NIHRDataInsights/HRCSData huggingface dataset:
Title: Depression Genetics in Africa (DepGenAfrica)
Funder: Wellcome Trust

Abstract: Background: rapid advances in our understanding of psychiatric disorder genetics within European ancestries are leading to mechanistic insights, more accurate risk stratification and stronger causal inferences, but there is growing concern that these findings may not generalise to African ancestries and those who reside in low and middle income countries. We need to urgently address this knowledge gap if we are to reduce growing health disparities. Vision: drawing on the substantial strengths of the UK Psychiatric Genomics Consortium (PGC) and a network of African investigators, we will develop processes for rapid sample collection and address critical scientific and clinical questions about the genetic architecture of depression in non-European populations. Research plans: using state-of-the-art ancestry-aware genetic methods, we will address whether the genetic architecture of major depressive disorder in different African countries is similar and whether it mirrors that of European ancestry populations. We will develop a network of UK and African partners in the best clinical research practices. We will adopt a pragmatic approach to data collection and analysis through a combination of new sample collections and genotyping and analysing existing samples; building capacity at each stage of the research process.

Lay abstract: Understanding the combination of genetic and environmental risk factors that cause depression is key to developing new therapeutics and to relieving the increasing burden they place on societies and economies worldwide. While the last decade has seen huge advances in depression genetics, these have been in European and East Asian populations only. We urgently need to develop a better understanding of depression genetics in Africa populations to correct this inequity. Our consortium will study depression genetics and environmental/social risk factors in three different African countries, comparing the results with studies of African ancestry populations in Europe and the USA. While deepening psychiatric genetics expertise across Africa, we will apply the latest advanced statistical genetics methods to find genetic risk factors for depression that are specific to African populations and that are shared across populations.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MENTAL HEALTH
Title: Mental health in the moment: A developmental study of adolescent mental health and its influences in daily life
Funder: Wellcome Trust

Abstract: Adolescence is both a critical period of development for mental health and a time of rapid change. To illuminate the evolving influences on, and manifestation of, mental health issues over this period thus necessitates creative methodologies that capture rich data on multiple timescales. The current study will use a multi-timeframe measurement burst accelerated cohort study to capture rich data on the daily life experiences of adolescents in relation to their mental health over 5 years. This will allow us, for the first time, to understand how daily life experiences coalesce into long-term changes in mental health, as well as how long-term developmental changes impact the daily life manifestations of ,and proximal influences on, mental health issues. This can inform better preventive interventions by identifying new and optimal ‘daily life’ targets at different developmental stages. It can also provide invaluable information for the further development of promising and increasingly popular ecological momentary (smartphone-based) interventions at these developmental stages.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MENTAL HEALTH
Title: A major barrier to innovation in treatment and care for people with psychosis in lowincome countries is the absence of rigorous epidemiological research into the aetiology, presentation, social context, associated physical health conditions and early course of psychosis.
Funder: Wellcome Trust

Abstract: Through SCOPE, we will produce high quality, contextual evidence and use it to designinnovations in detection and treatment, to improve the lives of people living withpsychosis in a low-income country.Our key goals are to:1. determine the rate of new cases of psychosis in rural and urban settings inEthiopia; identify possible risk factors for onset; and characterise the needs ofpeople with psychosis and the factors that affect early course and outcome.2. use this evidence to co-develop innovations to improve early detection andoptimise the recovery of people with psychosis. The innovations will beapplicable to rural, urban and homeless populations in Ethiopia, with potentialgeneralisability to other low- and middle-income countries.We will pilot test interventions, develop strategies to overcome implementationchallenges and identify key intervention components to inform adaptation for othercontexts.

Lay abstract: In SCOPE our key goals are (1) to determine the rate of new cases of psychosis in rural and urban settings in Ethiopia; identify possible risk factors for onset; and characterise needs of people with psychosis and factors that affect early course and outcome; and (2) use this evidence to co-develop bottom-up innovations to improve early detection and optimise recovery of people with psychosis that are applicable to rural, urban and homeless populations in Ethiopia, with potential generalisability to other low- and middle-income countries.In the formative phase of the project (year 1), we will develop a detection strategy and explore perspectives of people with lived experience of psychosis on the concept of recovery. In years 2-4 we will conduct an epidemiological study to identify people with untreated psychosis in rural districts in south-central Ethiopia (240 people with psychosis/600,000 population screened) and a sub-city of Addis Ababa (150 people with psychosis/400,000 people screened), and approximately 50 people with current or recent experience of homelessness. We will assess mental and physical health, social and economic status, and follow up participants for one year. In years 3-5 we will work with key stakeholders, including people with lived experience of psychosis, to incorporate emerging evidence into development of interventions to improve early detection and recovery. We will pilot test interventions for rural settings in a feasibility randomised controlled trial (n=75); and models for urban and homeless populations in uncontrolled pilot studies (each n=15). Implementation research methods will facilitate adaptation to other LMICs.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH
Title: Preventing violent crime and suicide in mental illness
Funder: Wellcome Trust

Abstract: The risks of violent crime and also suicide are increased in people with schizophrenia-spectrum disorders, bipolar disorder, and depression. Although we understand more about the underlying causes for these risks, translating this knowledge into improvements for patient care requires more research into identifying high risk groups and clarifying what treatments might prevent these outcomes. This fellowship aims to investigate how to improve the assessment and reduce the risks of violent crime and suicide in individuals with mental illness. The approach I will take is to use large datasets that have collected real-world information on patients over many years, and use research designs that account for socio-demographic and other background factors that differ between patients and others. As part of this, I will aim to develop reliable methods of assessment that could lead to effective interventions. I will also study what medications alter risks of violent crime and suicide in these patient groups, and also the effects of psychological and behavioural interventions in mentally disordered persons under community criminal justice supervision. Ultimately I would like to test whether these new approaches prevent violence and suicide in psychiatric patients, and will investigate in this programme whether such a trial is feasible.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Common Variant Genetics of Autism and Autistic Traits (GWAS) Consortium
Funder: Wellcome Trust

Abstract: Autism is a life-long developmental condition with a prevalence of approximately 1%, and heritability estimates of between 64-92%. It is polygenic, with variants across the frequency spectrum (from rare to common) contributing to risk. Considerable progress has been made in identifying rare variants in autism, but the largest genome-wide association study (GWAS) of autism (18,000 cases, 28,000 controls) identified only five loci associated with autism, compared to 179 in schizophrenia (40,000 cases, 65,000 controls). Polygenic scores account for 2.45% of the variance in autism, despite 30-50% of the variance in risk for autism being attributable to common variants, suggesting many more common variants remain to be found. Additionally, autistic traits are normally distributed in the general population, but there is no well-powered GWAS of autistic traits. The proposed research aims to accelerate the discovery of common, low frequency, and copy number variants in autism and autistic traits. Specifically, we will: (1) Establish a UK-wide Autism Biobank (N = 10,000 cases), with links to electronic health records and who can be recalled by genotype; (2) Conduct a GWAS of autism in 100K cases from around the world; and (3) Conduct a GWAS of autistic traits in the population in 250K individuals

Lay abstract: Autism is a lifelong developmental condition and approximately 1% of the population are thought to be autistic. It is largely genetic, and between 400-1000 genes are thought to contribute to autism. However, fewer than 100 genes have been identified that are linked to autism. We propose to accelerate gene discovery by collecting DNA samples from 10,000 autistic individuals in the UK and their immediate families. We will combine this genetic information with genetic information from 90,000 additional autistic individuals already ascertained across the world. This large-scale resource will enable us to identify several genetic variants that contribute to the development of autism. This information will allow us to better understand the biology of autism, improve on existing methods for diagnosing autism, and investigate if there are genetically-defined subgroups within autistic people.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Promoting mental health and building resilience in adolescence: Investigating mindfulness and attentional control.
Funder: Wellcome Trust

Abstract: Mental health problems most commonly start during adolescence. Major depression carries the largest potential burden in terms of years lived with disability and this proposal aims to determine how best to prevent it. It is based on the hypothesis that depression, and co-occurring behavioural problems, in part represent a failure to exercise top-down executive control, impairing the ability to recruit effective problem-solving skills in the face of emotional distress. Mindfulness training (MT) has been seen to be highly effective in adults. This Strategic Award addresses the question: Has mindfulness training (MT) in adolescence the potential to shift the secondary school-age population away from psychopathology and towards improved mental health by addressing key processes of mental regulation and executive control that operate across the spectrum of risk/resilience? Two of three interlinked research themes' examining mechanisms (Theme 1) and implementation (Theme 2) have been funde d. This invited resubmission addresses Theme 3, namely a large-scale cluster randomised controlled trial to investigate the effectiveness and cost-effectiveness of MT in schools.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: An AMPA receptor positive allosteric modulator for the treatment of cognitive impairment associated with schizophrenia
Funder: Wellcome Trust

Abstract: First-in-Human, Phase 1 safety, tolerability, pharmacokinetic and pharmacodynamic/target engagement studies of MDI-478, a positive allosteric modulator (PAM) of the &alpha;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype of ionotropic glutamate receptor (AMPAR). The aim is to demonstrate that MDI-478 is safe and well-tolerated and demonstrate pharmacodynamic effects and/or target engagement sufficient to support Phase 2 efficacy studies”.

Lay abstract: This proposal is a request to fund First-in-Human, Phase 1 safety, tolerability, pharmacokinetic and pharmacodynamic/target engagement studies of MDI-478, a positive allosteric modulator (PAM) of the &alpha;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype of ionotropic glutamate receptor (AMPAR). We aim to demonstrate that MDI-478 is safe and well-tolerated and demonstrate pharmacodynamic effects and/or target engagement sufficient to support Phase 2 efficacy studies. More specifically we intend to: • Synthesise 3 kg of active pharmaceutical ingredient (API), manufactured according to Good Manufacturing Practices (GMP) to support clinical trials. We will then conduct a three-part (Parts A, B and C) Phase 1 study in healthy volunteers including: • Part A: A six (possibly seven)-cohort single ascending dose (SAD) study over an estimated range of 3-120 mg total dose, with each cohort containing 6 drug- and 2 placebo-treated subjects. • Part B: A four (possibly five)-cohort, up-to-28-day multiple ascending dose (MAD) study using doses selected based upon the SAD, again with a 6+2 cohort design. A single cohort will also undergo CSF sampling. • Part C: A single cohort (n=20) to receive placebo or one of two doses of MDI-478 in a three-way cross over design using magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), mismatch negativity (MMN) and cognitive testing as exploratory measures of target engagement. • The primary endpoint will be adverse events. • Secondary endpoints will include: ◦ pharmacokinetics. ◦ target engagement measures, including drug-related changes in MEG, fMRI, MMN signals and/or cognitive performance. The output of this project will be documentation demonstrating that MDI-478 is a Phase 2-ready drug.

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: An innovative AI application for the betterment of individuals’ productivity and wellbeing, improving individuals’ self-reported anxiety by 37%
Funder: Innovate UK

Abstract: Talk It Out (TIO), led by Chris Baréz-Brown and Ross Faulkner, is a UK health tech SME developing an app to boost people's productivity and wellbeing. Poor mental health affects millions of people around the world and has increased in the UK since the start of the COVID-19 pandemic; its cost to employers has risen to £35B, but efforts to address it pay generous dividends. TIO improves both the wellbeing and the productivity of its users, harnessing AI to help them understand their subconscious thoughts and emotions which gives its users a choice on _how_ to deal with them, putting them in control of their mental & emotional wellbeing.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: MENTAL HEALTH
Title: University of Northampton (The) and MyCognition Ltd
Funder: Innovate UK

Abstract: To develop, test and launch an innovative digital tool to support cognitive decline in ageing populations. The software application can be used on a persons smart device and will assess and enhance cognitive functioning and factors such as wellbeing and recovery.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH
Title: Learning to hear again: Brain mechanisms supporting perceptual learning of degraded speech
Funder: The Academy of Medical Sciences

Abstract: My aim is to understand the brain mechanisms supporting perceptual learning of degraded speech, with the long-term goal of improving prognosis and rehabilitation in cochlear implant listeners. Here I propose a new paradigm to investigate perceptual learning, using state-of-the-art Temporal Response Function analysis of electroencephalography (EEG). Over several days, normal hearing listeners will be trained to understand one of two forms of speech differing in which acoustic features are degraded (spectral versus temporal modulations). I will test the hypothesis that perceptual learning is the result of changes in neural sensitivity to spectral and temporal modulations in degraded speech. If successful, this project will establish a new brain mechanism for speech perceptual learning.

Lay abstract: Worldwide, more than 300,000 deaf people have a cochlear implant, and for many, it is a life changing device. A cochlear implant restores hearing by sending sound directly to the brain as electrical signals. For someone who could hear before their deafness, listening to speech through an implant is often very different from what they remember. This is because an implant cannot recapitulate the performance or functional ability of the ears. As a result, the sounds transmitted to the brain by an implant are very degraded. After implantation, the brain gradually learns to interpret degraded speech. However, for every listener who can understand speech from the implant without lipreading, there is another who cannot. This suggests that some listeners find the learning process more difficult than others. I want to know why this is and develop better tools for prognosis and rehabilitation programmes. But to do so, we need a better understanding of how the brain learns to understand degraded speech. I will simulate hearing through cochlear implants by using computer software to degrade speech and presenting this speech to normal hearing adults. I will then record brain activity safely using sensors placed on the head. By using state-of-the-art statistical methods, I can measure the brain’s sensitivity to different speech sounds as listeners learn to understand degraded speech. This project will be the first to test my hypothesis about the mechanism by which the brain changes its sensitivity to different types of sound so as to better understand degraded speech.

Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Antecedents of suicide, suicidal ideation, and self-harm for young people with social services involvement: a mixed-methods study
Funder: The British Academy

Abstract: Understanding the antecedents of suicide, suicidal ideation and self-harm among young people is an important public health priority. In the general population, these issues are associated with experiences of adversities, including socioeconomic deprivation and mental ill-health. Yet suicide, suicidal ideation and self-harm are alarmingly understudied in young people with social services involvement, a population facing particular adversity. Using a mixed-methods approach, I will examine the risk and the protective factors for suicide, suicidal ideation, and self-harm among young people with social services involvement. The project will involve three work packages: i) an umbrella review of evidence addressing antecedents of suicide, suicidal ideation and self-harm among young people, ii) interviews with young people with experience of social services intervention (n=25), iii) quantitative analysis of administrative records. All three work packages, and associated academic and media dissemination activities, will be co-produced with experts-by-experience of social services and mental health services involvement.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;7.1 INDIVIDUAL CARE NEEDS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: MENTAL HEALTH
Title: DALIP: Database of Acquired Language Impairment Profiles – a resource for exploring the nature and impact of language processing difficulties in adults with neurological impairments
Funder: The British Academy

Abstract: This project aims to build capacity for research into acquired language impairments. Neurological damage (e.g. stroke or brain injury) causes life-long communication difficulties for one-third of survivors. These difficulties are unique to each person, and change as the person recovers. This makes them complex to understand. In addition, it is often difficult to recruit people into research studies, as their communication difficulties makes them hard to reach. This project will grow and maintain a research panel and database of behavioural data for a large sample of individuals with speech, language and communication impairments following neurological damage (aphasia). Anonymised data will be shared via a web-resource to open opportunities for data mining by scholars from different disciplines. A research panel accessible to other research groups in the UK will contribute significantly to overcoming the challenge of recruiting a population that can be hard to access.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH
Title: The Cognitive Correlates of Psychopathic Personality Traits
Funder: The British Academy

Abstract: Psychopathy is often associated with inalterably dangerous character traits. The scientific literature demonstrates, however, that a more useful framework in which to think about psychopathy is as a constellation of personality traits that are normally distributed in the population, which are characterised by three constructs: disinhibition, boldness, and meanness. Early models focused on deficiencies in emotion processing while current research attention focuses on attention-based deficiencies associated with psychopathic personality traits. The current project aims to develop a deeper understanding of the nature of attentional processing associated with the psychopathic personality trait. Specifically, we aim to determine whether variation in psychopathy is associated with differences in associative learning and the ability to utilise contextual cues from the environment. This research is essential to understanding the cognitive basis of individual differences in personality traits and to lay the groundwork for the development of novel cognitive interventions.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Do the effects of alcohol intoxication compromise face perception?
Funder: The British Academy

Abstract: Alcohol consumption is a common feature of social, sporting and cultural events in many societies. The detrimental effects of acute alcohol intoxication on attention and cognition, and their subsequent consequences (e.g. for driving) are well known. However, it is less well understood how alcohol may affect the psychological processes underlying face perception, despite this being fundamental to many of our social interactions. More empirical evidence about alcohol’s effect on face perception is necessary. The proposed research will investigate the effect of alcohol on basic processes in face perception, using an experimental, lab-based protocol. Two experiments are proposed which aim to compare face processing between alcohol intoxicated and placebo participants, and which utilise well established tasks from the face processing literature. The findings are expected to contribute to our better understanding of how face perception may be affected by alcohol intoxication and will be relevant to various contexts including eye-witness testimony.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH