NIHRDataInsights/HRCSData huggingface dataset:
Title: Understanding the mechanisms linking cities to psychotic experiences across the lifespan
Funder: Wellcome Trust

Abstract: Urban (versus rural) upbringing is associated with a two-fold adulthood risk for psychotic disorder. My PhD research replicated this association for subclinical psychotic experiences among children and adolescents (e.g., hallucinations and delusions), which are a developmental risk factor for adult psychotic disorders and other severe psychiatric problems. Given that 70% of the world’s population will live in urban settings by 2050, understanding the link between cities and psychotic experiences is an increasingly urgent public health priority. I will investigate this using three UK-population datasets (ALSPAC, E-Risk and UK Biobank), by exploring: 1. The role of environmental features (air and noise pollution) 2. The interplay between environmental and social features (social cohesion and crime) 3. Biopsychological mechanisms (inflammation and cognition) 4. Genetic confounding (drift/selection) This will be among the first research to take advantage of recent developments in high-resolution pollution models. By triangulating three datasets, taking a multilevel, longitudinal and life-course approach, and using advanced statistical methods for mediation and causal inference including causal mediation modelling and the co-twin control design, this research will provide novel insights into the nature of the urbanicity-psychosis association. Identifying modifiable risk factors in the urban environment will ultimately help to improve mental health outcomes in an increasingly urban world.

Lay abstract: Over two-thirds of the world’s population will live in cities by 2050. This trend is concerning, given that urban living is associated with the development of psychotic disorders such as schizophrenia as well as subclinical psychotic experiences such as hallucinations and delusions. However, the mechanisms underpinning this relationship remain unclear. I will examine the roles of neighbourhood environmental features (air and noise pollution), neighbourhood social features (crime and social cohesion), biopsychological mechanisms (inflammation and cognition), and genetic confounding in the link between cities and psychotic experiences across the lifespan. In doing so, I will utilise three large UK studies spanning birth to middle-age, capitalise on recent developments in detailed air pollution models, and apply advanced methods to disentangle causal associations from a range of potential confounds. By identifying modifiable risk factors in the urban environment, this research will help to reduce the harmful impact of city living on mental health.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Applying causal inference methods to investigate the impact of adverse childhood experiences on mental health
Funder: Wellcome Trust

Abstract: Children exposed to abuse, neglect, and dysfunctional home environments (e.g., parental substance abuse, mental illness, domestic violence) have an elevated risk of developing costly and impairing mental health problems. However, as highlighted in a recent report by the UK Science and Technology Select Committee, the extent to which these adverse childhood experiences cause mental health problems is not known. This is because children exposed to adversities are likely to have other genetic and environmental risk factors for mental health problems, which may confound previously observed associations. I will apply causal inference methods to disentangle the effects of adverse childhood experiences on mental health from genetic and environmental confounds. In doing so, I will make use of data from three large population-based cohorts of children from the UK, Sweden, and Norway, with measures of adverse childhood experiences, mental health, and potential confounding factors (including genetic data). By examining whether findings converge across different causal inference methods with different assumptions, I will be able to draw more confident conclusions about the effects of adverse childhood experiences on mental health. In turn, the findings will indicate the extent to which interventions targeting adverse childhood experiences could prevent children from developing mental health problems.

Lay abstract: One in two adults in the UK report having experienced abuse, neglect, or dysfunctional home environments (e.g., parental substance abuse, domestic violence) in childhood. Many children who experience these adversities develop mental health problems. However, it is not known whether such adverse childhood experiences cause mental health problems, or whether the associations are better explained by other factors, such as poverty or genetic risk. I will investigate the impact of adverse childhood experiences on mental health problems. To do so, I will apply innovative statistical techniques that disentangle the effects of adverse childhood experiences from other factors, using data from large studies of children from the UK, Sweden, and Norway. I will compare findings across different statistical techniques to draw confident conclusions about the effects of adverse childhood experiences. The findings will indicate whether interventions targeting adverse childhood experiences could help prevent children from developing mental health problems.

Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Using multimodal normative modelling to predict clinical outcomes in early psychosis
Funder: Wellcome Trust

Abstract: Individuals at the early stages of psychosis already suffer from neuroanatomical, neurofunctional and neurocognitive alterations. However, it is not clear how these alterations interact with each other and, more importantly, how this interaction may help predict who will become unwell. The aim of the proposed study is to uncover previously hidden relationships between brain anatomy, function and cognition that can improve our understanding of the first signs of the illness and help predict illness trajectory at the individual level. This will be achieved by triangulating, for the first time, data fusion, machine learning and a unique longitudinal dataset of individuals at the prodromal stage or with a recent first episode of psychosis. This combination of methods will allow me to address three main objectives: 1) identify previously unknown relationships between anatomy, function and cognition in healthy individuals; 2) develop a model that captures the normative pattern of these hidden relationships and determine by how much each patient deviates from this pattern; 3) use these deviations to predict each patient’s longitudinal clinical outcomes. I will also develop an open access tool that allows non-expert researchers to perform data fusion on their own data. Keywords: psychosis, data fusion, machine learning, outcome prediction.

Lay abstract: Background: Individuals at the early stages of psychosis already suffer from alterations in their brain anatomy and function, and behaviour (e.g. cognitive skills such as memory and attention). However, it is not clear how these changes interact with each other and, more importantly, how this interaction may help predict who will become unwell. Approach: In this study, I propose to address this issue in three main steps. First, I will identify previously hidden brain-behaviour relationships in healthy individuals. Second, I will develop a model that captures the normative pattern of these brain-behaviour relationships and estimate by how much each individual patient deviates from this pattern. Third, I will then use these deviations to make predictions about each patient’s illness course. Impact: Findings from my study will help to better understand brain-behaviour changes in psychosis and how we can use this information to bring personalised care to psychosis patients.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Testing the role of physical activity in promoting resilience against stress-related psychopathology among young people
Funder: Wellcome Trust

Abstract: Stress-related psychopathology (e.g. depression and anxiety) affects one in eight children in the UK. It is therefore crucial to identify modifiable protective factors that can promote mental health in young people. Physical activity is a promising target for the prevention of depression and anxiety. However, the extent to which it can reduce the burden of mental disorders in young people is not known. This is due to the breadth of environmental, social, and genetic factors that could confound the relationship between physical activity and psychopathology. Furthermore, it is unclear whether physical activity can promote resilience to psychopathology in children who are at higher risk by virtue of genetic liability or adversity. I will apply cutting-edge causal inference methods, such as G-methods, Mendelian randomisation, and twin designs, to test whether physical activity can promote resilience against the development of stress-related psychopathology, using data from large population-based cohorts of children from the UK, Netherlands, Norway, and Finland. Triangulating evidence from multiple analytical approaches will allow me to strengthen causal inferences from observational data and minimise potential biases associated with each method. In turn, the findings will indicate whether interventions targeting physical activity are likely to hold promise to prevent stress-related psychopathology.

Lay abstract: Mental health problems such as depression and anxiety affect one in eight children in the UK. Physical activity is associated with better mental wellbeing. However, it is not known whether engagement in regular physical activity can prevent the emergence of mental health problems in children, or whether this relationship is better explained by other genetic and/or environmental factors.I will apply cutting-edge statistical methods to elucidate what effect physical activity can have on preventing the development of mental health difficulties in young people, and disentangle its effects from other risk and protective factors. To do this, I will use data from large studies of children from the UK, Netherlands, Norway, and Finland.By comparing results across different studies and statistical ways of analysing the information, I will draw more confident conclusions regarding whether interventions targeting physical activity could help to reduce the burden of mental health problems among children.

Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Children’s Health in London and Luton (CHILL): impact of London’s Ultra Low Emission Zone on brain development in schoolchildren
Funder: Barts Charity

Abstract: Air pollution impairs children?s brain development, increasing risk of behavioural and mental health problems, and harming life chances. We urgently need to find out whether improving air quality can prevent harm to the developing brain. Currently both national and local government policies aim to reduce traffic pollution; of which the most ambitious is London?s Ultra Low Emission Zone. In this study The team will exploit these interventions to address whether reductions in traffic improve various indictors of how well children?s brains work: from response time, to problem solving and memory recall. In addition, they will look at general mental wellbeing, such as feelings of isolation or anxiety to see how these are affected by poor air quality. The COVID-19 lockdown has also produced an unprecedented reduction to traffic pollution and therefore there has never been a better opportunity to address this question.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: MENTAL HEALTH
Title: Temporal Aspects of Gaze Perception in Autism
Funder: Wellcome Trust

Abstract: In our everyday life, the ability to perceive the occurrence and duration of brief mutual gaze interactions provides us with essential social cues. The human eye, with its great prominence of a white sclera against a dark pupil, seems to provide an optimal cue for this task, the importance of which is underlined by the existence of dedicated brain mechanisms that are tuned to the direction of other's gaze. Individuals diagnosed with Autism Spectrum Disorder (ASD) have been reported to struggle with tasks based on gaze information and, in particular, with the detection and interpretation of gaze direction. However, their ability to estimate gaze duration has not been studied yet. In this project, we aim to conduct a systematic behavioural and electrophysiological investigation of the temporal aspects of gaze interactions in ASD and neurotypical participants. We intend to measure duration discrimination for brief intervals containing gaze stimuli, and, simultaneously, record eye-movements and event-related potentials (ERPs). The analysis of these data will allow us to test the existence of a predictive relationship between the autistic traits and changes in gaze time perception and to decode perceived duration from ERP recordings using multivariate pattern analysis.

Lay abstract: Our ability to estimate the duration of brief gaze exchanges is central to many social interactions. For instance, when a young man catches a girl’s eye at a party, the duration of eye contact signals mutual interest. Changes in the context, in the involved actors, or in gaze duration, though, could convey a different social meaning (threat, for example). Individuals diagnosed with Autism Spectrum Disorder (ASD) have difficulties in exploring a face and appropriately reciprocating eye contacts. While their impaired performance in judging gaze direction has been extensively reported upon, the study of how they perceive gaze duration has not been approached yet. Here, we aim to investigate the temporal aspects of gaze interactions in ASD and neurotypical participants. Analyzing their gaze duration estimates and exploring their brain correlates might lead to a new theoretical framework for the study and treatment of this and other conditions involving impaired social interactions.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MENTAL HEALTH
Title: ‘The Last Taboo of Motherhood?: Postnatal Mental Disorders in Twentieth-Century Britain’
Funder: Wellcome Trust

Abstract: Around 1900 a new classificatory system appeared to eliminate puerperal insanity from the psychiatric canon. However, as this project will illuminate, far from disappearing from psychiatric practice, mental hospital admissions under this category actually increased, while maternal mental illness was frequently drawn on in constructing defence pleas in infanticide trials. Exploration of postnatal mental illness offers a superb opportunity to understand the relationship between psychiatric theory and practice across the twentieth century, how psychiatric categories were defined, understood and implemented, and how they both adapted to and helped create new service provisions and treatments. The project will also explore how broader social and cultural factors, including attitudes towards motherhood and women’s changing status, especially in relation to their alleged bodily and reproductive autonomy, was reflected in interpretations of postnatal mental illness. Existing at the ‘borderland’ of psychiatry and obstetrics, the project will investigate the energetic and on-going debates on causality, that became increasingly complex with the involvement of an expanding range of health professionals and campaign organisations in the second half of the century. Finally the project will explore how public and media responses and the experiences of sufferers can enhance our understanding of postnatal mental illness in the past.

Lay abstract: The shocking effect of maternal mental illness was highlighted in Louis Theroux’s 2019 BBC documentary on puerperal psychosis, which described new motherhood potentially as ‘a time of extreme psychiatric difficulty’. Celebrity accounts, magazine articles and books describing individual and terrifying journeys through these conditions highlight their devastating impact on new mothers and their families. 10-15% of childbearing women develop postnatal depression and one in 1,000 women the more extreme symptoms of postpartum psychosis. Despite increasing acceptance, postnatal mental illness now, as in the past, is perceived as a challenge to the very essence of motherhood that in some cases risks the life of the newborn. This project examines on-going debates on understanding and treating these disorders across the twentieth century in medical and legal practice, and in public and media responses, also questioning how the experiences of sufferers can shed new light on the relationship between motherhood and mental illness.

Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Prediction of Adolescent meNtal healTH from Electronic health Records (PANTHER)
Funder: Wellcome Trust

Abstract: Many people with depression or anxiety experience their first episode in adolescence. There is evidence that major episodes of these common mental disorders can be prevented or mitigated by early intervention. Yet this requires identification strategies that are effective and feasible, as well as acceptable to young people, their families and healthcare professionals. Primary care is often the first port of call for many young people with early signs of common mental disorders. Therefore, we will develop a risk prediction tool based on anonymised electronic primary care records from more than 630,000 adolescents, their siblings and parents. This unique tool will integrate both individual and familial risk factors in its prediction. To ensure the tool is acceptable to users, and to inform how it should be embedded in clinical practice we will work with young people, their families and healthcare professionals to get their perspective.

Lay abstract: Many people with depression or anxiety experience their first episode in adolescence. There is evidence that major episodes of these common mental disorders can be prevented or mitigated by early intervention. Yet this requires identification strategies that are effective and feasible, as well as acceptable to young people, their families and healthcare professionals. Primary care is often the first port of call for many young people with early signs of common mental disorders. Therefore, we will develop a risk prediction tool based on anonymised electronic primary care records from more than 630,000 adolescents, their siblings and parents. This unique tool will integrate both individual and familial risk factors in its prediction. To ensure the tool is acceptable to users, and to inform how it should be embedded in clinical practice we will work with young people, their families and healthcare professionals to get their perspective.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: MENTAL HEALTH
Title: Proof-of-Concept for a5-GABAAR PAMs in the treatment of psychosis’
Funder: Wellcome Trust

Abstract: Recent evidence suggests that a part of the brain called the hippocampus is responsible for the increase in dopamine in a different part of the brain, the striatum, known to cause psychosis. Our hypothesis is that by attenuating activity within the hippocampus, we will then be able to reduce the increase in dopamine associated with psychosis. In order to do this, we plan to target the GABA chemical signalling pathway which inhibits nerve cell excitability. More specifically, we aim to increase the inhibitory actions of the so-called &alpha;5-GABAAR protein, which is highly expressed within the hippocampus and is therefore ideally placed to control overall hippocampal activity. In this proposal, we will identify molecules that selectively enhance the function of GABA at &alpha;5-GABAARs and then test representative compounds in an animal model of schizophrenia to see if they do indeed attenuate increased dopamine activity.

Lay abstract: Recent evidence suggests that a part of the brain called the hippocampus is responsible for the increase in dopamine in a different part of the brain, the striatum, known to cause psychosis. Our hypothesis is that by attenuating activity within the hippocampus, we will then be able to reduce the increase in dopamine associated with psychosis. In order to do this, we plan to target the GABA chemical signalling pathway which inhibitis nerve cell excitability. More specifically, we aim to increase the inhibitory actions of the so-called &alpha;5-GABAAR protein, which is highly expressed within the hippocampus and is therefore ideally placed to control overall hippocampal activity. In this proposal, we will identify molecules that selectively enhance the function of GABA at &alpha;5-GABAARs and then test representative compounds in an animal model of schizophrenia to see if they do indeed attenuate increased dopamine activity.

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Developing an E-Mental Health Detection Tool for EarlyStage Psychosis in the Community
Funder: Wellcome Trust

Abstract: Psychosis is a severe mental disorder that involves abnormal experiences and altered behaviour.Although the onset of psychosis occurs in young people, most cases will only be identified later inthe course of illness. The delayed detection is the main cause of significant negative long-termoutcomes.The current proposal will develop an innovative E-mental health detection tool to effectively improvethe identification of young people with emerging psychosis. This tool will be implemented on digitalplatforms including websites, tablets and mobile phones. Young people will be asked to completean online questionnaire and two short online-exercises and will then be invited for face-to-faceassessments to further confirm whether they are experiencing an emerging psychosis. This digitalapproach leverages previous expertise by our research team and it is expected to provide novelavenues to enable the identification of young people with emerging psychosis.

Lay abstract: Psychosis is a severe mental disorder that involves abnormal experiences and altered behaviour. Although the onset of psychosis occurs in young people, most cases will only be identified later in the course of illness. The delayed detection is the main cause of significant negative long-term outcomes. The current proposal will develop an innovative E-mental health detection tool to effectively improve the identification of young people with emerging psychosis. This tool will be implemented on digital platforms including websites, tablets and mobile phones. Young people will be asked to complete an online questionnaire and two short online-exercises and will then be invited for face-to-face assessments to further confirm whether they are experiencing an emerging psychosis. This digital approach leverages previous expertise by our research team and it is expected to provide novel avenues to enable the identification of young people with emerging psychosis.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH