NIHRDataInsights/HRCSData huggingface dataset:
Title: Alcohol dependence and associated disease: determinants, pathogenesis and treatment
Funder: Medical Research Council

Abstract: Our understanding of the biological mechanisms underpinning alcohol consumption and related disease onset/progression is poor. The combination of detailed phenotypic and genetic data available via UK Biobank provides the ideal opportunity to investigate specific factors associated with alcohol consumption. Traditional epidemiological methods will be used alongside GWAS (Linear mixed model approach), Mendelian randomisation and Phenome-wide association studies to examine the interplay between disease phenotypes, the causal effect of modifiable exposures on disease, and regions of genetic interest. Genetic engineering in C. elegans will be employed to understand how genes identified through UK Biobank data analysis influence alcohol consumption and metabolism. The ultimate aim is to identify novel drug targets or pathways that may be suitable for new drug discovery or drug repurposing. Theoretical and empirical observations suggest that a given level of alcohol does not impact each individual equally, with some not developing clinically significant alcohol-related organ disease and those that do, develop different target organ disease. This programme of work will investigate alcohol-related liver disease and alcohol-related brain injury. Alcohol-related liver disease: First, confirm phenotypes using primary and secondary electronic health records in UK Biobank. Second, explore phenotypic and genetic traits in cases and drinking/non-drinking controls with the aim to identify early biomarkers. Third, replicate in model organisms and well-defined human samples. Alcohol-related brain injury: Use UK Biobank brain MRI data to delineate the consequences of heavy alcohol consumption on brain structure and function. Linking genetic and imaging data will enable the association between robust SNPs or other genetic variants and brain phenotypes to be explored. The aim is to create computational and/or organism-based models of alcohol-related brain injury.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;ORAL AND GASTROINTESTINAL
Title: Alcohol marketing to LGBTQ+ communities: A scoping review
Funder: Institute of Alcohol Studies

Abstract: The review aims to bring together published research and grey literature focused on the marketing of alcohol to the LGBTQ+ community and its constituent parts. The scope will include marketing through social and traditional media, the commercial gay scene and corporate sponsorship. Specifically, we ask: i. How do alcohol companies target gender and sexually diverse communities? ii. What effect does targeted alcohol marketing have on the drinking practices of gender and sexually diverse communities? iii. What are the potential implications of targeted marketing to gender and sexually diverse communities for regulatory codes and policy in the UK?


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: MENTAL HEALTH;ORAL AND GASTROINTESTINAL
Title: The analysis of three-dimensional facial dysmorphology.
Funder: Wellcome Trust

Abstract: Facial shape is significant in a variety of medical contexts. One example is where children are born with a cleft lip and/or palate, requiring urgent treatment. However, surprisingly, there is a wider variety of medical conditions which have an associated characteristic facial shape. This happens because, as a fetus develops in the womb, the cells which develop into the face are closely associated with the processes which are involved in the development of other parts of the body, including t he brain. This kind of issue can be investigated by taking pictures of the face in three dimensions and characterising its shape. However, while three-dimensional imaging is readily available, methods for extracting relevant information from these images, and analyzing it properly, are much less well developed. Methods for analyzing complex data, in the form of curves and surfaces, are becoming available and the aim of the project is to explore the potential for this in the context of the face. One application to the development of schizophrenia, and another to the outcome of surgery on the jaw, will be studied. However, the more general analytical tools developed will be available for other scientists to use for wider applications.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH;ORAL AND GASTROINTESTINAL
Title: Mental health and incontinence
Funder: Medical Research Council

Abstract: The proposed research will examine bi-directional relationships between mental health problems and incontinence. We will examine these associations in childhood, adolescence and adulthood using data collected from children (up to age 19 years), mothers and partners from the Avon Longitudinal Study of Parents and Children and data on incontinence from linked health records. We will conduct complementary analyses in adults using data from UK Biobank to provide us with increased statistical power and the ability to extend our analysis to older adults. The proposed project will be the first to apply novel and robust causal inference methods to examine if the relationships between mental health and incontinence are causal, and to examine the mechanisms underlying these relationships. Wherever possible, we will compare assumptions and conclusions from different methods to strengthen causal inference and to better understand the impact of various potential sources of bias on our conclusions. We will use a latent variable framework of general structural equation models (SEM) to provide maximum flexibility, allowing complex SEMs to be developed incrementally using several smaller sub-models. We will apply a range of statistical methods to examine whether relationships between mental health problems and incontinence are causal, including propensity score-based methods, marginal structural models, negative controls, and Mendelian randomisation (MR) analysis. We will examine potential mediators of the relationships between mental health problems and incontinence in ALSPAC data using a causal mediation approach based on counterfactual theory.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: MENTAL HEALTH;RENAL AND UROGENITAL
Title: Maternity-related outcomes in women with a diagnosis of non-affective psychotic disorder: a data linkage study in two Scottish cohorts.
Funder: Chief Scientist Office (Scotland)

Abstract: Women diagnosed with non-affective psychotic disorders (including schizophrenia) are at greater risk than the general population of adverse outcomes of pregnancy including antenatal and delivery complications. Local intelligence is absent regarding birth rate per annum for this group, and the perinatal health needs of these mothers and their offspring are poorly understood. This project will take advantage of routine data in north-east and west Scotland to establish a large Safe Haven cohort of women with a lifetime diagnosis of psychotic disorder. Patient records will be linked to the Aberdeen Maternity and Neonatal Databank or ISD SMR-02 maternity data to estimate birth rates per annum and explore maternity-related outcomes. Women with psychosis (exposed individuals) who have given birth in each area will be matched on parity and deprivation with 3 unexposed individuals to explore associations between a history of psychosis and maternity-related events, taking into account demographic factors.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Investigating a placental origin for pregnancy and postpartum mood disorders:
Funder: Medical Research Council

Abstract: Four investigators will bring together their skills in placental epigenetics, behavioural and molecular neuroscience, obstetrics and perinatal psychiatry to tackle one of the greatest challenges of perinatal medicine - understanding why pregnancy provokes maternal mood disorders in some women. Mothers are exposed to very high levels of placental hormones during pregnancy. Data from animal models suggest that these hormones are important for maternal behaviour. Several imprinted genes regulate the endocrine compartment of the placenta suggesting a role for placental epigenetics in maternal behaviour. We will examine maternal behaviour in an animal model in which the endocrine compartment of the placenta is compromised by genetically altered expression of an imprinted gene. In preliminary work, we find that wild type females change their behaviour towards their pups and show altered brain gene expression in response to our placental mutation. Concurrently, we will undertake a study examining the expression of imprinted genes and hormones in term placenta from women assessed for symptoms of depression (Edinburgh Depression Scale) and anxiety (Spielberger State/Trait Index) before and immediately after delivery. We will initially apply targeted RNAseq and pyrosequencing to a set of discovery placental samples representing extreme moods to obtain further evidence that imprinted genes and placental hormones are aberrantly expressed. Our pilot data identified significantly altered placental expression of an imprinted gene and placental lactogen associated with prenatal depression. Finally, we will bring these two projects together to test the function of the most promising candidate gene identified in our human study in the experimental protocol established using our current animal model. At the end of this study we will have a list of gene changes associated with maternal mood disorders and experimental evidence that these play a causal role.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Individualising the risk of recurrence for women with bipolar disorder in the perinatal period
Funder: Medical Research Council

Abstract: Aims: The primary aim of this study is to understand better the factors that influence an individual woman's perinatal risk of a bipolar recurrence, which will enable women and their clinicians to make better informed decisions about their care. I will do this by: 1) recruiting a large, well characterised, cohort of women with bipolar disorder in pregnancy and following them up through to the postpartum; 2) developing prediction models of the risk of recurrence of bipolar disorder for women in the perinatal period (pregnancy and up to 6 weeks postpartum) in an existing large cohort of parous women with bipolar disorder; 3) validating the models and exploring additional risk factors in the prospective sample of pregnant women with bipolar disorder and an electronic records database. Plan of investigation: My project will involve recruiting and conducting data analysis of a prospective sample of pregnant women (n=300) to build on an existing pilot of 120, and data analysis of a retrospective sample of parous women from the Bipolar Disorder Research Network, BDRN (n=2,181). Participants will be assessed with a semi-structured interview and complete questionnaires on mood and personality. Medical and psychiatric case notes will be collected. Women who are pregnant will be assessed at two time points (third pregnancy trimester; 3 months postpartum). I will use multivariate statistical methods (including regression models) applied to risk prediction modelling. I will choose variables based on the literature, and clinical and patient experience that are known or may plausibly be associated with vulnerability to the puerperal trigger. I will test model performance, namely discrimination (e.g. c-index) and calibration (e.g. plots). I will test internal validity using bootstrapping techniques. The final model will be tested in external samples. The findings can then be used to develop more formal decision-aids and to inform perinatal healthcare policies.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Improving health systems responsiveness to neglected health needs of vulnerable groups in Ghana and Vietnam
Funder: Medical Research Council

Abstract: The socio-economic growth in many LMICs has improved availability of healthcare, where people increasingly demand health systems to be more responsive to their needs. Yet of all health systems goals, responsiveness is the least studied particularly in LMICs. This study seeks to contribute to improving health systems responsiveness in LMICs through the case studies from Ghana and Vietnam. We will co-produce, implement and evaluate context-sensitive interventions to improve health system responsiveness to neglected mental health needs of vulnerable pregnant women. We interpret systems responsiveness as socially-constructed interactions between the people and their health systems. We will use a mixed-methods theory-driven case study design, combining qualitative and quantitative methods. In each country, we will focus on two district health systems as our case studies. In each, we will intervene in the district hospital and 2-4 public and private primary health care facilities. However, we will also engage with relevant decision-makers at the province and national levels to ensure longer-term sustainability, replication and scaling up. This 42-months study will include three Phases. In Phase 1, we will review theories of how responsiveness works and explore actors' expectations of responsive systems. In Phase 2, we will co-produce the context-sensitive interventions to improve health systems responsiveness to health needs of vulnerable groups. In Phase 3, we will implement and evaluate the interventions within the local contexts to inform their integration within routine practices. Decision-makers will be engaged through embedding research in policy and practice. The study outcomes will be: 1)improved health systems responsiveness to health needs of vulnerable groups and 2)a model of complex relations between the contexts, mechanisms and outcomes of the interventions, along with transferable best practices for scalability and generalisability.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Improving maternal mental health in South East Asia through assets based approaches.
Funder: Medical Research Council

Abstract: Perinatal mental illness can have negative, long-term impacts on the wellbeing and welfare of women, their children and families. It is associated with poor child development and in LMIC it results in higher rates of low birth weight, reduced breast feeding, severe malnutrition and hampered growth. South East Asia is a culturally and ethnically diverse region comprising several countries categorised as lower middle income or lowest income. There are severe problems of lack of access to trained mental health staff in many areas and issues of stigma and blame associated with mental ill health. We plan to expand our pan-South East Asia Perinatal Mental Health Research Network bringing together a multi- disciplinary group of experts from diverse fields of research, clinical practice, but especially third sector and representatives of women's groups. Malaysia will be the network hub building on its recent economic and health improvement and existing collaborations in Indonesia, Thailand and Myanmar. Through exchange visits, workshop and website fora we will begin to address the research priorities already identified in an intensive 2-day workshop that involvedinvolving experts from the four (4) South East Asian countries. The research network, when fully developed, will have the capacity and expertise to undertake large-scale research for development and implementation of culturally appropriate screening tools and low cost community based interventions to improve perinatal mental health, undertaking qualitative research to determine the significance of social and environmental factors to maternal psychological distress among diverse communities.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY);5.3 MEDICAL DEVICES
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Menstrual health solutions for out-of-school adolescent girls
Funder: Medical Research Council

Abstract: This research comprises formative, multi-disciplinary, observational studies among out-of-school adolescent girls aged 10-19 years in rural western Kenya. Such girls, defined as those not having completed secondary education, including school dropouts, streetgirls, orphans, and child brides are highly vulnerable to mental, sexual and reproductive health (mSRH) harms. This project examines girls' menstrual health (MH) and related mSRH problems, followed by an evaluation of which optimal interventions are required to reduce MH/mSRH harms, and how these interventions can be delivered in community settings. A cross-sectional survey among 1000 out-of-school girls nested in KEMRI's health and demographic surveillance system (HDSS) will identify girls menstrual needs and practices and their mSRH. Participatory field studies (focus group discussions, community transect walks, and girls menstrual journals) will generate contextual data on girls challenges, identify locational risk exposures, and explore community structures in place to support delivery of interventions. These findings and data from a systematic review and meta-analysis on critical MH/mSRH interventions and community delivery systems will inform girls and stakeholders on co-creation of optimal interventions (single or combined package). We will deliver selected interventions to 300 out-of-school girls, to assess uptake, acceptability, use, and perceived impact on key mSRH outcomes through surveys and participatory studies at timepoints during intervention, and evaluate challenges associated with intervention delivery. Outcomes will presented to stakeholders to consider recommendations for large-scale implementation studies, including preparation for a formal multi-site trial. Findings, methods, and tools will be widely disseminated to inform MH/mSRH researchers and stakeholders internationally. The platform established to reach out-of-school adolescents can be used for other research programmes.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Perimenopause and risk of psychiatric disorders: a longitudinal, population-based study
Funder: Medical Research Council

Abstract: This study will be the first longitudinal, population-based, systematic investigation of the risk of psychiatric disorders associated with reproductive aging. It seeks to contribute addressing the gender gap in psychiatry highlighted by professional bodies and institutions worldwide. First, we will seek to estimate the risk of psychiatric illness associated with reproductive aging and to test the hypothesis that, compared to the reproductive and late post-menopause stages, late perimenopause is a period of increased risk of psychiatric illness. The primary analysis will include all women in UK Biobank who had their final menstrual period before 2010 (N=165,406). Linkage with pre-existing primary care and hospital electronical health records will provide longitudinal clinical information. The main outcome will be incident ICD-10 psychiatric diagnoses. Relative risks will be estimated using the period up to 10 years before the final menstrual period as a reference in survival analyses. Group-based trajectory modelling will identify groups of women with similar disease trajectories. Second, we will evaluate the effect of possible predictors [reproductive (psychiatric) history, hormone replacement therapy, psycho-social factors, aggregated measures of genetic variation] on the risk of late perimenopause psychiatric episodes and on the group membership of disease trajectories. Replication efforts will exploit our in-house large clinical-genetic datasets. To maximize the impact of our research, an advisory board of women with lived experience will be involved at all stages of research and will lead dissemination activities. Through our links with professional organizations, the results will have the potential to directly inform clinical practice. By providing evidence-based, easy-to-understand information to the public, this research may also contribute to the empowerment of women and to de-stigmatizing and raising awareness of perimenopause mental health.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: The microbiota-gut-brain axis in preterm infants
Funder: Wellcome Trust

Abstract: Around 11% of infants are born preterm (<37 weeks of gestation). Preterm birth associates with atypical brain development apparent on magnetic resonance imaging (MRI), and with increased risk of developing special educational needs later in life. Preterm infants also have different composition of gut microbes. The gut microbiota plays an important role in stress response, anxiety and social behaviours, and alterations in its composition are associated with cognition and temperament in childhood, and depression in adults. We aim to investigate the relationship between gut microbiota and early brain development in preterm and healthy term-born infants. First, we will characterise gut microbial composition in infant stool samples and investigate which perinatal factors (e.g. mode of delivery, exposure to breast milk) influence gut microbiota. Second, we will use brain MRI to evaluate how variations in gut microbial composition relate to the integrity of developing brain connections. Third, we will investigate the associations between gut microbial composition and neurobehavioural outcomes (e.g. attention, social cognition, anxiety) in these children at 2 years. These studies will determine whether the gut microbiota modifies risk or resilience for healthy brain development in preterm children. If it does, it may inform novel therapeutic strategies to improve neurocognitive outcomes.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Untreated depression or antidepressant use during pregnancy: what are the outcomes?
Funder: Wellcome Trust

Abstract: Depression is a common mental health problem and the use of drugs, known as antidepressants, are being prescribed more and more to help people with depression. Pregnant women also suffer from depression and may need antidepressants, however we don't know enough about their potential harms to give good advice to women about whether these drugs are safe in pregnancy. In this PhD, I will use GP data to try and understand the effects of antidepressant use and untreated depression during pregnancy on the baby. I will look at three groups of outcomes: pregnancy (including miscarriage and stillbirth), birth (including whether the baby is born early or is small when it is born) and childhood (including autism) outcomes. I will use a range of methods that use statistics to tackle the different sources of bias that pose a problem to this kind of research; in doing so, the overall conclusion of whether antidepressant use during pregnancy negatively impacts on these outcomes or not will be more accurate than previous studies that only use one or two methods. In order to properly communicate risk, I will work with patient groups to ensure that the findings best explain the findings without placing blame.


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