NIHRDataInsights/HRCSData huggingface dataset:
Title: Establishing a child and adolescent twin register for research and capacity building on the aetiology of mental illness in Sri Lanka and other LMIC
Funder: Medical Research Council

Abstract: The aim is to establish a register of child and adolescent twins with consent to be approached for future research in Sri Lanka (SL). Our long term vision is to increase the impactful research volume in SL and South Asia by establishing a virtual centre of excellence on cohort studies. The initial focus will be to plan research on aetiology of mental illness, the impact of challenges to early brain development on mental health, and to enhance understanding of genetic, developmental, environmental, social and cultural contributions to aetiology. Twin studies offer a strong methodology for studying complex phenotypes and their underlying biology. Three pillars underpin the initiative: high quality research, ethics, patient and public involvement and engagement (PPIE, a novel concept for South Asia). We have assembled world leading researchers in research methods, ethics, PPIE, and grant development. Capacity building of junior academics across the partnership will develop future research leaders and core skills on child/adolescent mental health and twin methods. We will identify key research questions and develop proposals for funding considering existing gaps in knowledge. Outputs are a sampling frame of younger twins, some with linkage to parental data via an existing adult twin register, and a core set of data feasible to be collected from routine records on children's health and education. Other data (questionnaires, biometrics) will be identified through individual future projects. The main partner, the Institute for Research and Development (SL), has established a large, functioning, population-based adult twin register. The IRD successfully carried out two waves of studies, recruited a matched non-twin cohort and established a biobank and a genetic laboratory. Other partners are Kings College London, University of Bristol, Independent University of Bangladesh, Health Services Academy-Islamabad, Pakistan, and All India Institute of Medical Sciences.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: MENTAL HEALTH
Title: MICA BRAINTOOLS Phase 1: Optimising neurodevelopmental outcomes for global health
Funder: Medical Research Council

Abstract: Our cohesive package of work involves four related pump-priming projects (PPP). PPP-A: We will develop and field-test a toolkit for measuring early childhood brain markers associated with mental health outcomes, using combined EEG and eyetracking to enable a fully automated analysis pipeline suitable for large-scale deployment. The task battery will assess social brain development (e.g. videos of social dynamic scenes; face attention; dynamic gaze) and attentional control (e.g. gap-overlap attention-shifting; frontal EEG power and connectivity); tools are designed to be applicable to other domains as novel findings emerge. After development, we will assess test-retest reliability and feasibility in two contrasting rural LMIC settings. PPP-B: To boost human capital, we will develop a new Masters program in "Developmental Neuroscience for Global Health" and submit it for accreditation. This will foster expertise, collaboration, and training between the UK and LMICs. PPP-C: Our tools are targeted at early childhood, and critically require engagement with families. To facilitate this, we will collaborate with a Birkbeck spin-off company, BabyBrains Ltd, that provides empowering parental education (www.babybrains.com). The CEO of BabyBrains will visit the LMIC sites to consult on how their program can be best adapted, and produce draft training materials for future work. PPP-D: LMIC-based research requires local Centres of Excellence (CoE) that have the infrastructure, expertise and tools required to conduct large-scale studies of early development. A roadmap for creating two CoEs will be developed; West Africa (MRC-G) and India (Sangath). These CoEs will provide training for both local and UK-based researchers in applied global health research; and through a hub and spoke model enable our scientific advances at CBCD to be rapidly rolled out to the broader global community.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH
Title: Community violence and adolescent mental health in Brazil
Funder: Medical Research Council

Abstract: Community violence is consistently associated with mental health problems in high-income countries, in particular depression and post-traumatic stress disorder (PTSD). Brazil reports strikingly high levels of community violence - such as homicide, gang and drug-related violence - and adolescents are particularly vulnerable, with 59% of deaths among Brazilian adolescents being due to homicide in 2009. Very little research exists on the association between community violence and adolescent mental health in Brazil nor on the effect of policies or interventions to manage, reduce and prevent the resulting mental illness burden. The current projects provide preliminary data for future sustainable, large-scale, global mental health research on community violence and mental health and to establish a strong collaboration between Brazilian and UK researchers by building on existing ties and developing new ones through four activities: 1. Secondary analysis of existing longitudinal prospective cohort data from Pelotas and Salvador, on the association, directionality and temporal relationship between different types of community violence and depression, PTSD and conduct problems. 2. Data linkage of national datasets to assess the effect on mental health of violence-reduction policies in future work. 3. Pilot data collection to assess the validity of a new measure for ICD-11 PTSD and complex PTSD diagnoses and qualitative work to refine a community violence measure. 4. A workshop to identify evidence-based policies and research priorities in order to reduce, manage and prevent the mental health burden resulting from community violence among adolescents. Attention will be paid to future research on underlying cognitive and neurological mechanisms and expanding findings to other violent Latin American LMICs. Understanding how and to what extent community violence impacts mental health and what can be done to tackle this problem represents a public health priority.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: A Network for Studying Psychological Resilience in Low and Middle-Income Countries (NESP)
Funder: Medical Research Council

Abstract: Vulnerability or resilience to common mental health disorders is related to the combination and interaction of genetic susceptibility, early life factors and an individual's current environment. Over 95% of studies addressing these factors have been confined to High income countries (HICs) however, very little is known of these factors in low and middle-income countries (LMIC), where the burden of such common mental health disorders is even more substantial. Here we propose to develop a network of global leaders to analyse the key factors in three contrasting LMIC settings. This will enable us systematically to determine the processes leading to vulnerability or resilience to common disorders of mental health and exploit this knowledge, enabled by leading data sciences and in-country expertise, to develop specific approaches to reinforce resilience and support prevention, diagnosis and treatment. Our approach is highly multidisciplinary, combining genetic, clinical and social sciences expertise to provide a comprehensive view of an individual's genetics, development and environment. We will combine this expertise with world-leading informatics capacity to create a network for the study of psychological resilience across diverse environments and economies. The long term aims of this pump-priming grant are to conduct high quality multidisciplinary research into the epidemiology and aetiology of resilience and mental disorders with our partners - extending awareness of risk factors, knowledge of illness and preventative protective systems. We also seek to build a linked community in each country with local leadership to lead a mental health research programme over the coming decades and establish connections between these three different regions (each with their different economic, social, and cultural systems). This will help position our partner countries as centres of mental health research within regional and wider international networks.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: MENTAL HEALTH
Title: Identifying Depression Early in Adolescence (IDEA) King's-Brazil-Nepal-Nigeria network
Funder: Medical Research Council

Abstract: Depression is a leading contributor to the global burden of disease and, for most individuals, depression has its onset in adolescence and young adulthood. Youth in low- and middle-income countries (LMICs), who comprise 90% of the world's child and adolescent populations, bear the greatest burden of depression. Moreover, one out of every three suicides each year are among adolescents and young adults in LMICs, accounting for ~300,000 deaths each year. To combat this global public health challenge, more research is needed to identify risk and resiliency factors to detect and prevent depression during adolescence, especially within the LMIC context. The key aims of King's College London's proposal are: to consolidate a recently formed multidisciplinary UK-Brazil-Nepal-Nigeria network of early and mid-career researchers, and build capacity within LMICs to pave the way to apply for more substantive grants to increase understanding of biopsychosocial risk and resiliency factors for depression in adolescence. This would greatly improve early detection of depression across the globe, and ultimately lead to the development of context-specific treatments and preventive interventions. This will be achieved through: (1) Two in-person networking meetings of early- and mid-career researchers and clinicians from King's, universities in Brazil and Nigeria, and an NGO in Nepal, will be held to discuss harmonisation of measures across existing cohorts, reach consensus on a uniform set of assessments for future large-scale research in these settings, and develop a substantive grant application. (2) Undertaking pilot analyses of replicability of a Brazilian depression risk score in adolescents from cohorts in the UK, Nepal and Nigeria. (3) Conducting scoping exercises to ascertain the viability of conducting large-scale neurobiological psychiatric research in the 3 LMICs. (4) Building capacity by providing virtual training and apprenticeships to researchers in each LMIC.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: MENTAL HEALTH
Title: The influence of Executive Function on Mental Health in vulnerable adolescents: a multi-site low and middle income country approach
Funder: Medical Research Council

Abstract: Executive function (EF) is complex set of skills which have three core functions: inhibition and interference control, working memory and cognitive flexibility. These functions are used for reasoning, problem solving, and planning everyday activities. EF is critical for children's development, influencing cognitive, academic and social functioning. Impairment is associated with mental illness such as anxiety, attention deficit hyperactivity disorder and depression. It has two periods of rapid development i.e. early childhood and adolescence. Biomedical factors, such as a poor nutritional status and HIV, adversely affect both the neural substrates of EF and performance on EF tasks. In addition, chronic poverty affects EF through exposure to multiple psychosocial stressors. These factors are common in Low and Middle Income Countries (LMIC) and are likely to be major determinants of adolescents achieving their potential, being able to contribute to society through employment and social functioning, and achieving mental health. The role of EF in risky behaviour and mental health is a strong focus of investigators across multiple Departments at the University of Oxford. Research in this area is already being carried out in collaboration with investigators in LMIC by Abubakar and Newton in Kenya; Kahn and Scerif, Demeyere and Stein in South Africa; Favara and Sanchez in Ethiopia and Peru. The pump priming grant allows these different groups to develop a common assessment platform and develop strategies to improve EF to enhance mental health and decrease risk behaviours. A key component of the work will be the harmonisation of instruments to measure EF in LMIC. Numerous studies have shown that EF can be improved; either through direct cognitive stimulation or indirectly through enhancing the psychosocial environment, and we plan to identify contextually appropriate interventions to improve EF in adolescence.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH
Title: Confidence in Global Mental Health Research
Funder: Medical Research Council

Abstract: Early adversity is strongly associated with subsequent mental health, but for many adversities it remains unclear whether these associations are causal, which hampers the development of effective intervention. At the same time, the exact nature of the adversities experienced by young people varies considerably across countries and regions, and most research conducted to date has relied on data from high income countries. We propose a programme of seed funding and capacity building focused on partners in LMICs that will allow early- and mid-career researchers from the University of Bristol and our partner countries to develop research proposal to explore these questions in detail, focusing on issues of particular relevance to these partner countries and their wider regions. Bristol's internationally-recognised excellence in epidemiology and in particular causal inference (e.g., Mendelian randomization) will support these efforts, providing core training in relevant skills as well as bringing expertise in the establishment and implementation of large-scale cohort studies.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Neurodevelopmental disorders in LMIC settings
Funder: Medical Research Council

Abstract: We estimate that many children in low and middle income (LMIC) settings have neurodevelopmental disorders (NDD) due to a multitude of causes (e.g.infections, nutritional deficiencies, trauma in antenatal, perinatal and postnatal period. At present we have no definitive data due to the lack of tools which can screen and identify children. Most tools used in high income settings are culturally specific, proprietry and require training. With few specialists in LMIC settings we have been unable to do research to provide the evidence. In this study we will create the first network of professionals and researchers who are specifically interested in identifying and creating better feasible, diagnostically acurate, sensitive and specific tools for early identification of NDD. An ongoing funded study (CHAIN NDD - Children with Acute Illness Network Neurodevelopmental Substudy) in Uganda, Malawi and Pakistan provides a network of sites, interest and expertise. Aim 1 will be to hold two network meetings (UK and Uganda). Meeting 1 will aim to identify already existing tools, cohorts and databases with information on children who have been definitively diagnosed with NDD. The group will make a data analysis plan. Meeting 2 will feedback results and provide an opportunity to co-write a collaborative grant to demonstrate diagnostic utility of a tool to identify children with NDD at 0-3 years. Aim 2 will be to conduct a diagnostic utility study using GAMLSS statistics to look at performance of Malawi Developmental Assessment Tool (MDAT) Z-scores collected in 600 CHAIN NDD in children with a definitive diagnosis and those with no diagnosis (as provided by an expert neurodevelopmental paediatrician). This grant will enable definitive diagnosis to be made on at 50 additional children to provide this data. Aim 3 will enable a stakeholders meeting in each site to gain information on feasibility and pathways presently available for identifying and referring children.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH
Title: GCRF: Trauma and Adverse Childhood Experiences Springboard (TrACES)
Funder: Medical Research Council

Abstract: TRACES is a collaborative programme of research between the University of Exeter (UoE) and partners in South Africa, Uganda, India, Jamaica, Guyana and Colombia focused on early life trauma (including adverse childhood experiences) and its trajectories to mental illness, substance abuse and violence-related outcomes. Early life trauma (ELT) is highly prevalent, especially within low- and middle-income countries (LMICs) and is strongly associated with a wide spectrum of mental illness (including psychosis, mood and anxiety disorders, addictions, suicide and personality disorders). The major part of the global burden of these disorders is located in LMICs, yet research on the mechanisms and pathways through which ELT interacts with other aetiologies and leads to later mental illness is limited outside of high-income contexts. Research to date suggests that early trauma acts through epigenetic processes, disregulates hypothalamo-pituitaryadrenal pathways and immunological processes and disrupts cognitive-affective development. There is an urgent need to investigate these and other mechanisms within diverse geographical, social and cultural contexts so as to move forward our understanding and provide a basis for developing and testing interventions aimed at mitigating the effects of ELT and preventing consequent mental, substance and violence-related outcomes. Adopting a developmental life-course perspective and a translational approach including multidisciplinary methods (i.e. genomics and epigenomics, neuroimaging, psychopharmacology, clinical, social and spatial epidemiology, cognitive and experimental neuroscience and neuropsychology), this programme provides pump-priming funding to support collaborative workshops, network-building and pilot studies that will establish our international research platform and provide a springboard for large-scale, multidisciplinary and collaborative grant applications that will enable this ambitious programme of research.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: MENTAL HEALTH
Title: Psychiatric Imaging
Funder: Medical Research Council

Abstract: Psychotic disorders such as schizophrenia are amongst the top ten causes of disability in adults- accounting for one in every ten hospital beds used in the UK. The main treatments, the antipsychotic drugs, were discovered over fifty years ago. Since then there has been limited progress as: i) the medications are still based on the same old principle (dopamine (DA) receptor blockade), ii) there are no good predictors of response so treatment proceeds by trial-and-error, and iii) current treatments are ineffective for one in three patients. A major limit for the development of new, rational treatments has been the lack of a defined etiology and limited knowledge of the pathophysiology of schizophrenia. As a result most drug development in the last fifty years has simply sought to emulate aspects of existing antipsychotics and/or has used empirical animal models (e.g.: conditioned avoidance response or PCP-induced locomotion) that were developed prior to clear knowledge of the pathophysiology.|However, there is now evidence of a defined neurochemical pathophysiology in psychosis. Over fifteen in vivo studies in the last decade point to one central fact: presynaptic DA dysfunction is the final common pathway leading to psychosis (data reviewed and synthesized in: Howes et al, B J Psuch, 2007 & Lyon et al. Schiz. Bull. doi:10.1093, 2009). For this reason understanding the causes and implications of presynaptic DA dysfunction is critical to the pathophysiology of psychosis and provides a framework for understanding risk factors, predicting onset and delivering new treatments as set out in a recent review of the area (Howes and Kapur, Schiz Bulletin, 2009). The programme is divided into four sections: (a) Risk factors to pathophysiology; (b) Predicting illness onset; (c) Pathophysiology to therapeutics; (d) Targets beyond dopamine.|The first section will investigate the effects of the two major environmental risk factors for psychosis - cannabis use and social stress/defeat - on DA function using F-DOPA and raclopride positron emission tomography (PET) in individuals exposed to these risk factors. Section 2 addresses the ultimate aim in therapeutics of psychosis - predicting and preventing its onset using PET and magnetic resonance imaging (MRI) to identify biomarkers and pathoetiological changes underlying the development of psychosis. One third of patients with established psychosis fail to respond to treatment. Section 3 will investigate the determinants and predictors of treatment response using PET and MR spectroscopy of dopamine and glutamate markers respectively. Section 4 investigates upstream modulators of DA to identify novel non-D2 targets for drug discovery using agents that act at DA autoreceptors and glutamatergic and other regulatory mechanisms.|These studies have the potential to identify prognostic markers for psychosis and new therapeutic avenues to treat established illness.|


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH