NIHRDataInsights/HRCSData huggingface dataset:
Title: Identification of genetic risk factors and assessing causality of modifiable exposures in adolescent depression.
Funder: Wellcome Trust

Abstract: The overall aim of my research is to investigate causal risk factors associated with adolescent depression. My research will first aim to investigate genetic risk factors for aadolescent depression through a combination of genome-wide analysis aapproaches. Next, I intend to investigate environmental risk factors for adolescent ddepression using a Mendelian randomisation approach. Finally, I will also use DNA methylation data to investigate whether risk ffactors exert their effects through epigenetic mechanisms.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Life course influences on suicidal behaviour in Low and Middle Income (LAMIC) countries: a cohort study based on 53,000 households in Sri Lanka.
Funder: Wellcome Trust

Abstract: My research will investigate the association of socioeconomic positioning (SEP) and suicide risk in low and middle income countries in Asia, by using Sri Lanka as a case study. The research will use data that is being collected as part of a large randomised control trial being conducted in the North Central Province of Sri Lanka. The data from this trial will be analysed both cross-sectionally and longitudinally to investigate associations of SEP measures and suicide. The household data from the cross-sectional survey has been geocoded and therefore I will be able to look at the effect of area levelSEP measures in relation to individual suicide risk, in particular investigatethe importance of status inconsistency. A key goal is to try and gain a betterunderstanding on how SEP is related to different aspects of the suicidal pathway, as this will help in our understanding on how suicidal behaviour develops.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Contribution to support for M Zaher Shehab - PhD study "analytical techniques to enhance harm reduction advice to users of crack cocaine".
Funder: Wellcome Trust

Abstract: The aim of our research is to establish that profiling illicit crack cocaine samples can make a contribution to reducing the associated hmm to the health of users. Different cutting agents are used to increase the bulk of cocaine samples, some agents mimic the properties of cocaine, but mainly they are cheap and readily obtainable. However, the cutting agent can be harmful to health, e.g. phenacetin causes renal damage. Quantifying the ratios of cocaine to impurities, in a collaboration with a drugs service and the police, may contribute to solving some of the many problems from which addicted users suffer. Samples of crack cocaine seized by police in Swindon, UK, were examined by a range of analytical methods: high performance liquid chromatography (HPLC), high performance thin layer chromatography (HPTLC), gas liquid chromatography (GLC), nuclear magnetic resonance (NMR) and infra-red (IR) spectroscopy, and mass spectrometry (MS). In addition to quantifying the cocaine content and varied from 4% to 80% with a mean of around 40%. NMR analysis showed that phenacetin was present in about 80% of samples: other contaminants identified were benzocaine, glucose and mannitol. NMR spectroscopy, IR spectroscopy, MS and HPTLC all provide visual bar-code-like fingerprints that can be incorporated into local harm reduction messages that may be useful in conveying an impression of contamination to drug service personnel or to drug users, reinforcing the message and leading to harm reduction.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Using human induced pluripotent stem cells (iPSC) and iPSC-derived neurons to explore cellular phenotypes associated with schizophrenia.
Funder: Wellcome Trust

Abstract: Schizophrenia and major mental illness are very common conditions whose underlying causes are imperfectly understood and for which our current treatments are only partially effective. They are known to run in families and some genetic risk factors, including those affecting DLG2 and the so called DISC1 and NDE1 locus, are sufficient to increase risk of major mental illness in those individuals who carry them. It is also known that abnormalities of brain structure and function are closely linked to these genetic factors. The cellular mechanisms underlying these abnormalities and clinical disorders are however still unclear, largely because the human brain is inaccessible. However, it has recently become possible to study brain cells in a dish in the laboratory by reprogramming skin cells (fibroblasts) to become brain cells (neurons and other neural cell-types). I propose to study neural tissue derived from individuals with and without disease-causing genetic factors by reprogramming fib roblasts to become pluripotent stem cells, neural progenitors and neurons which will then be extensively validated and characterized. I will then examine how disease risk is conferred at a cellular level through a series of comparative studies of neural progenitor proliferation, neuronal morphology and physiology as well as synaptic function.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Mechanisms of phenotypic effects of altered 5-HT transporter gene expression
Funder: Wellcome Trust

Abstract: I would like to study the role of altered 5-HTT expression in fear, anxiety and amygdala dysfunction. To do this, I will address two research aims. First, I want to investigate if the behavioural phenotype (altered fear and anxiety) arises from changes that occur during development as a consequence ofaltered 5-HTT expression. I will mask the 5-HTT genotype in neonatal mice by SSRI treatment or by depleting 5-HT levels. If the behavioural changes do not occur, they must result from changes in development rather than from maintained changes in 5-HTT expression. Second, I want to explore changes in amygdala function in 5-HTT KO compared to5-HTT OE and wild-type mice, both with and without neonatal exposure to SSRI treatment/5-HT depletion. I will look at haemodynamic and oscillatory responses to aversive cues, and at signalling of 5-HT neurons projecting to the amygdala in vivo.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Social context and the development and outcome of psychotic symptoms in the general population. .
Funder: Wellcome Trust

Abstract: Psychotic illnesses like schizophrenia are more common in cities, but understanding of the reasons why is limited, partly because psychosis is a rare condition. By looking at the larger population with psychotic symptoms(rather than the full disorder), researchers can investigate causal factors more effectively, and potentially develop ways of preventing the illness or picking it up earlier. Previous research suggests that how disorganized, and how unequal, your neighbourhood is has an effect on your risk of developing psychotic illness, but whether this is the case for the pre-psychotic state is unclear, and this is what I want to investigate. I plan to do this by using data from a large health survey of community households in South London. This data will be electronically linked to health care records, allowing me to investigate the longer term health outcomes for people with psychotic symptoms The results will help to guide interventions aimed at changing the social environ ment of at-risk people and preventing the development of psychosis.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Drugs and Revolution: Policymaking, Ideology and the Margins of Civil Society in Iran.
Funder: Wellcome Trust

Abstract: The research will encompass the framework of relations among political and social actors with regard to drugs and drug policies, paying attention to the public as well as the private and NGO sectors. It will attempt to describe and define the rationale behind the expansion of civil society organisations working on drug control programmes, in view also of the existing restrictions in other fields not related to drugs. As a result the research could cast light on why the topic of drugs has been pe rceived as less problematic by Iranian law-makers and how the state has agreed to concede considerable leeway of manoeuvre to non-state actors in this field. The hypothesis is that the threat of drugs has brought Iranian policymakers to reconsider the margins of acceptability for civil society organisations and consequently other actors in the public sphere. The state has reformulated the practice of intervention vis vis drugs, while at the same time retaining the monopoly of legitimate coerc ion through Law Enforcement Agencies and the discourse of the War on Drugs. Moreover, by virtue of the direct support to NGOs, the state succeeded in co-opting and neutralising their political leverage, de facto outsourcing treatment services.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: MENTAL HEALTH
Title: Excitatory-inhibitory balance in adolescents at high genetic risk of mental disorder: a study of cortical gamma oscillations and GABA concentrations in 22q11.2 deletion syndrome.
Funder: Wellcome Trust

Abstract: Mental disorders such as schizophrenia, autism and ADHD have overlapping symptoms, often run in families and share environmental risk factors. Recently, studies have shown that genes can influence risk across this spectrum of disorders suggesting that they may have common biological mechanisms One proposed mechanism for the overlapping susceptibility to mental disorders is that risk genes affect how brain cells communicate. In healthy individuals, brain cells activate synchronously in order to process information effectively. Risk genes may disrupt this activity and alter the levels of key chemical messengers (known as neurotransmitters) in the brain. Studying brain activity and neurotransmitter concentrations in people known to be at high-risk of mental disorders may give us new insight into how genes influence psychiatric risk. I plan to study adolescents with 22q11.2 deletion syndrome (22q11.2DS). 22q11.2DS affects 1 in 4000 people and is one of the strongest known genetic ri sk factors for mental disorder. I will use state-of-the-art brain imaging techniques to compare synchronous brain activity and neurotransmitter concentrations between adolescents with 22q11.2DS and their unaffected siblings. I will also investigate whether abnormalities in brain activity and neurotransmitter concentrations are associated with the severity of psychiatric symptoms experienced by these young people.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: The effect of parvalbumin positive interneurons on neural oscillation and episodic memory in novel models of schizophrenia
Funder: Wellcome Trust

Abstract: Schizophrenia is characterised by a broad range of symptoms, any of which are in the cognitive domain. It has been suggested that these symptoms arise as a result of dysfunction within and between multiple areas of the brain. As such,numerous clinical studies have revealed dysfunctional neuronal oscillations schizophrenic patients, across a broad range of frequencies, and in diverse brain regions. Often, these changes in network activity are associated with specific cognitive impairments, such as deficits in episodic memory. Parvalbumin-positive (PV+) GABAergic interneurons are of particular interest, as they are known to play a central role in generating and shaping oscillatoryactivity, and a reduction in the number of these neurons have been reported inboth schizophrenic patients and animal models of this disorder. However, the precise contribution of these neurons to the aberrant oscillatory activity evident in schizophrenic patients remains unclear. By recording electrophysiological activity in novel animal models of schizophrenia, the role of PV+ interneurons in the dysfunctions observed in neural oscillations in various cortical and subcortical areas will be characterised. The effect of the oscillatory dysfunction in various vigilance states, on episodic memory deficits will then be assessed by using a behavioural paradigm.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: CON BRIO: Collaborative Network for Bipolar Research to Improve Outcomes.
Funder: Wellcome Trust

Abstract: Bipolar disorder, or manic depression, is a serious mental illness which is poorly understood and only partially treatable. We are a group of researchers from diverse scientific and medical backgrounds who want to bring new ideas and methods to transform this unsatisfactory situation, and we see a unique opportunity to do so. We will approach the key problems in four linked programmes of work. First, to study in more detail the ups and downs of mood in everyday life, since we think that chronica lly unstable mood underlies the clinical mood swings of the disorder. Second, to see how genes contribute to the mood instability and how they work to affect the risk of the illness. Third, to study how cognitive factors (attention, memory etc) interact with mood instability, and how brain activity (measured by two types of brain scan) underlies these effects. Fourthly, and critically, to find better ways to identify and evaluate new treatments for bipolar disorder, both medication and psychol ogical therapies. Throughout, our priority is to be 'translational', that is, to focus on research with the potential to lead rapidly to outcomes relevant to patients and their families.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Transforming the treatment of schizophrenia: Design & development of AMPA receptor modulators with improved safe profiles as novel drugs for treating the cognitive dysfunction associated with schizophrenia and other CNS disorder
Funder: Wellcome Trust

Abstract: Around 1% of the population will suffer from schizophrenia at some point in their life. Symptoms such as paranoia and/or hearing voices can be reasonably well treated by existing medications. However, these drugs have little effect on the other symptoms (lack of motivation and impaired social function) and impaired cognition, including difficulties with attention, memory and problemsolving that result in a brain fog . These largely untreated symptoms remain a huge barrier to the resumption of a fully functional, normal life for these individuals and are associated with an annual estimated cost in the UK alone of around £12 billion. Nerve cells (neurons) communicate with each other by releasing chemicals called neurotransmitters that interact with proteins called receptors on adjacent neurons. Arguably the most important neurotransmitter in the brain is the amino acid glutamate, levels of which ares. altered in schizophrenia. The actions of glutamate are mediated by several types of receptor ofred which one, the AMPA receptor, is particularly important. Therefore, increasing AMPA receptormory and problemsolving function should compensate for the dysfunction in glutamate neurotransmission and should improve cognitive performance in, thereby revolutionizing the treatment of, d schizophrenia. with an Project goal: To identify a novel, innovative AMPA receptor drug to treat schizophrenianeurons) communicate with each other by releasing chemicals patients.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Chronic irritability in ADHD: examining clinical and genetic links with depression.
Funder: Wellcome Trust

Abstract: Attention-Deficit/Hyperactivity Disorder (ADHD) affects 5% of children worldwide. It is characterised by inattention, impulsivity and hyperactivity, and results in impairment into adult life. ADHD is complicated later by depression. This is important, as those with ADHD and depression have more difficulties than those with ADHD alone. Identifying children with ADHD at risk of developing depression provides opportunity for early intervention. Research suggests that children with chronic irritab ility (frequently losing temper, feeling angry/resentful or easily annoyed) are at increased risk of later depression. Chronic irritability is common in ADHD, but its link with depression is yet to be explored in this group. This project aims to test whether childhood ADHD with chronic irritability is associated with increased risk of adolescent depression, and higher genetic loading for depression. A sample of children with ADHD will be used to compare those with and without chronic irritabil ity, in terms of rates of adolescent depression, family history of depression and genetic loading for depression. Due to the overlap of ADHD with other neurodevelopmental disorders (e.g. Intellectual Disability, Autism Spectrum Disorders) a population sample will also be used to assess whether childhood irritability is associated with adolescent depression in a broader group of neurodevelopmental disorders.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Are diagnoses in psychiatry explanations of their symptoms?
Funder: Wellcome Trust

Abstract: The research project is primarily a work in applied philosophy of science, and brings together the philosophical theory on explanation, causation, inference, and classification. It will use philosophical theory and conceptual analysis to examine diagnostic terms and their relations to their respective symptom clusters in the current diagnostic manuals. The central research question of whether diagnoses in psychiatry are explanations of their symptoms will be approached via four angles. First, I will study the important differences between diagnostic reasoning in psychiatry and in medicine, and what this reveals about the conceptual relations between diagnoses and their symptoms. Second, I will explore whether the definitional connection between psychiatric diagnoses and symptoms is merely a function of the way the diagnoses are picked out, or whether it is more profound. Third, I will examine whether psychiatric diagnoses are more like clinical descriptions in medicine, such as 'acute abdomen', than pathophysiological diagnoses. Fourth, I will examine models of explanation to investigate whether the absence of causal connections between diagnoses and symptoms precludes diagnoses from being explanatory. By elucidating the explanatory status of diagnostic categories in psychiatry, I will establish whether changes in diagnostic practices and classification in psychiatry are warranted.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: MENTAL HEALTH
Title: Do no harm: A neural and ethical analysis of actions and omissions in moral decision-making.
Funder: Wellcome Trust

Abstract: I will utilize a combination of experimental tools to investigate the neural mechanisms driving systematic decision patterns related to the heuristic to do no harm. I initially develop a laboratory model of moral decision-making, demonstrating a greater aversion to harmful actions relative to harmful omissions in decisions involving real harmful consequences to an anonymous other person. Next, healthy participants will perform the task in an fMRI scanner, where I will use the model to test compe ting hypotheses that asymmetries in harm aversion for actions vs. omissions result from either (i) impoverished neural representations of the consequences of omissions, or (ii) stronger negative representations of harmful actions. I will then investigate whether asymmetries between harmful actions and omissions can be modulated by the neurotransmitter serotonin using a commonly prescribed antidepressant drug. Finally, I will explore the ethical and policy implications of my research findings. Du ring this time, I plan to apply for the Wellcome Trust-POST Fellowship where I can engage with a parliamentary audience on intervention strategies for relevant public health issues. My research will culminate in a number of research papers and a final dissertation describing the empirical findings and their implications for policy and practice.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: MENTAL HEALTH
Title: Risk of oesophageal cancer in patients previously hospitalised with eating disorder: retrospective cohort study in Scotland
Funder: Chief Scientist Office (Scotland)

Abstract: Oesophageal cancer is the eighth most common cancer, both in Scotland and worldwide. The sub-type, oesophageal adenocarcinoma, has been one of the most rapidly increasing cancers in Scotland in recent years. It has been suggested that the risk of oesophageal cancer, particularly adenocarcinoma, might be increased in patients with a history of eating disorders due to acidic damage to oesophageal epithelium caused by self-induced vomiting practiced as a method of weight control. Using linked records of hospitalisation, cancer registration and mortality in Scotland spanning 1981–2012, the purpose of this proposed study is to investigate the risk of oesophageal cancer among patients with a prior history of hospitalisation for eating disorder.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH;CANCER AND NEOPLASMS
Title: Cochrane Fellowship 2012- Eilis McCaughan- Online Support Groups for Women With Breast Cancer
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Breast cancer is the most common cancer in women, with an estimated 1.3 million new cases in the world in 2008 (Cancer Research UK, 2012). With advances in medical diagnostics and treatment, the number of cancer survivors, in the western countries at least, has increased dramatically. In the United Kingdom, there were 1.6 million cancer survivors in 2010 and it is expected that this figure will grow at over 3% a year (DoH, 2010). Breast cancer survivors are the largest group of cancer survivors (National Cancer Institute, 2010). While survival rates have improved, women with breast cancer continue to experience many physical and psychosocial problems following diagnosis, during and after treatment. Some of these issues include anxiety, depression, fatigue, effects on body image, loss of employment, side effects of treatment and breakdown in family relationships (DoH, 2010). Developing new models of care and support to meet the on-going needs of this growing population is a key priority for service providers. Support groups are a popular resource for people with cancer. In 2005 it was estimated that there were more than 400,000 internet cancer support groups (Im et al, 2005). The internet will increasingly be the arena of choice where psychosocial interventions will be delivered in the future, not least because it can be accessed with relative ease, from their own homes, by millions of people across wide geographical areas. The number of studies of online support groups for women with breast cancer has increased since Klemm et al (2003) identified six RCTs, in their review of online cancer support groups. To date, no systematic review of online support groups for women with breast cancer could be found. It is therefore timely to carry out a systematic review of the evidence on the effectiveness of these groups to inform users, practitioners, policymakers and researchers.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;7.3 MANAGEMENT AND DECISION MAKING
Health categories: MENTAL HEALTH;CANCER AND NEOPLASMS