms and the presence and emergence of co-occurring psychiatric symptoms in individuals with ASD across development. However, the influences that underlie this variability are not well understood. We propose to follow-up to mid-childhood a cohort of infants at high familial risk of ASD by virtue of older sibling diagnosed. The cohorts have previously been assessed using a range of experimental techniques (EEG/ERP, eye-tracking, observations, behavioural experiments) to measure neurocognitive function (e.g. social attention, executive attention) at ages 6-10 months, 12-15 months, 2 years and 3 years. At each time point we have also acquired direct observational and parent-report measures of developmental and language ability, adaptive behaviour and age-appropriate measures of the ASD phenotype and emergent temperamental/psychiatric phenotypes (e.g. activity/ADHD, behavioural inhibition/anxiety). We propose to conduct an age-progressed parallel battery of neurocognitive experiments and behavioural assessments at 7 years. We will adopt structural equation and growth curve modelling approaches exploiting the multiple time-points at which both neurocognitive and behavioural measures have been taken in this intensive repetitive sampling design (5 time-points across 7 years). Our large and deeply phenotyped cohort provides a unique opportunity to identify infant neurocognitive stratification markers of childhood trajectories of core and associated symptoms of ASD. By these means we will be able to test hypotheses about the underlying developmental mechanisms that could stratify phenotypic heterogeneity in ASD. This, in turn, will identify both the potential timing and the targets of mechanistic-based pre-emptive interventions for the core defining features of ASD and for the common co-occurring psychiatric conditions that emerge in early childhood.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH
Title: IMPC: Disruption of PDZD8 as a potential cause of intellectual disability
Funder: Medical Research Council

Abstract: Intellectual disability (ID) is a common neurodevelopmental disorder with an onset of cognitive impairment before the age of 18 years and is characterized by significant limitations in intellectual functioning and adaptive behaviour. ID can have a devastating effect on the lives of the affected individuals and their families and is a major challenge at the clinical level. The condition affects 1-3% of the world population; however, its prevalence in the developing world is almost twice that of the affluent world. Among the known causes, ~50% of ID cases have a genetic aetiology, such as chromosomal abnormalities or mutations in specific genes. Consanguineous marriages are practiced by about 20% of the human population and lead to a marked increase in the frequency of severe recessive disorders. Homozygosity mapping has been proven to be an effective method for gene identification in consanguineous populations. To this end, we recruited six families derived from first-cousin marriages in which at least two children were affected by ID. In one family, genetic testing revealed a truncation mutation in PDZD8 that co-segregates in the homozygous state with ID. Our overarching aim now is to elucidate the role of PDZD8 in cognition, and how homozygous disruption of PDZD8 leads to ID. We recently discovered that knockdown of the PDZD8 orthologue in Drosophila (CG10362) led to a deficit in long-term memory. The availability of Pdzd8 null mice provides direct access to the biological effects of PDZD8 deficiency in mammals. Therefore, we propose to use the Pdzd8tm1b mouse model to increase understanding of the effects of disruption of PDZD8 expression on phenotypes relevant to cognition and ID. If we find that Pdzd8 null mice exhibit a phenotypic resemblance to ID, we will prepare a subsequent proposal to employ these mice as a model system for testing hypotheses about the mechanisms underlying the condition, and translational evaluation of treatments for the condition.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: MICA: Improving the mental health and well-being of foster carers by reducing compassion fatigue: an assessment of feasibility.
Funder: Medical Research Council

Abstract: Providing foster care for vulnerable children, who have often experienced abuse/neglect, trauma and loss (1,2,3), is demanding and stressful work (4,5,6). It requires foster carers to be have robust mental health and well-being due to the complex demands placed on them by the children in their care. Foster carers are at risk of experiencing compassion fatigue (emotional and physical burnout and/ or secondary traumatic stress) due to the demands of their role (4). The foster carer's home is also their place of work, so there is little opportunity to have a break to rest and re-charge.This not only affects their mental health and well-being, but also impacts upon the quality and consistency of care provided to the vulnerable children they look after (4). A multi-stage intervention to reduce symptoms of burnout and secondary trauma and increase feelings of compassion satisfaction in foster carers has been proposed in collaboration the National Association of Therapeutic Parenting (NATP). This will combine three of the NATP's current discrete interventions - 1)education about the signs, symptoms and management of compassion fatigue, 2) peer support and 3) access to online support materials, into one cohesive multi-stage intervention. The proposed study has been designed to: a) develop a sound logic model, b) assess the feasibility of trialling the intervention to foster carers experiencing symptoms of compassion fatigue, in order to improve their mental health and well-being and enable them to provide a more stable, empathic and consistent care environment for the vulnerable children they look after. and c) develop a manual and online support materials. The assessment of feasibility will focus on six key areas: practicality, adaptability, demand/ use, acceptability, implementation and integration. An advisory group comprising foster carers, practitioners and policy makers will guide the study.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;7.1 INDIVIDUAL CARE NEEDS
Health categories: MENTAL HEALTH
Title: Preventing Hospital Re-admissions for People with Severe Mental Illness in East Africa (PRISM)
Funder: Medical Research Council

Abstract: The global burden of severe mental illness (SMI) is well established, as is the human rights implications for the health and wellbeing of patients, caring responsibilities and burdens, and the economic situations of families and communities (Patel et al, 2016, p. 1672). These implications are especially acute in low income countries where there is less patient access to treatment, hospital care, and to a range of recovery and preventative mental health care (Hanlon, 2016). Against this backdrop, there is an ongoing need for evidence about which interventions work best (Hanlon, 2016). Preventing Hospital Re-admissions for People with Severe Mental Illness in East Africa (PRISM) is a development project that has been designed in partnership with the Ugandan NGO YouBelongHOME (YBH). YBH have begun an innovative programme working to improve appropriate, hospital to home mental health interventions with human rights values at the core. Utilising a culturally-centred, family-focussed recovery programme, YBH is based on post hospital discharge interventions to empower the family as an active agent in the returned person's recovery, and also, to connect to family, friends and communities. Despite its potential, YBH lacks systematically gathered evidence for its effectiveness in African LICs. Before conducting a trial which aims to establish this evidence, more information is needed to determine the feasibility, acceptability, and appropriateness of the YBH intervention in settings like Uganda. PRISM will undertake research in Uganda to develop a risk score to help identify patients with SMI at highest risk of readmission within three months; using action research and patient and family interviews, test and refine the YBH pre- and post-discharge intervention in Kampala; and undertake a feasibility assessment of community-based initiatives. The research findings will shape the design of a future clinical trial in East Africa.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: MENTAL HEALTH
Title: Group interpersonal psychotherapy for depression and anxiety among adolescents in rural Nepal: a feasibility and pilot study
Funder: Medical Research Council

Abstract: Depression and anxiety are leading causes of disability adjusted life years among adolescents aged 10-19 and can lead to social and educational impairment, substance misuse and suicide. The treatment gap for adolescent mental disorders is large, especially in LMICs. The WHO Mental Health Gap Action Programme outlines a role for psychological therapies in the treatment of child and adolescent emotional disorders such as depression and anxiety, however there is an urgent need to adapt these for use in LMICs. We aim to adapt and pilot the WHO group interpersonal psychotherapy (IPT) intervention for adolescents with symptoms of depression and anxiety. We will do this in rural Nepal where adolescents are at high risk of mental disorders and have limited access to mental health services. IPT was selected as the intervention because of evidence that it is more acceptable to adolescents compared to other psychological therapies, also because it can be delivered in groups by non-specialists and is therefore potentially scalable in low-resource settings like Nepal. Our study has five stages: (i) a preliminary qualitative study to understand adolescents' experiences of depression and anxiety, help-seeking and barriers to intervention; (ii) translation and expert-led revision of the IPT intervention manual; (iii) practice training; (iv) an intervention adaptation workshop and community advisory board to provide feedback on the revised manual, (v) and pilot community and school IPT groups for boys and girls to assess intervention acceptability, adherence, quality and costs, and optimal treatment duration. Our study will generate essential information on adolescent mental health intervention in LMICs and will enable us to develop a protocol for a randomised controlled trial to evaluate the effectiveness and cost value of an IPT intervention in Nepal. This study will also build research capacity and strong local and international stakeholder partnerships.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: MICA: The Translational, Computational and Neurocognitive Basis of Anxiety
Funder: Medical Research Council

Abstract: The goal of this research is to increase our understanding of the neurobiology of pathological anxiety. It has three broad aims. The first aim seeks to determine neurobiological circuitry of response to psychological treatment for anxiety. Individuals will be recruited from NHS psychological treatment services and functional magnetic resonance imaging will be used to examine cortical-subcortical brain connectivity before and after treatment. I predict treatment-related attenuation of a specific cortical-amygdala connectivity pattern relative to an anxious untreated control group. The second aim focuses on developing a novel computerised treatment for anxiety. Computational psychiatry techniques, which I have previously used to model cognitive task performance in anxious individuals, will inform the development of a new computerised treatment regimen (cognitive bias modification). I will develop a user friendly computational psychiatry toolbox, and the efficacy of my new computationally-informed treatment will be assessed in a randomised controlled trial. The final aim focuses on improving diagnosis. A translational task (and associated computational model) linked to pathological anxiety in both humans and rodents will be integrated into a large-scale human cohort with industrial collaborator Cambridge Cognition. Using data from this cohort, structural equation modelling will be used to identify latent trans-diagnostic dimensions that drive anxiety-relevant symptoms and computational-psychiatry-modelled, task performance. In the long-term these new trans-diagnostic dimensions should predict treatment response more effectively. My senior fellowship therefore proposes an ambitious research programme that combines my unique inter-disciplinary clinical, computational and neuroscience skill-set, with my breakthroughs in delineating the neural and computational basis of anxiety, to develop new and more effective clinical tools for anxiety diagnosis and treatment.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Cultural adaptation and randomised evaluation of a multi-component school- based intervention for common mental disorders in Pakistani adolescents
Funder: Medical Research Council

Abstract: Depression and anxiety are the leading contributors to health burden among adolescents worldwide. These disorders are associated with increased mortality due to suicide and intentional and unintentional injuries. If untreated, these conditions severely influence children's development, their educational attainments, and their potential to live fulfilling and productive lives. However, globally the treatment gap for mental disorders in adolescence is large. To address this treatment gap, the WHO has developed a brief transdiagnostic, group psychological intervention programme based on empirically supported cognitive behavioural therapy (CBT) techniques. The programme is called Early Adolescence Skills for Emotions (EASE). Our project has two objectives: 1) Using the MRC Framework for development and evaluation of complex interventions, we seek to understand how the WHO's EASE intervention can be made relevant, feasible and acceptable for school-going adolescents living in low socioeconomic rural settings in Pakistan. 2) Evaluate the effectiveness and cost-effectiveness of EASE using a cluster randomised controlled design. The intervention will be delivered to over 250 adolescents with symptoms of depression and anxiety in 10 schools randomised to the intervention arm, while a similar number of adolescents in 10 control schools will receive routine care and equivalent support groups. A number of questionnaires will measure outcomes at 1-week and 3-month post-intervention. Our primary outcome is psychological distress, and secondary outcomes include depression, anxiety, functioning, self-esteem and coping skills. The research will inform the WHO's efforts to lower the global mental health treatment gap for common mental disorder in low and middle income countries and help the Pakistani school system implement and establish its school mental health programme.


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: Enhancing the capacity of the Brazilian health system to support the mental health of young people
Funder: Medical Research Council

Abstract: Our research plan proposes to address health system challenges using three main activities. The first will involve generating new evidence through analysis of existing youth mental health service use data collected from all regions of Brazil to estimate the economic impact of youth mental health problems. We will use existing datasets to project regional mental health needs, services and treatments required to meet those needs and associated costs and impacts in the short and long-term. The second part will involve performing a systematic review of existing evidence for effective/cost-effective interventions for prevention and treatment of youth mental health problems. We will identify interventions which have evidence for effectiveness in Brazil or similar countries. The third part will involve synthesising the newly developed evidence from parts one and two into a practical toolkit for health and education professionals and policymakers and planners. The return on investment tool in the toolkit will expand on modelling evidence from work packages 1 and 2 on cost effectiveness. The toolkit will be built using Excel for ease of access and it will compare the costs of delivering interventions with the net potential future health and other resource costs that could be averted as a result of effective treatment or prevention of mental health problems among young people. It could also consider the value of additional positive benefits to society, e.g. increased employment participation. Following consultation with stakeholders, it will also be possible to vary estimates of selected parameters in the tool, for instance on the effectiveness, unit costs, level of uptake /use and future benefits of various interventions. We have previously used this modelling approach to estimate the case for investment and aid local and national policy making for mental health in a UK context. https://www.gov.uk/government/publications/mental-health-services-cost-effective-commissioning


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: MENTAL HEALTH
Title: Indigo (International study of discrimination and stigma outcomes)
Funder: Medical Research Council

Abstract: Aim The overall aims of the Indigo Partnership are to establish a strong research collaboration to provide the infrastructure for harmonised metrics and to develop stigma reduction interventions, and to carry out platform activities to strengthen the scientific understanding of mechanisms of action of stigma processes against people with mental illness. The longer term aim is to reduce the mental health treatment gap. Partners Participating centres are: China (Peking University Health Science Centre, and Guangzhou Medical University); Ethiopia (Addis Ababa University); Germany (University of Ulm); India (George Institute, New Delhi and NIMHANS, Bengaluru), Switzerland (WHO, Geneva); Tunisia (Hôpital Razi, Tunis); UK (KCL); and USA (George Washington University). Methods 1. Improve theoretical understanding of stigma processes by conducting the following types of platform activities to support better understanding of the underlying mechanisms of action of stigma related to: (i) unconscious bias; (ii) optimising inter-personal contact; (iii) cultural adaptation of interventions; and (iv) psychometric assessment of 7 stigma related measures in Amharic, Arabic, Hindi, Kannada, Mandarin and Telugu. 2. Incorporating these results into 3 proof-of-principle activities in the 6 LMIC sites to assess feasibility, relevance, acceptability and costs of the intervention related to primary care staff, mental health staff, and local area awareness-raising to reduce stigma. Outputs 1. A sustainable platform of collaboration across 8 countries, with established centres of research excellence. 2. Career progression for the early- and intermediate-career researchers in the low and middle income sites. 3. Publication of the results of the studies in strong peer-reviewed journals. 4. Openly available: (i) evaluation toolkit of the 7 scales for future international research use, and (ii) intervention guides for the 3 stigma-reduction interventions. 5. Pilot data that wil


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: MENTAL HEALTH
Title: E-MhGAP Intervention guide in Low and middle income countries: proof-of-concept for Impact and Acceptability (Emilia project)
Funder: Medical Research Council

Abstract: 3. Research plan, methodology and data 3.1 Research methodology and timelines 3.1.1 Overview. The Emilia project is a proof-of-concept study of the feasibility of implementing the e-version of the mhGAP Intervention Guide, and will address the 6 research questions given at 1.3. 3.1.2 Study sites. The study will take place in 2 sites: in Nepal (low income) and Nigeria (lower-middle income country), with each site including a range of urban and rural settings (see 3.5). 3.1.3 Intervention condition. The e-version of the mhGAP IG v2.0 is now being developed by the WHO and will be launched in October 2017, in both iOS and Android versions suitable for smart phones and tablets. The e-version intervention includes the following components: (i) separate translation and country adaptation in Nepal and Nigeria10; (ii) further development of the e-version of the mhGAP IG v2.0; (iii) development of a supplementary e-mhGAP IG module for Remote Supervision and Support which will be designed to allow two-way data sharing between the PHC mhGAP IG user and his/her supervisor, and for this data to be accessible offline; (iv) delivery of initial training to PHC staff for the detection and treatment of people with types of mental disorder included in the mhGAP IG; (v) delivery of ongoing supervision/support with e-mhGAP platform, and (vi) system support to address, for example, system errors that users uncover (bugs), user error, and devices malfunctioning/becoming unserviceable.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: MENTAL HEALTH
Title: Complex Trauma in Young People: Psychopathology and Cognition
Funder: Medical Research Council

Abstract: Background: Traumas are stressful events that involve danger of death, injury, or sexual violation. Complex traumas are types of trauma that involve multiple interpersonal stressors, e.g. maltreatment or bullying. Current psychiatric assessment and treatment of young people exposed to complex trauma is insufficient. To inform and improve assessment and treatment, we need an evidence-based model to describe clinical presentations in these young people. Aim: To describe psychopathological and cognitive profiles of young people exposed to complex trauma, and to investigate the origins of these presentations. Methods: Participants are from two population-based cohorts: the E-Risk Study (2,232 British young people tracked from birth-18 years); and the IMAGEN Study (2,227 European young people followed between 14-18 years). I will characterise psychopathology (wide range of disorders and symptom dimensions) and cognition (IQ, executive functions, processing speed, memory, threat perception, reward processing, risk taking) in 18-year-old participants exposed to complex trauma, compared to (i) those exposed to single-event trauma, and (ii) non-traumatised individuals. I will use regression to test for bivariate associations between complex trauma and psychopathology/cognition, and structural equation modelling to account for correlations between aspects of psychopathology/cognition and to capture higher-order group differences. I will then expand these models to include pre-trauma psychopathology/cognition and socioeconomic status (measured at age 5 in E-Risk and age 14 in IMAGEN), to test whether associations are accounted for by pre-existing vulnerabilities. Impact: Identifying previously unrecognised aspects of clinical presentations will provide meaningful guidance for clinicians. Addressing these targets could increase effectiveness of assessment and treatment, improve outcomes for affected individuals, and reduce the health service burden of complex trauma.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH