NIHRDataInsights/HRCSData huggingface dataset:
Title: Transdiagnostic cognitive behaviour therapy for eating disorders: efficacy and mechanisms of action.
Funder: Wellcome Trust

Abstract: "Eating disorders" of clinical severity (such as anorexia nervosa and bulimia nervosa) are a cause of substantial psychiatric and physical ill-health. They typically begin in adolescence and often become longstanding. It is well-known that they are difficult to treat and they impose a significant burden on health services. This application is for funds to continue a Trust-funded programme of research on these disorders and their treatment. One major outcome of this research has been the development of the leading treatment for eating disorders (cognitive behaviour therapy for bulimia nervosa), a treatment strongly endorsed by the NHS National Institute for Clinical Excellence (NICE) and other national clinical practice guidelines. Recently, we have developed an "enhanced" form of this treatment (CBT-E) that is designed to be suitable for the full range of eating disorders seen in clinical practice, rather than just cases of bulimia nervosa. Our data suggest that CBT-E is a potent treatment for the majority of these patients. We now propose to study: 1) whether this is a specific effect rather than a non-specific psychotherapeutic one; 2) whether CBT-E is superior to the leading potential alternative treatment; 3) how CBT-E is likely to work; 4) the value of CBT-E in treating those patients who are severely underweight.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Identification of quantitative trait genes in the mouse.
Funder: Wellcome Trust

Abstract: The aim of this proposal is to identify genes that are involved in anxiety and depression, thereby providing insights into the biological processes that give rise to some of the commonest and most disabling diseases. The approach is to use animal models of these conditions and builds on the progress we have made in using outbred mouse populations for gene mapping. Using mice, we have been able to identify chromosomal regions that contain genes involved in a number of common human diseases. In addition to anxiety and depression, we have looked at models of asthma, diabetes and obesity. Our first goal is to find the genes that are involved with models of psychiatric disease, and we will do this by characterizing the genes themselves and using a genetic test of their involvement in the phenotype. We will then determine whether any of these genes are involved in depression and anxiety by testing for their association with these conditions in a large human sample. We will look in more detail at the genetic basis of depression and anxiety in a second large cohort of mice, collecting as before information about genetic susceptibility to asthma, diabetes and obesity in collaboration with other scientists in the Wellcome Trust Centre. This data set will allow us to look at the relationship between gene expression and disease, as well as explore a novel hypothesis about a cause of depression, namely its relationship with the production of new neurons. While my interest is in anxiety and depression, the data we collect will be of value for the investigation of other common diseases. My collaborators in Wellcome Trust Centre will be able to take advantage of the resources we develop to advance their research. Our goal is to develop outbred mice as a tool for the science of systems biology.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Developmental relationships between dyslexia and specific languate impairment
Funder: Wellcome Trust

Abstract: The present proposal aims to clarify the relationships between oral and written language difficulties, to investigate their cognitive bases and environmental correlates, and to use improved knowledge to design a programme of intervention. The study will trace the development of children at family-risk of dyslexia, children with language impairment, and normally developing children from 3-7 years - a critical developmental period during which the foundations of reading are laid down. The study will assess how frequently such children experience reading difficulties and how these relate to underlying language skills. It will investigate how children with SLI resemble pre-school children who go on to be dyslexic and whether it is possible to predict which children will develop reading problems from language and cognitive measures. The study will also investigate the extent to which impairments in grammar and vocabulary growth can be traced to auditory or speech processing difficulties earlier in development. Finally, it will evaluate the efficacy of an intervention to improve the reading skills of children from these groups and provide important information concerning individual differences in response to treatment.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Social Epidemiology of Psychoses in East Anglia [SEPEA] study: disentangling poverty, migration and urbanicity.
Funder: Wellcome Trust

Abstract: This proposal attempts to advance understanding of the social determinants of psychotic disorder in rural areas, where presently little is known. I will use data from two existing studies in East Anglia, which offers a unique and timely population laboratory to conduct this research. Within its population there are marked variations in immigration, poverty and urbanicity. This study seeks to separate out these effects on the risk of psychoses and has the following goals/aims To: 1-Estimate t he incidence of psychoses in East Anglia 2-Determine in this unique population whether the incidence of psychoses varies by: a) age and sex b) ethnicity c) immigrant status and immigration history d) urbanicity e) socioeconomic deprivation and other social characteristics f) combinations of the factors stated in part (e) including whether the risk of psychosis is conditional upon the composition of the populati on in which people live. 3-Understand whether At-Risk Mental States [ARMS] (people who have a high risk of psychoses) also show variation by socioenvironmental characteristics. 4-Develop a tool for health services planning to predict the expected burden of psychotic disorder in a given area based on the findings from (2). These models can then be used to help mental health services plan where resources are most needed.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: MENTAL HEALTH
Title: A machine learning approach to the analysis of psychiatric neuroimaging data.
Funder: Wellcome Trust

Abstract: One in four people will experience mental health problems during their life (World Health Organization). The development of technologies for assisting psychiatric diagnosis and predicting treatment responses is extremely relevant to avoid inefficient treatment and to promote mental health. Neuroimaging techniques provide quantitative measures of brain abnormalities and hence can be used to assist psychiatric diagnosis. However, most neuroimaging studies use approaches that are limited in their ability to characterize differences between groups since they are biased toward detecting group differences that are highly localized in space and do not account for the whole pattern of brain activation or anatomy. This spatially distributed pattern information can be investigated using multivariate pattern recognition methods. The purpose of this research is to develop new pattern recognition approaches for the analysis of neuroimaging data to help the understanding, diagnosis and prognosis o f psychiatric disorders. Key Goals: 1. Development of new computer based techniques for the analysis of brain scans. 2. Development of multi-modal classification integrating data from different techniques (e.g. MRI, genetic data). 3. Validation of the developed approaches using a variety of data sets. 4. Translation of the validated approaches into clinical practice.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH
Title: The childhood adversity and psychosis study (CAPsy) study: Integrating society, psychology and biology to investigate links between childhood adversity and psychosis
Funder: Wellcome Trust

Abstract: People with a psychotic illness often hear voices or hold beliefs that to others seem irrational. These symptoms occur in a number of serious mental disorders, most commonly schizophrenia. Some recent studies have reported a link between childhood abuse and psychosis in adulthood, and this has led some to conclude childhood adversity is a cause of psychosis. However, a number of questions remain. For example, why do so few who experience abuse go on to develop psychosis? We propose to invest igate in detail the relationship between forms of adversity (abuse, adverse home environment, peer bullying) and risk of adult psychosis. We will then investigate whether the likelihood of developing psychosis is even greater if other social, psychological or biological risk factors are present, such as adult social adversity. We will do this by collecting and analysing detailed information about these factors from a representative group of 360 cases with a first-episode of psychosis and 360 h ealthy volunteers selected randomly from the population. The applicants for this study form a large multi-disciplinary team with expertise across all the areas being investigated. The findings will provide important information generally about the causes of psychosis, and will inform prevention and intervention strategies.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: The neural basis of genetic vulnerability to bipolar disorder.
Funder: Wellcome Trust

Abstract: Bipolar Disorder (BD) is a debilitating illness characterised by deficits in emotional and social functioning. Abnormalities of brain function in BD suggest involvement of emotional and reward-related circuitry in the pathophysiology of the disease. Whether these findings reflect genetic components or are secondary to ongoing symptoms or their treatment remains uncertain. Unaffected relatives of people with BD experience subclinical mood instability and similar cognitive deficits to their ill re latives, reflecting genetic liability, but are free of confounding factors such as medication. Understanding whether disruptions of emotional circuitry exist in unaffected relatives should therefore elucidate the neural mechanisms of BD and point to future avenues for early diagnosis and intervention. This study aims to investigate the emotion processing circuitry in individuals with BD, their unaffected relatives and controls using two brain imaging tasks that involve facial emotion processi ng and, separately, memory for emotional scenes. These tasks activate neural circuitry involved in emotion regulation. We believe this will be the first familial imaging study of emotion processing in BD.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: A psychological approach to understanding and treating bipolar disorder: investigating new cognitive mechanisms
Funder: Wellcome Trust

Abstract: Bipolar disorder (also known as manic depression) is chronic and disabling with a high suicide rate. Nevertheless, it is poorly understood. People with bipolar disorder experience extreme mood swings, comprising periods of deep depression and periods of elation (mania). Drug treatment is available but has not proved adequate. Novel therapeutic approaches are required. Cognitive behaviour therapy (CBT), a talking therapy, provides a promising candidate. Where CBT has proved most effective ( e.g. anxiety / eating disorders) it has been developed from an understanding of those psychological processes maintaining the specific problem. The proposed research will examine novel psychological processes in bipolar disorder, specifically mental imagery . This involves seeing our memories in our mind s eye and imagining future events. The applicant has previously shown that imagery (e.g. vividly picturing yourself injured in a car crash) has a more powerful impact on emotion than verbal ideas (e.g. I might be in a car crash ). It is predicted that in bipolar disorder overactive mental imagery leads to extreme emotions and day-to-day mood fluctuations. The proposed research tests this theory, providing information to develop a new form of bipolar-specific CBT. The approach offers clinicians concrete treatment options (imagery techniques) not yet harnessed in this disorder.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Deficits in processing of sensory context associated with schizophrenia.
Funder: Wellcome Trust

Abstract: Schizophrenia affects more than 500,000 people in the UK, but the underlying brain abnormality that causes it remains poorly understood. Key symptoms of schizophrenia (e.g. paranoia) can be understood as a dysfunction of the normal processes that mediate context; patients place too much emphasis on selective sensory input, and take things out of context . The brain deals with context using inhibition (by having neurons turn one another off) and it has been proposed such inhibition may be weaker or even absent in patients with schizophrenia. Healthy people rely on inhibition extensively during visual processing; context can drastically alter the appearance of things, sometimes leading to illusions. Our research has shown that patients with schizophrenia are immune to some illusions making them better at certain tasks, suggesting they rely less on context and have less inhibition. It is unusual and revealing to find a task that patients perform more accurately, and this project examines whether these effects extend to different visual stimuli (e.g. moving patterns), other modalities, (touch) and uses brain imaging to reveal which brain regions are involved. This will help us to understand the nature of the brain dysfunction underlying schizophrenia, which will help us better diagnose the illness.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Medicine, Emotion and Disease in History.
Funder: Wellcome Trust

Abstract: Since Charles Darwin wrote about The Expression of the Emotions in Man and Animals in 1872, we have tended to think of our emotions as hard-wired biological states that humans and other animals have acquired as evolutionary adaptations. Such a view, however, overlooks the fact that our understanding, experience, and expression of emotions all have long and complex histories of their own. 'Medicine, Emotion and Disease in History' is a project undertaken by a group of historians at QMUL, to i nvestigate the ways that theories, experiences, and expressions of passions and emotions have developed in medical contexts over the past five hundred years. The project will aim to discover how passions and emotions have been understood historically as physical or mental phenomena, as signs of health or disease, and as psychological phenomena to be managed, restrained, and controlled, whether by the individual subject, by medical practitioners, or by the state. Over a period of five years, this project will organise seminars, workshops, and a major international conference, and will award two postgraduate students the opportunity to undertake doctoral research in this field. The research group will publish journal articles, monographs, and edited works on these themes.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH
Title: The computational neurobiology of attention.
Funder: Wellcome Trust

Abstract: 1. Work up a plausible model of behaviour in the task, based on the Free Energy Principle and informed by knowledge of cortical structure and neurotransmitter action. 2. Acquire performance and neuroimaging data in the task from normal subjects. Use these data to parameterise and optimize the model, using Bayesian model comparison. 3. Choose one or two psychoactive drugs that are implicated in mental disorder and abnormal task performance in normal subjects and measure performance on this task under these drugs. I will then re-parameterise the model for performance on this drug. The PhD will focus on attention. Patients with schizophrenia seem to be particularly deficient in attentional tasks which involve conflict or identifying which stimulus to attend to (Luck & Gold, 2008; Wang et al., 2005; Maruff et al., 1998). Thus, I will use a modified version of the Posner task (Posner et al., 1978), which introduces conflict, to study this phenomenon. In the Posner subjects are required to foveate a central spot and respond as quickly as possible to the appearance of a peripheral target. The side the target will appear is cued at a fixed interval beforehand. The cue is correct (valid) 80% of the time. Posner found that reaction times to validly cued targets were significantly shorter than to targets which were incorrectly cued. This demonstrated that attention could be moved to salient locations in the absence of gaze shift. Evidence as to the performance of schizophrenic patients in this task is mixed. The choice of this paradigm is based partly on the fact that the groundwork of the modelling has already been done. Moreover, the Posner paradigm yields a wealth of data ? the values parameterising the reaction time distributions to cues with up to three different levels of validity, plus the proportion of correct responses ? which will furnish empirical constraints on key model parameters (e.g., synaptic rate constants and gain). In addition, the cognitive processes engaged by this paradigm are clearly influenced by the pathological process underlying schizophrenia.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Separate and interactive effects of COMT and acute tetrahydrocannabinol treatment on frontostriatral dopamine function.
Funder: Wellcome Trust

Abstract: The frontostriatal dopamine (DA) system is a key modulator of cognitive function. Dysfunction of this system has been associated with many pathological states including schizophrenia, obsessive compulsive disorder, and cognitive decline in ageing. It has been shown that both genetic and environmental factors can alter frontostriatal DA function. The proposed research project focuses on two of these factors, namely a functional polymorphism in the catechol-0-methyltransferase (COMT) gene and the use of cannabis. It aims to investigate whether COMT and t.-9- tetrahydrocannabinol (THC; the primary psychoactive ingredient of cannabis) have separate and interactive effects on frontostriatal DA function. More specifically, I will examine whether COMT and THC have separate and interactive effects on a) behavioural indices known to depend on frontostriatal DA function b) striatal and prefrontal cortex (PFC) DA levels c) striatal and PFC gene expression. This research will provide valuable information about the effects of cannabis and COMT on normal brain function, both separately and in combination. Investigation of the mechanisms underlying this interaction, which is one of the most promising of the proposed gene x environment interactions in psychiatric research, will help to clarify how individual genetic differences might influence responses to cannabis and why some people may be more vulnerable to psychosis and cognitive dysfunction following cannabis use then others.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Risk and protective factors for conduct problems and violence in Brazil and Britain.
Funder: Wellcome Trust

Abstract: Violence is a serious public health problem, causing great harm to victims, and imposing an enormous cost to health services, justice systems, and social relations. Although most studies of violence have been conducted in developed countries, rates of violence in developing countries are much higher, reaching almost epidemic levels in some Latin American countries, such as Brazil. A new cross-national study will compare adolescents in Brazil and Britain to provide, for the first time, robust evi dence on predictors of youth violence in Brazil, and similarities and differences with Britain. The study will use data on the biological, psychological and social development of over 5,000 children in each country. By collecting additional information on violent behaviour in adolescence, novel findings on predictors and causes of violence will obtained in the two countries, providing critical new evidence with which to design prevention programmes.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Wellcome Trust Clinical PhD Programme in International Health at the LSHTM: 'The roles of non-specialist health workers in mental health care provision in developing countries'.
Funder: Wellcome Trust

Abstract: With the significant burden of mental illness in developing countries, the large treatment gap due principally to scarcity of skilled mental health personnel and inequities in their distribution, non-specialist health workers (professionals and non-professionals) (NSHW) are important for task-shifting within mental health care. Growing evidence for NSHWs? use in mental health care highlights the need to systematically examine their roles. India has pioneered decentralised mental health services since the 1970s but so far has had limited success in increasing coverage. Describing programmatic achievements and failures and understanding roles of NSHWs within mental health care are essential for informing policy makers and for building recommendations on effective implementation and sustainability of scaling up community mental health services in India and other low income countries (LICs). This project systematically reviews LIC mental health initiatives, which has not been done before. It explores the history and development of NSHWs? roles in mental health care provision in India through oral and written historical primary source analysis, describes NSHWs current roles through ethnographic observation and interviews and uses Delphi and workshop methods with key international and Indian stakeholders to examine the acceptability and feasibility of non-specialists? roles to inform the development of policies in LICs.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: MENTAL HEALTH
Title: Causal Inference in Observational studies of Cannabis and Tobacco
Funder: Wellcome Trust

Abstract: 1) Examine associations between adolescent substance abuse (age 13- 17) and environmental factors including educational outcomes, S.E.S. and adolescent behaviours. Analysing the differentiation of academic achievement due to social class and evaluating the causal pathway for substance abuse. 2) Investigate the interaction between cannabis and tobacco and their association. 3) Complete a comprehensive Genome-Wide Association Study (GWAS) analysis for cannabis and tobacco phenotypes. Investigating possible genetic loci for use as an instrumental variable (IV). 4) Investigate causation using a Mendelian Randomisation (MR) approach using IV's from my GWAS.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH