NIHRDataInsights/HRCSData huggingface dataset:
Title: RAND Mental health Ecosystems Project
Funder: MQ: Transforming Mental Health

Abstract: Background The field of mental health research is large and complex. It covers a diversity of health conditions, employs a broad array of different research approaches, and is driven by a large and varied population of researchers and funding organisations. In a context where important, complex questions remain unaddressed and resources are limited, these characteristics present a significant challenge for efficiently and effectively coordinating and conducting research. Goals This study aims to support the coordination of mental health research by mapping the research funding ‘ecosystem’. It explores who the major funders are, what kinds of research they support, and how their strategies relate to one another. Specifically, it aims to: Identify the major funders of mental health research and map how they relate to one another; Review key funders’ strategies, identifying areas of duplication and difference; and Identify interesting and emerging practices in research funding. These aims are considered both at the global level and at the national level, focusing specifically on Canada and the UK. Methodology Phase I of the study uses a bibliometric analysis of funding acknowledgements on research publications to compile a global list of research funders. To ensure that this list is comprehensive and valid, a survey of researchers will be carried out to (i) confirm the organisations from which they have received funding and (ii) understand better how they consider the different kinds of funding they receive. The funders acknowledged most often will then be interviewed to explore in more depth their strategies, the ways they allocate funding and any collaborations they have with other funders. Once we have an understanding of the current funding landscape, Phase II of the study will focus on the future. We will carry out deep-dive reviews on a subset of key funders, exploring their strategies for the coming years and highlighting interesting and emerging practices.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: MENTAL HEALTH
Title: Integrating Behavioural Activation and Physical Activity promotion (BAcPAc): A pilot randomised controlled trial with depressed patients
Funder: Medical Research Council

Abstract: Phase I objectives will be as follows: (a) Involve service users and experts in physical activity (PA) promotion to identify how best to enhance a routine, evidence-based behavioural activation (BA) treatment for people with depression by adding a focus on PA behaviour change techniques in a novel intervention (BAcPAc) within the Improving Access to Psychological Therapies (IAPT) programme; (b) Develop a training programme for the Psychological Wellbeing Practitioner workforce to support the BAcPAc intervention; (c) Identify service level factors that may impact upon the implementation of the BAcPAc as part of the IAPT programme; (d) Identify appropriate process measures sensitive enough to differentiate between BA alone and BAcPAc. Phase II objectives will be as follows: (a) Undertake a pilot RCT of BA alone v. BAcPAc to confirm feasibility and clarify uncertainties in the design and delivery of a Phase III RCT; (b) Assess acceptability of the BAcPAc intervention among patients with depression. The RCT will involve 80 patients with moderate to moderately severe depression, recruited through primary care in Devon. They will be randomised to receive either routine BA therapy or BAcPAc in the form of weekly sessions for up to 12 weeks. Measures of PA, symptoms of depression, self-reported sleep, health related quality of life, health and social care service use, blood pressure and body mass index will be taken at baseline, 4, and 12 months from both arms The results will: (a) inform the design of an appropriately powered Phase III RCT to examine the effectiveness and cost effectiveness of the BAcPAc intervention for increasing and maintaining PA in patients recovering from depression; (b) inform the development of a training programme to enable the PWP workforce to support PA promotion as part of the BA protocol; (c) contribute to current debates about enahncing competencies associated with the PWP workforce to promote physical health.


Research activity codes: 6.7 PHYSICAL
Health categories: MENTAL HEALTH
Title: Investigating the neural basis for checking, selective attention and working memory in obsessive compulsive disorder, through MEG and TMS
Funder: Medical Research Council

Abstract: Compulsive checking, the most common symptom in OCD [6, 7] and present in about 15% of the typical population [7], will be targeted in a symptom-specific approach to candidate risk markers and endophenotypes of OCD that avoids inconsistencies due to phenotype heterogeneity [12]. By means of novel experimental paradigms, Magnetoencephalography (MEG) and frequency-tuned transcranial magnetic stimulation (TMS) we will provide unprecedented insights into the cortical networks involved in working memory and executive control and their dynamic interplay in compulsive checking as measured by means of phase- and amplitude relations within and across brain areas and frequencies. Substantial research by others and by our team suggests that neural oscillations are the key for understanding processing within- and between brain areas: A change in amplitude or phase of a single oscillation reflects a change in local neural processing, while amplitude and/or phase correlations (e.g. synchronisation) between two distant oscillations reflect the functional connectivity between two neural populations. Therefore, time-frequency components observed at the MEG sensors will be localized with Dynamic Imaging of Coherent Sources (DICS), developed by J Gross. DICS localises coherent sources in relation to a reference area, thus, identifying task-specific phase coupling between distant cortical areas. Significant oscillatory effects will then be correlated to behaviour and checking score, and will be targeted with frequency-tuned TMS, which is an emerging new technique developed by G Thut that mimics brain oscillations by means of short trains of magnetic pulses. This allows us to test the relevance of an oscillatory signature for overt behaviour in an unprecedented way. The main aim of the project will be to identify biomarkers for executive deficits in patients and people at risk and to provide a proof-of-concept for a therapeutic application of frequency-tuned Tms


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Investigation of the genetic causes of Specific Language Impairment (SLI) in an isolated Chilean population
Funder: Medical Research Council

Abstract: Specific Language Impairment (SLI) is diagnosed in children who experience profound and persistent language deficits despite otherwise normal development and no obvious explanatory factors. This disorder affects 5-8% of preschool children and has a complex genetic aetiology. Nonetheless, it is relatively under-studied and, to date, only three possible contributory loci have been identified. Over the last two years, we have been working with researchers from the University of Chile to investigate an isolated population in whom 35% of the children meet criteria for SLI. We have completed genome-wide linkage analyses in this population and identified significant linkage to chromosomes 6, 7, 12, 13 and 17 (maximum NPL score=7.56, P=3.2x10-14). In this application, we propose to extend these analyses by completing a comprehensive screen for common variations and rare mutations that may contribute to the high rate of SLI in this population. We will perform focussed association analyses of the identified linkage loci alongside genome-wide copy number variation and loss of heterozygosity investigations. Concurrent exome-sequencing of probands will enable the identification of rare coding mutations. All putative contributory variants (rare and common) will subsequently be investigated in British language-impaired families (SLI Consortium). This investigation has the power to identify numerous specific genetic variants that contribute to SLI susceptibility which will allow the formation of functional hypotheses.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Testing a Neuropsychological Model of Depersonalization with TMS
Funder: Medical Research Council

Abstract: Depersonalization disorder (DPD) comprises distressing and pervasive feelings of unreality and emotional numbing. Recent psychophysiological and neuroimaging research suggests dysfunction in the normal regulation of emotion - through reciprocal connections between right ventro-lateral prefrontal and limbic (including the insula) systems We will test the hypothesis that DPD stems from increased prefrontal-insula inhibitory regulation and predict that reducing frontal inhibition in patients with DPD should alleviate symptoms DPD is characterized by attenuated skin conductance responses (SCR), functionally related to reduced activation in brain areas underpinning affect, and by increased activation in prefrontal areas involved in emotion regulation. We will use MRI guided repetitive transcranial magnetic stimulation (rTMS) in contrasting, randomised, participant-blind interventions (low and high frequency stimulation and sham) in 3 groups of 20 healthy volunteers; and low frequency (versus sham) rTMS in 2 groups of 20 DPD patients; low-frequency TMS disrupts and high-frequency, enhances neural activity. We will measure two co-primary outcomes: objective SCR and subjective arousal ratings to emotional pictures. Symptoms of DPD will be a secondary outcome. We predict that: in DPD patients, low-frequency (1Hz) rTMS induced suppression of right ventro-lateral prefrontal activity will result in: increased SCR and enhanced subjective ratings of emotion to arousing pictures (plus reduced symptoms) versus pre-TMS levels; in healthy volunteers, high-frequency (10Hz) rTMS stimulation will activate the same prefrontal regions leading to transient blunting of subjective and autonomic responses resembling those of depersonalized participants, versus pre-TMS level. Low frequency will lead to increased emotion ratings, and sham no effects. The study will contribute to knowledge of emotional regulation and if positive, will pave the way for a therapeutic trial of rTMS in DPD.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Modelling psychosis using DISC1 human induced pluripotent stem cells
Funder: Medical Research Council

Abstract: Schizophrenia and major mental illness are devastating conditions with a combined lifetime prevalence of over 10%. Whilst partially effective treatments are available, none are clearly disease modifying. Notwithstanding important insights provided by animal models there is a great and unmet need for further models of mental illness in order to develop more effective therapies. The t(1;11) translocation1, discovered in a large multiply affected Scottish family in very close contact with the Division of Psychiatry, is one of the strongest single genetic risk factors identified for major psychiatric disorders. Combining genetic discoveries with advances in reprogramming and resulting derivation of human induced pluripotent stem cell lines (hIPS) now allows human based disease models and several studies have demonstrated the feasibility of this approach for both neurological and psychiatric disorders. The current proposal brings together major strengths in clinical psychiatry - specifically our ongoing and long-term study of the t(1;11) family, neurophysiology, molecular genetics, stem cell biology and in vitro disease modelling. We propose to develop a human in vitro model of psychosis by obtaining and then validating induced pluripotent stem cells, neural progenitors and forebrain neurons from individuals with and without the t(1;11) translocation. We will then conduct a number of comparative studies examining the effects of the translocation on neuronal structure and function, dendritic arborisation and spine density, before examining the effects on DISC1/DISC2 and NMDAR expression.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Identification of Major Risk Alleles for Schizophrenia in Consanguineous Families
Funder: Medical Research Council

Abstract: Schizophrenia is a common yet poorly understood chronic mental illness. Ranked by the WHO as equivalent to heart disease and cancer together in disability terms, it often persists throughout adult life, resulting in a substantial burden on families and cost to society. Currently available treatments treat only positive (hallucinations, delusions, thought disorder) and not negative (decreased motivation, emotional blunting) symptoms or cognitive deficits, are ineffective in up to 30% of patients and have unacceptable side-effects. There is therefore a clear need for new and better therapies, for which a better understanding of the aetiological basis is an essential prerequisite. Family studies suggest a significant genetic contribution. Identifying the genes involved will offer valuable insights into the pathways affected, and will help dissect environmental contributions. However, the GWAS approach used by most psychiatric geneticists to date has delivered only limited successes and there remains much controversy around our genetic understanding of schizophrenia. We propose instead to use autozygosity mapping in multiplex Pakistani families. The Pakistani community of West Yorkshire is both highly consanguineous, increasing the frequency of all recessive disease, and endogamous, potentially reducing genetic complexity. This approach presumes that, in at least some families, the disease is caused by a single recessive mutation with high penetrance. Others have suggested this approach will not work because schizophrenia is too complex. However, our initial findings show that in one family this approach has worked spectacularly well, proving the existence of a locus on chromosome 13q and revealing the first documented case of "Mendelian" schizophrenia. We now seek funding to identify the gene and mutation on 13q, then to repeat the process in further consanguineous Pakistani families to locate and identify more genes mutated in schizophrenia.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH
Title: Psilocybin as a treatment for major depression
Funder: Medical Research Council

Abstract: This will be a double-blind, randomised, placebo-controlled, between subjects study involving up to 44 patients (22 per group) with major depression of moderate to severe degree (scores of 14+ on the Hamilton Depression Rating scale). The main objective is to test the efficacy of psilocybin infusion as a treatment for major depression. All patients will be at least 21 years of age with decent physical health and at least one failed treatment with an antidepressant medication within the last 4 months. All patients will be medication free for at least 7 days prior to screening. Patients will be recruited via referrals and advertisement. The study will be adopted on to the Medical Health Research Network. Patients will be screened for suitability. Exclusion criteria will include: epilepsy, cardiovascular abnormalities, history of drug or alcohol dependence, history of psychosis, psychotic symptoms, bipolar disorder, or high schizotypy, and a history of suicide attempts or planning. The study duration from screening to the final formal follow-up will be 4 weeks. Upon enrolment, patients will be randomly allocated to 1 of 2 treatment groups: placebo (2 IV infusions of saline, 7 days apart) or psilocybin (2 IV infusions of psilocybin - a low dose (0.9mg) and then a high dose (1.8mg), 7 days apart). After screening, there will be a run in period of 7 days, followed by the first treatment session at day 7, a second treatment session at day 14 and a final follow-up at day 28 after which the study will end. The primary outcome will be change in BDI scores from baseline to week 4. We predict that patients in the psilocybin group will have significantly greater decreases in BDI scores than patients in the placebo group. Psilocybin will be given by IV infusion. Given IV, the acute subjective effects of psilocybin are short-lived and well-tolerated, lasting for approximately 40 minutes.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Towards a translational experimental model of anxiety for pharmacological and psychological treatment development.
Funder: Medical Research Council

Abstract: There is considerable need to improve outcomes in patients with anxiety through developing valid experimental human models of anxiety that improve on the poor predictability of preclinical animal models and allow us to more effectively evaluate novel pharmacological and psychological treatments (and mechanisms of action) in healthy volunteers, prior to phase II/III clinical trials in patients. Inhalation of 7.5% carbon dioxide increases anxiety, autonomic arousal and induces neuropsychological deficits and biases in emotion processing in healthy individuals, and provides a putative translational experimental model of generalized anxiety disorder. Using a new extended version of the CO2-model we will evaluate the effects of promising drug treatments with varied mechanisms of action (e.g. serotonin, noradrenaline, glutamate & melatonin) across CO2-induced subjective, autonomic and neuropsychological outcomes. Third-wave cognitive behavioural psychological treatments may alleviate anxiety symptoms but future development will require clarification and experimental comparison of core component processes that may differentially mediate clinical improvement. Using the CO2 model we will evaluate 'attention control' and 'acceptance' modules emphasized in third-wave CBT interventions. We will also examine the effect of a computerized 'attentional bias modification' training protocol on subjective, autonomic and neuropsychological response to CO2 challenge, consistent with a need to evaluate its generality over time, stressful situation and across multiple outcome measures. We will translate the CO2 model into the clinic to examine whether subjective, autonomic and neuropsychological response profiles to CO2 in GAD pretreatment i) covary with illness severity, and comorbidity, ii) distinguish/differ across GAD, unipolar depression and comorbid GAD/depression, iii) predict subsequent response to treatment, and iv) resolve (at follow-up) with pharmacological treatment.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;5.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Attentional Bias Modification: Development and testing of a school-based "Cognitive Vaccine" for the reduction and prevention of child anxiety
Funder: Medical Research Council

Abstract: Childhood anxiety disorders are highly prevalent and place a significant health and wealth burden on the individual and wider society. Targeting at-risk children through prevention programs, especially during periods of high stress could be an effective means of intervening to reduce this burden. Attentional biases to threat represent a causal vulnerability factor for experiencing anxiety. Interventions that target attentional biases should act as a cognitive vaccine, increasing immunity against experiencing anxiety to stress. The current proposal considers whether a cognitive manipulation, which modifies dysfunctional attentional biases in children at elevated risk for feeling anxious, represents an effective vaccine against experiencing anxiety.The proposed research will assess the efficacy of a novel computerised intervention designed to alter attentional bias, the attentional bias modification task (ABM). Study 1 will establish which type of stimuli it is most useful to train children's attention to. Study 2 will establish the best time-line by which to deliver the protocol. Study 3 tests whether ABM can act as a vaccine, enabling children to cope better in response to a lab-based and a naturalistic stressor. The efficacy of the manipulation will be assessed using established measures of attentional bias and self-report, observational and physiological measures of susceptibility to experiencing anxiety in response to lab-based and naturalistic stress. All experiments will employ a randomised mixed design with participants being allocated to active ABM or a control group. Outcome measures will be assessed at multiple time points. This project will provide proof of concept data on the use of ABM as a preventative intervention before deploying it in larger scale clinical trials. Findings would have implications for our understanding of the cognitive processes underpinning child anxiety and for reducing health and wealth burdens through its prevention and treatment.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Facing up to Faces: Changing biases in face perception to improve emotional processing in mental health
Funder: Medical Research Council

Abstract: Mood disorders are highly prevalent in the general population, dominated by major depression, and constitute a substantial burden of disease - in Europe 7.2% can be attributed to depression. There is therefore a pressing need for interventions to address this. Here we propose a study to investigate the potential of a novel cognitive bias modification technique for reducing negative mood and improving positive mood in an analogue population of those with high levels of depressive symptoms This targets biases in emotional processing characteristic of depression. We have developed a new paradigm which targets the recognition of emotions by assessing the threshold for detecting emotion in an ambiguous expression (e.g., a blend of happiness and sadness), and then providing feedback to modify this (e.g., to favour identification of happiness). Preliminary results show that this manipulation, designed to promote the perception of positive emotion over negative emotion, results in improved positive mood at two-week follow-up. We propose two workstreams to develop these initial findings. The first will establish the effects of this training on a larger sample of individuals with high levels of depressive symptoms over six-week follow-up. The second will identify the neural substrates targeted by this procedure. This research will allow us make the critical next step in the development of this intervention, moving from proof of concept to clinical translation. It has the potential to inform the development of a novel treatment for depression which could be used alongside existing treatments. In principle this could be delivered automatically via computer, internet or smartphone. It therefore has exciting potential to be a valuable cost-effective adjunctive treatment for depression. In addition, the technique can be adapted for use in other psychopathologies where emotion recognition biases or deficits have been implicated, such as schizophrenia, autism and addiction.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH