NIHRDataInsights/HRCSData huggingface dataset:
Title: Conduct Problems in children: Refining the neurocognitive phenotype
Funder: Medical Research Council

Abstract: The proposed research aims to delineate psychological and neural processes that are compromised in children with conduct problems Specifically, we will compare children with conduct problems and high callous-unemotional traits (N=35), children with conduct problems and low callous-unemotional traits (N=35), and ability/SES/sex matched typically developing control children (N=35) on a range of behavioural and neuroimaging tasks. We will assess how these children process their own emotions, how own emotion processing relates to processing of other people's emotions / empathy, and whether attention / familiarity can modulate emotion / empathy processing in the two subgroups with conduct problems Data Analysis: i. Behavioural data: Analyses will be conducted using SPSS software with in-house statistical consultation where appropriate. Standard parametric analyses (e.g. ANOVA) will be used to analyse the behavioural data. Mean scores, measures of standard error and effect sizes will be calculated and a predefined procedure for removal of outliers will be implemented for any reaction time data. ii. fMRI data: Functional MRI images will be analyzed using Statistical parametric mapping as implemented in SPM8 software. After realignment, normalization and smoothing of the images, each experimental condition will be modelled separately using a synthetic hemodynamic response (HRF) function. For each fMRI task the General Linear Model (GLM) will be used to compare experimental conditions by group (CP/high CU traits, CP/low CU traits and TD) using GLM Flex (http://nmr.mgh.harvard.edu/harvardagingbrain/People/AaronSchultz/GLM_Flex.html). Further analyses will explore whether brain activity to own emotions correlates with brain activity to other people's emotions / empathy across tasks. The role of attention / familiarity in modulating emotional / empathic response to others will also be investigated.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: MICA: SRC inhibitors as potential antipsychotics: human testing with psilocybin
Funder: Medical Research Council

Abstract: This double-blind, randomised, placebo-controlled, study will involve 24 healthy volunteers. The main objective is to test the ability of the Src-kinase second messenger inhibitor AZD0530 (saracatanib) to attenuate the neuroimaging and subjective markers responsive to psilocybin infusion. Psilocybin is found in some species of mushroom. It is structurally similar to the brain neurotransmitter serotonin - which is implicated in mood and schizophrenia. Volunteer screening will comprise medical history, physical examination, psychiatric interview, safety blood screening and urine dipstick tests for drugs of abuse, pregnancy test (females) and electrocardiogram. Volunteers will be excluded if they suffer from cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or psychiatric or neurological disorders capable of significantly affecting the safety or validity of the study. Failed drugs of abuse screening, weekly alcohol intake over recommended levels or caffeine intake equivalent of >6 cups of coffee per day or failure to pass the MRI screening will also constitute exclusion. Subjects will have had prior psilocybin experience. The duration of the study participation will be approximately 4 weeks, with at least 1 week between study visits to allow adequate wash out of the oral drug. Each participant will receive: placebo + psilocybin infusion (2mg in 10mL saline) or 50mg saracatanib + psilocybin or 175mg saracatanib + psilocybin. Four hours after oral drug administration scanning will comprise: resting state fMRI, a visual coherence task, perfusion imaging (during which psilocybin will be infused) followed by a repeat of the resting state and visual coherence task. The primary outcome will be reduction in perfusion signal in the anterior cingulate cortex and the attenuation of this in a dose dependent manner by saracatanib.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Personalised monitoring and enhanced self-management in mental health (CareLoop)
Funder: Medical Research Council

Abstract: Serious mental health problems such as schizophrenia affect 2% of people. Typically the onset is in early adult life, followed by lifelong vulnerability to relapse resulting in unscheduled inpatient admission. Care is usually delivered via secondary mental health services which aim to provide community-based support. A person's symptoms, mood and functioning will fluctuate in response to a variety of factors. This can lead to adverse outcomes including relapse, self-harm, and need for unscheduled acute care. Currently, symptom monitoring relies on clinical interview at infrequent intervals, with limited ability to detect sudden change. Supported by MRC DPFS funding (G0901434), we have developed a personalised technology (ClinTouch) that enables a person's symptom data to be captured several times daily and uploaded wirelessly to a database to create a high-resolution record of symptoms and their fluctuations. We have shown that 85% of people with psychotic problems are able to use the technology appropriately over a week and that the data collected correlate well with the gold-standard clinical interview rating scales. This has the potential to enable targeted intervention and help users better to manage their own condition and received care. The current proposal, CareLoop, is to build an end-to-end system using widely available technologies based on open standards for long-term symptom monitoring, guided by qualitative input from patient and professional users, that can be personalised and linked to clinical management algorithms We will undertake a proof of concept feasibility trial in 2 clinical sites, where it will be used by patients and carers over periods of 3 months. The results will inform a future phase 3 effectiveness trial and the shape of collaborations with commercial partners. The system has the potential to transform community care for people with serious mental illness, and can enhance the quality of clinical and personal illness management


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH
Title: Cannabidiol: a novel treatment for cannabis dependence?
Funder: Medical Research Council

Abstract: Background: In Europe 1% of all adults and nearly 2% of 14-17 year olds are addicted to cannabis and 28% of all new drug treatment admissions are now for primary cannabis dependence. There is no medication for cannabis dependence. An effective treatment would impact significantly on medical and legal costs, on young people's educational achievement and their risk of mental health problems Proposed solution: Based on a strong preclinical rationale, our own extensive human data and the importance of the endocannabinoid system in reward and addiction, cannabidiol (CBD) is a highly promising treatment which has excellent tolerability and safety. Objectives: To determine the optimal dose of CBD and its efficacy in the treatment of cannabis dependence. Design: Stage 1 (dose-finding study) will randomly allocate 16-26 year olds who meet DSM criteria for cannabis dependence to parallel groups administered oral CBD 200, 400, 800mg or matched placebo for 28 days. Independent data review at specified recruitment points will identify doses of interest based on significant reductions in urinary THC-COOH, self-reported cannabis use and withdrawal intensity. If Stage 1 successfuly identifies a Most Effective Dose (MEDmg) of CBD, Stage 2 will expand existing group numbers by allocating new participants to MEDmg or placebo (total N=120). Primary success criteria include: more abstinent cannabis users (ideal criterion), more non-dependent users (acceptable criterion) and reduced withdrawal intensity in the CBD than placebo group. Secondary criteria include improved memory, psychological well-being and days in work/education. Application/exploitation: The findings would have broad application given the world wide prevalence of dependent cannabis use and associated medical, psychological and social consequences. The success of this study would provide a very strong impetus for a large scale clinical trial.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Translating gene-environment interaction from aetiology to personalised medicine for anxiety and depression.
Funder: Medical Research Council

Abstract: Aim: To investigate whether genes that moderate the effects of the environment on the development of depression and anxiety may also predict response to psychological treatment. Objectives 1. Examine the extent to which genes moderate the effects of the environment on anxiety and depression. 2. Identify the genetic variants involved. 3. Test these variants as predictors of response to CBT. Methods Objective 1 Sample: 10,301 twin and sibling pairs. Analyses: An established quantitative-genetic model to test for gene-environment interaction will be used to examine the extent to which genes moderate the effects of positive and negative environments on depression and anxiety. Objective 2 Sample: 1,183 monozygotic twin pairs. Analyses: A novel extension of the monozygotic twin differences design, which examines within-pair discordance as a function of genotype, will be used to identify genetic variants that moderate the effects of the environment on depression and anxiety. Objective 3 Sample: 2,000 anxious children treated with CBT and 400 depressed adults treated with either CBT or medication. Analyses: Genotypes detected in Objective 2 will be tested as predictors of change and remission of symptoms Scientific and medical opportunities: The results of this research may have far reaching implications for understanding the aetiology of depression and anxiety and their prevention and treatment. Variants suggestive of increased environmental sensitivity may enable targeted interventions for individuals at a high-risk of developing these disorders. These same genotypes may also be used to select the most effective treatment for a given patient. Given their prevalence, and their substantial social and economic costs, advancing the prevention and treatment of depression and anxiety would lead to improved mental health and well-being for a significant proportion of the population and ultimately benefit society as a whole.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: LONG TERM OUTCOMES AND HEALTH INEQUALITIES IN BIPOLAR AFFECTIVE DISORDER WITHIN A UK PRIMARY CARE COHORT (1995-2012)
Funder: Medical Research Council

Abstract: Aims To examine i) long-term serious adverse outcomes in bipolar disorder (BPAD), and ii) whether socio-demographic gradients exist in access to treatment and clinical outcome Objectives 1. To determine the long term prognosis of patients with BPAD, by identifying rates of serious adverse outcomes: i) hospitalisation and crisis team intervention, ii) self-harm, iii) suicide and iv) all cause mortality 2. To determine if proportion of time in treatment, and treatment type, predict rates of serious adverse outcome 3. To determine whether social gradients exist in: i)The receipt of appropriate psychotropic medication, ii) The rate of serious adverse outcomes 4. To describe time trends in any such associations, in relation to changes to GP contract and financial incentives for care for Severe Mental Illness (the Quality and Outcomes Framework) Methodology THIN is one of the largest sources of primary care data in the UK, with information on over 20,000 patients with BPAD, it contains records of each patient's medical conditions, symptoms, and medications. The study will compare individuals with BPAD by time in treatment and treatment type. Outcomes will be serious adverse events. Social gradients in access to treatment and frequency of negative outcomes will be examined. Statistical techniques will be used to reduce confounding by indication and other biases related to unmeasured covariates. Scientific & medical opportunities An understanding of long term outcomes and existence of health inequalities in BPAD is lacking. Large-scale observational studies will be needed to fill this gap. The project will lead to identifying demographics of at risk groups, treatment that offers an improved quality of life for those with BPAD and a decreased negative impact on society. The argument for use of primary care data for outcomes/health inequalities research in other databases and areas of medicine will be strengthened.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: MENTAL HEALTH
Title: The effect of 0ethnic density on psychosis incidence
Funder: Medical Research Council

Abstract: STUDY AIM to investigate the effect of ethnic density on the risk of psychosis among black and minority ethnic (BME) groups STUDY OBJECTIVES to assess: 1) whether greater ethnic density, at neighbourhood area level, is inversely related to psychosis incidence for members of BME groups, after prior address history is accounted for 2) whether there are significant differences in this effect between ethnic groups, 3) whether this effect is different for sub-groups of psychotic illness (affective / non-affective) 4) whether this differs at different neighbourhood levels 5) how this might differ in different urban areas, both nationally and internationally 6) possible underlying mechanisms behind these effects reflecting, for example, aspects of social cohesion, social support and social alienation. METHODOLOGY I will use a mixed methods design: Study 1 - Initial analysis using detailed psychiatric linked to stratified area census records (covering 180,000 mental health service users in SE London, including detailed free text allowing address history to be tracked prior to illness onset) - meeting objectives 1 - 4. Study 2 - Using primary care records (covering 900,000 patients in 1 SE London and 3 East London boroughs) to extend the analysis (validating against the above linked psychiatric records) - obj. 1 - 5. Study 3 - Qualitative study of life history accounts of neighbourhood factors (comparing accounts in high and low ethnic density areas to generate hypotheses as to mechanisms behind ethnic density effect) - obj. 6 Study 4 - Further analysis of linked records (to investigate possible mechanisms behind the ethnic density effect informed by study 1-3) - obj. 6 Study 5 - International comparison study (apply analyses to similar data collected in Netherlands)- obj. 5. SCIENTIFIC AND MEDICAL OPPORTUNITIES This has the potential to illuminate mechanisms behind ethnic differences in psychosis that would inform treatment and prevention.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Exploring frailty, mental health and related outcomes: a multi-cultural population-based approach to ageing.
Funder: Medical Research Council

Abstract: There is considerable debate on the definition of frailty, a syndrome that is strongly associated with age and that is often associated with an increased risk of poor outcomes. There is very little evidence that the construct and predictive validity of the different definitions of frailty apply to low and middle-income countries, places where the demographic transition is occurring most rapidly. Other conditions that have often been neglected in the epidemiological literature of those settings are Common Mental Disorders (CMD), which criteria partially overlap with those of frailty. A main limitation in the frailty field is that early operationalisations have been mainly driven by clinical insights, with rather simplistic theoretical underpinnings, and no empirical support other than for predictive validity. Using data from a large international and multi-cultural population-based survey, the 10/66, I plan to investigate the construct and predictive validity of current definitions of frailty, particularly focusing on the contribution of CMD to frailty and to identify sub-phenotypes that are most closely aligned to cognitive and physical frailty. Replication cohorts that I am also planning to use to validate and compare the findings are the Longitudinal Aging Study Amsterdam (LASA) and the Lothian Birth Cohorts. The approach is integrative and comprehensive with respect to age-related changes in cognitive, physical and psychological domains. It also uses sophisticated statistical analytical procedures to explore the construct validity of frailty, and the relationship between specific domains of frailty and different policy relevant outcomes. Risk predictions models to aid clinicians and policy-makers will also be built at the end of the project. This project will provide strong evidence in understanding the impact of frailty and common mental disorders on ageing populations and to identify potential pathways and modifiable factors for intervention.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MENTAL HEALTH
Title: Enhancing speech fluency with non-invasive brain stimulation in Developmental Stuttering
Funder: Medical Research Council

Abstract: The main aim of this project is investigate the effects of Transcranial Direct Current Stimulation (tDCS) of motor speech brain regions to improve speech Developmental Stuttering (DS). The study objectives are to 1) Measure behavioural changes associated with single sessions of tDCS to speech motor brain regions paired with a speech task, in DS 2) Measure neurophysiological changes resulting from this intervention, in DS 3) Measure behavioural and neurophysiological effects of tDCS paired with fluency therapy over an extended period (5 consecutive days intervention). Methodology: tDCS: All studies will use anodal tDCS, which increases neuronal excitability, and improve task performance. The anodal electrode will be centred on electrode position FC5 in international EEG 10-20 positioning system in left hemisphere. The electrode area (5x7cm) will cover inferior frontal cortex. The reference electrode placed on the contralateral supraorbital ridge. 1 mA direct current will be applied for 20 minutes, whilst the participant completes a speech task. Magnetic Resonance Imaging: High resolution structural and and echo planar (functional) images of the whole head will be acquired using a 3 Tesla imaging system. A sparse sampling methodology will be used to reduce motion artefacts due to participants completing speech tasks. Concurrent tDCS with fMRI will be achieved using an MR compatible DC stimulator. Magnetoencephalography (MEG): A wholehead 306 channel magnetometer will be used to record neuromagnetic responses in motor speech regions, whilst participants complete speech tasks.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Does the metabolic syndrome impair recovery from traumatic brain injury: a prospective neuroimaging and cognitive study?
Funder: Medical Research Council

Abstract: Background: Traumatic brain injury (TBI) is a common cause of disability but there are no current treatments that aid brain repair. Objective: To investigate whether the frequently occurring metabolic syndrome impairs recovery from TBI. Aims: To see if the presence of metabolic syndrome or insulin resistance in patients after TBI: 1) impairs brain repair, demonstrated by magnetic resonance imaging (MRI) measures of traumatic axonal injury. 2) impairs recovery of cognitive function, measured by information processing speed and attention, and other clinical symptoms 3) is associated with higher levels of persistent neuroinflammation measured using TSPO-R positron emission tomography (PET). Methods: Prospective study comparing patients with and without the metabolic syndrome following moderate-severe TBI. Patients will be studied both at baseline and after one year follow-up with: (i) full clinical assessment in an established multidisciplinary TBI clinic including metabolic and endocrine phenotyping with measurements of dyslipidaemia, impaired glucose homeostasis, insulin resistance and hypertension; (ii) detailed structural MRI scans including T1,T2, SWI and diffusion tensor imaging (to analyse white matter tract structural integrity); (iii) functional MRI scans to assess network integrity; (iv) cognitive measures of processing speed and attention, and symptomatic, psychological and quality of life assessment through validated questionnaires; (v) brain PET scanning with the ligand [18F]GE-180 (at baseline only) to measure microglial activation to establish if brain inflammation is an underlying explanatory mechanism. Opportunities: The demonstration that metabolic syndrome impairs recovery after TBI will encourage investigation of the underlying mechanism through pre-clinical studies and eventually trials using currently available drugs for metabolic syndrome to improve clinical outcome in TBI.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: E Kinyanda, MRC/UVRI Uganda Research Unit on AIDS - Mental health among HIV infected CHildren and Adolescents in KAmpala, Uganda (CHAKA)
Funder: Medical Research Council

Abstract: Prevalence/incidence of the broad categories of emotional and behavioural disorders, sub-diagnostic categories (including neurocognitive impairment) will be estimated with 95% confidence limits, overall and by site location, age-group and gender. A hierarchical approach will be used to investigate factors associated with PD. The impact of PD on HIV disease progression on CA-HIV on antiretroviral treatment (ART) will be assessed using a linear mixed model fitted to the longitudinal data consisting of transformed CD4 counts at baseline and six and 12 months, with fixed terms for the presence/absence of PD, gender, age (as a continuous variable) and other prognostic factors, and a random effect for subject. For those not on ART, a binary variable will record whether or not the viral load is greater than 1,000 copies/ml. A similar analysis will then be carried out, except a generalised linear mixed model (GLMM) will be fitted. The relationship between polymorphisms of the serotonin transporter gene and depressive disorder will be evaluated using mixed-effects logistic regression. We will use a stepwise selection procedure using the Akaike information criteria to select the specific combination of interactions and main effects out of the candidate model containing all individually significant factors. To assess the impact of PD on social and academic functioning and risky behaviours, these outcome measures will be transformed into binary variables (e.g. the dichotomised "poor academic functioning") and then GLMMs will be fitted to the longitudinal data at each time point (i.e. baseline and six and 12-month follow-up). Forty-eight CA-HIV diagnosed with a psychiatric disorder (PD) and their caregivers will be asked to participate in the qualitative sub-study. Thematic analysis will be conducted to elicit common experiences that emerged from the participants' narratives. In addition simple frequencies will be tallied for the various symptoms described.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH