NIHRDataInsights/HRCSData huggingface dataset:
Title: Sleep-Impulsivity-Behaviour (SIB) Study: examining mechanisms underpinning self-harm in children with autism and intellectual disability
Funder: Medical Research Council

Abstract: Self-harm occurs in 50% of children with autism and intellectual disability (ID). These behaviours are severe, persistent and associated with deleterious consequences for children and their families. Despite poor outcomes, only 0.02% of published autism papers are concerned with behaviours such as self-harm, and therefore understanding of mechanisms underpinning self-harm remains limited. The prevailing model of self-harm in children with autism and ID is derived from an associative learning account. Whilst this model describes observable clinical phenomena in the form of behaviour-contingency relations, it cannot account for child characteristics associated with the presence and severity of self-harm. Hence the likely cognitive and psychobiological mechanisms underpinning self-harm have not been delineated. Our project targets these risk markers, specifically impulsivity and poor sleep, to identify contributory mechanisms and uncover viable preventative intervention targets for this at-risk population. We will recruit a large cohort of children with autism and ID, and contrast performance on novel, robust measures of executive functioning to determine whether fundamental deficits in response inhibition account for the presence and severity of self-harm. We will also apply direct measurement of sleep phenomenology via actigraphy, to model the independent contribution of specific sleep parameters and circadian sleep/wake patterns to the presence, severity and timing of self-harm. Finally, we will apply experimental methods, systematically manipulating sleep to evaluate the mediating contribution of impaired response inhibition to the relationship between poor sleep and self-harm. These studies will extend the existing operant account of self-harm, incorporating cognitive and psychobiological risk markers to increase model precision and highlight targets for preventative intervention.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Social media, Smartphone use and Self-harm in Young People (3S-YP study)
Funder: Medical Research Council

Abstract: Self-harm describes any behaviour where someone causes damage to themselves in response to distress. It is the strongest predictor of suicide, with 40-60% of people who die by suicide having self-harmed in the past. Traditionally, researchers have mainly studied cutting or self-poisoning, rather than burning, scratching or hitting oneself. In epidemiological studies, self-harm is usually recorded from a report to health services, yet this is the 'tip of the iceberg', with most episodes not coming to medical attention. School-based and community studies have relied on individual retrospective reporting of lifetime self-harm, meaning that little is known about the specific timing or nature of non-help seeking self-harm. There has been considerable media speculation that social media has been responsible for a steep rise in young people self-harming, especially teenage girls. However the evidence is limited to associations rather than offering insight into potential mechanisms underpinning a negative effect. We aim to investigate these by prospectively studying 13-25 year olds from both a community and clinical cohort. Our objectives are novel: we will use retrospective social media data to identify vulnerability periods prior to self-harm; prospectively, we will assess whether these social media vulnerability profiles and smartphone use patterns in the times approaching an episode of self-harm, differ from those who do not have such an episode. If a relationship is established we shall explore mediating factors, e.g. sleep problems and bullying. Our methodology is distinct because we are collecting user-generated social media public posts, passive smartphone usage patterns and monthly outcome data about self-harm to investigate the mechanistic links. This grant has been designed in consultation with young people and YoungMinds, the UK leading national charity for mental health of young people. They will work closely throughout to co-produce the research.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: BiomaRkers for AnorexIa NErvosa and autism spectrum Disorders- longitudinal study
Funder: Medical Research Council

Abstract: Aims: The proposed study aims to make fundamental discoveries in the field of eating disorders by accelerating understanding of the mechanisms underpinning illness maintenance in anorexia nervosa (AN). Objectives: Utilising a high-quality database of multimodal baseline data, we will examine longitudinal changes in social-emotional and cognitive processing in young people with and without AN and those who have recovered from AN. We will additionally investigate longitudinal changes in autistic symptoms and their role in behavioural and brain responses to social-emotional and cognitive stimuli. Finally, we will explore patterns in the longitudinal, multimodal data that predict illness outcome. Design: Longitudinal, mixed methods multi-approach comparative study. Methodology: We will follow-up 160 young people who took part in the initial baseline assessment two years later. The sample includes 70 young people who had a current diagnosis of AN, 70 aged-matched healthy participants, and 20 young people who had recovered from AN when they first completed the baseline assessment. All participants will be female and aged 12 - 25 years. We will conduct the same battery of clinical and behavioural tests and examine longitudinal changes in autistic symptoms, central coherence, set-shifting, and theory of mind. We will also examine changes in the neural systems that underpin implicit responses to positive and negative facial affect, field dependence, and theory of mind. Furthermore, we will apply science driven, Big Data methods to identify patterns in the robust, multimodal data that predict good or poor illness outcome at the 6- and 12-month follow-up points using recurrent neural networks. Using two follow-up time points will enable us to examine the effectiveness and clinical utility of the final model. Our contingency plan of over-recruiting by 10% at the baseline assessment will ensure we will meet the sample size goal at the second assessment point.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Building resilience in adolescence - improving quality of life for adolescents with mental health problems in Colombia (BRiCs study)
Funder: Medical Research Council

Abstract: Although depression and anxiety are leading causes of adolescent disability worldwide, a treatment gap exists, particularly in Low and Middle Income Countries (LMICs), where less than 50% of people access treatment and fewer than 12% receive minimally adequate care. Effective, low-cost and generic interventions are therefore needed. Our aim is to improve adolescent mental health in LMICs by repurposing such an intervention to treat depression and anxiety. To achieve this we will: 1)Repurpose an effective intervention for the treatment of depression and anxiety in adolescence. 2)Assess the feasibility and acceptability of the intervention within two sites in Colombia. 3)Develop an implementation strategy to promote upscale. 4)Engage stakeholders in a participatory arts-based project. We will follow the initial stages of the MRC framework for designing and evaluating complex interventions. Qualitative interviews and focus groups will be used alongside a pilot study to repurpose the existing intervention (DIALOG+) for use with adolescents. The repurposed intervention (DIALOG-A) will be evaluated in a cluster RCT involving 90 adolescents with depression and anxiety. Mental health, quality of life and social situation will be assessed at baseline, 6 and 12 months, and feasibility tested. Interviews will be analysed using the Theoretical Domains Framework and Quality Improvement projects will develop implementation strategies to promote upscale. An innovative arts-based project will capture the voice of adolescents with depression and anxiety to engage stakeholders throughout. If successful, we will develop a low-cost, generic intervention to treat depression and anxiety in adolescence and hence improve health outcomes. Our focus is on two areas in Colombia where adolescents are exposed to stressors such as violence, conflict and deprivation. If effective here, the intervention has the potential to improve adolescent health in other LMICs facing similar issues.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: A Cross-National Study of the Role of Neighbourhood Context in the Mental Health of Refugees
Funder: Medical Research Council

Abstract: This will comprise three main study components: Study 1. Danish Natural Experiment I will use whole population cohort data in Denmark to take advantage of the random allocation of refugee housing - in effect creating a natural experiment. This will allow me to examine the effect of the following neighbourhood characteristics: 1) ethnic density, 2) urbanicity, 3) deprivation and 4) social cohesion on the incidence of the following mental disorders among refugees: 1) psychosis, 2) depression/anxiety, 3) PTSD I have chosen Danish register data as this covers the entire population (including records for 18,000 refugees over up to 27 years), refugee status can be accurately identified and studies have shown comparable neighbourhood effects in Denmark and the UK. I will then examine the overall effects of a dispersal policy on refugee mental health using the Danish data. Study 2. Somali refugees in Lambeth, South East London I will also examine whether relations between the same neighbourhood factors and mental health outcomes in study 1 similarly to Somali refugees in a local UK context. This study will use a dataset comprising GP and psychiatric records linked to census data at LSOA level covering the London borough of Lambeth. Comprehensive recording of country of birth means that this can be used to accurately identify Somali refugees (N=3,200). Study 3. UK local qualitative study I will also conduct a qualitative study investigating the same Lambeth Somali population to: 1) investigate underlying processes that mediate between neighbourhood risk factors and mental health outcomes through qualitative research with a refugee population in a UK context 2) investigate other neighbourhood risk factors not accounted for in the previous analyses and 3) generate further hypotheses to be tested with quantitative data. The results of the UK local qualitative study will therefore inform further analysis of the data collected in study 1 and 2.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Explaining symptom severity, distress and disability in chronic pain: The role of mental defeat
Funder: Medical Research Council

Abstract: Chronic pain is a disabling condition that often does not have a clear underlying pathology. Around 8 million people in the UK are living with severe chronic pain for which long-term management is required. Current psychological interventions tend to focus on symptom management and has so far only demonstrated modest therapeutic impact. Based on previous research in depression and post-traumatic stress disorder, we propose that helping people to live well despite chronic pain requires a better understanding of the deeper impact of chronic pain on people's sense of self and identity. We hypothesise that mental defeat is an important cognitive factor that alters pain responses and predicts symptom severity and the development of distress and disability. We further hypothesise that these effects of mental defeat may be mediated by its impact on people's day-to-day cognitions (attention to pain, perceived stress), emotions (positive and negative mood) and behaviour (physical and social activity, sleep, use of medication). The proposed research will test these hypotheses in samples of chronic pain patients. It has three complementary components, comprising an experiment, a questionnaire and a 1-week experience sampling exercise (ESE). The questionnaire and the ESE each has 3 waves of data collection at baseline, 6-month, and 12-month. This enables the effect of mental defeat in the short and long term to be both evaluated and the performance of a cross-lagged mediation analysis. The ESE will involve in vivo data collection using actigraphy and an online survey to be administered at 3 random times a day, over 7 days. Data collected will be fitted with multilevel models to decipher the day-to-day relationship between mental defeat and the hypothesised mediators. Together, findings of the proposed research will inform treatment development and illuminate the plausible pathways through which mental defeat translates into symptoms, distress and disability.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Identifying mistranslating mRNAs in Fmr1-/y and Syngap+/- models of ASD/ID
Funder: Medical Research Council

Abstract: Exaggerated mRNA translation has been implicated in the neuropathology of two syndromic neurodevelopmental disorders linked to autism and intellectual disability (ASD/ID): fragile X syndrome (FX) and SYNGAP1 happloinsufficiency. This study will utilize Translating Ribosome Affinity Purification (TRAP) and RNA-seq to identify mistranslating mRNAs in key neuron populations in the Fmr1-/y and Syngap+/- mouse models of these disorders. In Specific Aim 1, we will interrogate three neuron populations that are altered in both mutant models and may contribute to behavioural phenotypes: hippocampal CA1 pyramidal neurons, layer 5 medial prefrontal cortical (mPFC) neurons, and basolateral amygdala (BLA) neurons. In Specific Aim 2, we will examine the mRNAs translated in these neurons during fear learning in both mutant and WT. The comparison of differentially translating mRNAs in three key neuron populations during behaviour will allow for a powerful examination of the impact of altered protein synthesis in Fmr1-/y and Syngap+/- models.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Brain, Immunity and Psychopathology following very Preterm birth (BIPP)
Funder: Medical Research Council

Abstract: Infants born very preterm (i.e., born before 32 weeks of gestation) are at high risk of long-term psychiatric illness. BIPP will map the trajectories of brain growth and function that underlies the risk of psychopathology associated with very preterm birth from foetal life to childhood, study the role of genetic and environmental factors, and test the hypothesis that alterations in brain development and psychopathology are caused in part by immune activation in the perinatal period and/or later childhood. The study will be carried out in the largest and most comprehensively phenotyped sample of children who were born very preterm that has been studied longitudinally to age 4-6 years as part of the NIHR-funded Evaluation of Preterm Imaging Study (ePrime). BIPP will collect new cognitive, MRI, immune and psychopathology data in 240 very preterm children at age 9. 120 controls matched 2:1 by age, sex and socio-economic status will be also studied. Firstly, we will provide an unprecedented longitudinal characterisation of brain development with structural and functional magnetic resonance imaging (MRI), and define how this relates to psychopathology, assessed with clinical, dimensional and trait measures. Secondly, we will determine whether peripheral cellular mediators of immune activation, assessed perinatally and in childhood, relate to structural and functional brain alterations and psychopathology. Thirdly, we will integrate these data with other cognitive and psychosocial measures and delineate biologically and clinically meaningful neurodevelopmental trajectories - from foetal life to childhood - to map phenotypic heterogeneity onto alterations in underlying pathophysiology. The results of the study will inform the development and implementation of neurobehaviourally-informed preventative interventions and will facilitate the identification of new pharmaceutical and behavioural targets for improving the mental health outcomes of very preterm children.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: MICA: An experimental medicine model for fast acting antidepressant drug treatment in treatment resistant depression
Funder: Medical Research Council

Abstract: 30% of depressed patients do not respond to conventional antidepressant treatments. However, recent evidence suggests that the NMDA antagonist ketamine can be effective in treatment resistant depression (TRD) with a fast onset of action. Preclinical animal models suggest distinct mechanisms underpinning these clinical effects. First, ketamine has been found to rapidly reduce burst firing of neurones in the lateral habenula (LHb) in rodents, a core site for learning about reward and punishment. Second, behavioural models of emotional memory suggest that while conventional antidepressants affect how new information is processed, ketamine reduces the retrieval of established negative memories. However, these distinct neuropsychological mechanisms have not been tested in humans. A new wave of drug candidates targeting the glutamate system is in development yet there is no current way of screening and selecting the best of these treatments. The current project will use a translational approach to develop an experimental medicine model for fast acting antidepressant drug activity: In study one, healthy volunteers will be randomised to receive one of two doses of ketamine (0.5mg/kg, 0.1 mg/kg) or placebo in a double blind design. The day after dosing, reward and punishment learning (with optimised 7T fMRI scanning) will be assessed using a task robustly associated with LHb function in human participants. Emotional (vs neutral) memory retrieval and consolidation will be assessed using an autobiographical memory task and a prior self-referent encoding task. In study 2, we will test the translation of these effects to patients with TRD, randomised to ketamine compared to placebo. This approach will identify core neurocognitive mechanisms involved in response to fast acting antidepressants in humans, which can be used for target development and screening of novel compounds, achieved via our collaboration with Janssen.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Building resilience and resources to overcome depression and anxiety in young people from urban neighbourhoods in Latin America
Funder: Medical Research Council

Abstract: pression and anxiety are leading causes of youth disability worldwide. Risk factors such as social isolation, conflict, internal displacement and poverty, are common in urban environments. Despite this, many adolescents and young people do not develop either condition and up to 50% who do experience an episode recover within a year. Our aim is to identify resilience factors associated with prevention and recovery from depression and anxiety in adolescents and young people from urban regions in three Latin American countries. To achieve this we will: -Develop appropriate methods of assessing resilience factors in adolescents and young people in Argentina, Colombia and Peru, -Identify resilience factors associated with prevention and recovery from depression and anxiety, -Develop case studies of existing initiatives to amplify these factors, -Engage stakeholders in a participatory arts-based project giving voice to adolescents and young people, -Increase research capacity within Latin American institutions. We will conduct a cross-sectional study of adolescents and young people to assess whether resilience factors differ between 1020 individuals with and 1020 without depression and anxiety to determine which factors may be associated with prevention. The group with either condition will be followed up for one-year in a prospective cohort study to compare those who do and do not recover. Good practice qualitative case studies involving multiple stakeholders will identify existing approaches to amplifying these resilience factors. Our particular focus is on urban environments in Latin America - the most urbanised region in the world, where youth make up a quarter of the population. Identifying resilience factors in this population is crucial for developing new approaches to reduce the burden of common mental disorders. The knowledge generated has the potential to generalise to other Latin American countries and LMICs with rapid urbanisation.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Generation Malawi: A study of family, maternal and childhood mental health
Funder: Medical Research Council

Abstract: A lack of research training, clinical capacity, resources, infrastructure and data in Malawi, greatly limits its ability to attract inward investment and conduct mental health research and healthcare improvements. We propose to directly address this challenge by building clinical research capacity through the coordinated appointment of new researchers and research assistants, a programme of education and dissemination and the development of a population mental health dataset focussed on an area of great unmet need - the mental heath of mothers and their children. We will recruit 5000 mothers prior to delivery of their child from antenatal clinics in Lilongwe and Karonga districts, selected to represent urban and rural populations respectively. We will assess the mental health of mothers before and after birth, and the mental health of their spouses and other family members with a view to identifying the major risk factors for mental health disorders and mitigating variables that promote resilience. We will then examine the impact of maternal and, where possible, paternal mental health on the neurodevelopment of their offspring. We will create a new and highly valuable dataset and bioresource for future genetics and 'omics based research.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: MENTAL HEALTH