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SSC Psychiatry Research with Neuroscience Module 1 September – December 2013 Project Title & Summary 1. Trauma and forensic populations Much has been written about the impact on adult mental health of trauma, whether that is childhood trauma, adult trauma, or for example combat-related trauma. There is a growing body of literature on the impact of combat-related trauma on violent and aggressive behaviour but less has been written about the link between trauma-related mental health problems in the general population and violence. Past trauma is an underexplored risk factor for subsequent violence and a better understanding of the pathways to violence following traumatic experiences could improve management of many patients within forensic services or could help prevent individuals ending up in forensic services. Supervisor(s) Dr Deirdre MacManus Research Fellow Specialist Registrar Forensic Psychiatry [email protected] I propose a literature review of research which has studied the impact of a variety of life-time traumatic experiences on violent behaviour to lead onto a discussion of how our knowledge in this area may aid our management of aggressive and violent behaviour among patients with trauma-related disorders, especially those who find themselves under the care of forensic services. 2. What is the effect of gentrification in a neighbourhood on mental health Dr Laura Goodwin Lecturer in Epidemiology outcomes? King’s Centre for Military It is well established that where an individual lives and the neighbourhood Health Research characteristics impact on a range of health outcomes, health behaviours and mental Department of Psychological health. Change in a neighbourhood can occur either through the process of Medicine gentrification which can broadly be defined as higher-income households moving into lower-income neighbourhoods, or through government led regeneration [email protected] projects, and negative change may occur when a neighbourhood becomes more deprived and those who can afford to will move away. Whilst the gentrification phenomena could be viewed as improving the facilities available to all individuals Dr Charlotte Woodhead in a neighbourhood, it may also result in social segregation between middle and Researcher lower SEC groups and potentially to socio-spatial segregation when lower SEC Psychological Medicine groups are displaced and priced out of their neighbourhood. By using existing longitudinal studies, epidemiologists and health [email protected] researchers have been able to study the effects of change in various neighbourhood k characteristics and composition on various health outcomes, on those who remain in the same area, including change in health over time. The objectives of this literature review are to focus on mental health outcomes and to review studies which have looked at the effects of change in neighbourhood on mental health. Boyle P., Norman P., Rees P. (2004). Changing places. Do changes in the relative deprivation of areas influence limiting long-term illness and mortality among non-migrant people living in non-deprived households?. Social Science and Medicine. 58 (12), 2459-2471. Butler, T. & Robson, R. (2001). Social Capital, Gentrification and Neighbourhood Change in London: A Comparison of Three South London Neighbourhoods. Urban Studies, 38, (12), 2145–2162 Dalgard O.S., Tambs K. (1997). Urban environment and mental health. A longitudinal study. British Journal of Psychiatry. 171, 530-536. 3. Oxidative stress and depression Many neurodegenerative and neuropsychiatric diseases, including depression, have recently been linked to oxidative stress, a pathological condition arising when physiological oxidative actions by reactive oxygen species are no longer balanced by antioxidative defenses. At the same time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in the same conditions. Glutamate and related acidic amino acids are the major excitatory neurotransmitters in the brain and may be utilized by 40 percent of the synapses. Thus, two broad mechanisms -oxidative stress and excessive activation of glutamate receptors- are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain. We want to review the molecular pathways underlying these mechanisms. Dr Patricia Zunszain Researcher Psychological Medicine [email protected] 4. Systematic review of the evidence for linking personality factors to physical health disorders Dr Piyal Sen Consultant Forensic Psychiatrist It is only in the field of Cardiology that we see personality being mentioned, with Visiting Research Fellow, Type A personality type being more likely to suffer from coronary heart disease as Institute of Psychiatry, opposed to Type B. However, there is a link between anxiety and a number of King's College, London physical health conditions like diabetes, cancer, infertility, Irritable Bowel and St. Andrew's Syndrome, etc, while the anxiety itself could well be a product of the type of personality. There is some evidence from the field of personality disorder that these Academic Centre, Northampton. patients attend doctors more frequently, but if a genuine link is found between personality factors and some types of physical disease, there is a strong case to carry 01268 723847 [email protected] out personality screening assessments in these clinics and offer basic psychological therapy to address those personality difficulties through liaison psychiatry or [email protected] through IAPT interventions. The research case to explore this is thus very strong. (please send any emails to both addresses) 5. Systematic review of the evidence of whether certain personality traits or disorders are more predictive of PTSD or depression after experiencing a traumatic event. Compensation claims continue to increase in all areas of British society, whether it be the effect of a road traffic accident or being badly treated by the police following stop and search, or being treated poorly while in hospital or prison. If it is established that certain personality traits or disorders are more predictive of an adverse reaction to a traumatic event, this will also help to answer prognostic calculations about the likelihood of a full recovery, which might assist towards the assessment of the level of compensation. This could also assist authorities who might be the victim of a compensation claim to be more cautious in their treatment of individuals judged to be more vulnerable than others because of their personality and devise some basic screening test for this in settings like police stations, prisons, hospitals, etc. Dr Piyal Sen Consultant Forensic Psychiatrist Visiting Research Fellow, Institute of Psychiatry, King's College, London and St. Andrew's Academic Centre, Northampton. 01268 723847 [email protected] [email protected] (please send any emails to both addresses) 6. Human stem cells as models of autism spectrum disorders Further details to be discussed with supervisor Prof Noel Buckley Professor of Molecular Neurobiology Centre for the Cellular Basis of Behaviour (CCBB) [email protected] 7. Reward sensitivity in schizophrenia: a systematic review A main limitation in current diagnostic criteria is the lack of correspondence between symptoms and pathophysiological mechanisms. Many advocate a shift to a classification system with a clear association with biological mechanisms. However, our current understanding of the neurobiology and genetics of psychiatric disorders is largely insufficient to advance alternative classification criteria. One of the major limitations in developing this framework is the lack of a clear correspondence between biological and behavioural abnormalities. Recently the National Institute of Mental Health in the US advanced an alternative framework to study mental health conditions called the Research Domain Criteria (RDoC). RDoC aims to be a biologically-valid framework for the understanding of mental disorders. Converging research indicates that individuals with schizophrenia show a marked impairment in tasks involving sensitivity to feed-back. Sensitivity to feed-back is a basic function needed to regulate our behaviour following positive and negative consequences which is essential for learning and decision-making. Deficits in reward sensitivity in particular have been associated with the dopamine system which is thought to be implicated in the pathophysiology of schizophrenia. Reward sensitivity has been put forward as one of the five RDoC as this mechanism is considered promising in linking the biology and the behaviour. The current project aims to systematically review the research conducted on reward learning in schizophrenia to highlight associations between behavioural adaptation (i.e. learning) and biological mechanisms. Knowledge in this area will inform both biological theories of dopamine imbalance but also psychological interventions for symptoms of schizophrenia resulting from reduced reward sensitivity (e.g. poor motivation, anhedonia). Clementine Edwards PhD Student Department of Psychology [email protected] k Dr Matteo Cella Lecturer Department of Psychology. [email protected] 8.Title TBC The 2009/10 pandemic saw the mass distribution of antiviral drugs to the general population, using a novel system involving the automated assessment of symptoms via an on-line service and the issuing of a unique authorisation code which could be taken to a pharmacist. This model was useful during the pandemic, and public health experts are now interested in its applicability to other situations where mass distribution of medicines may be needed. Dr James Rubin Senior Lecturer in the Psychology of Emerging Health Risks Psychological Medicine [email protected] Yet while the supply of medicine worked well in the pandemic, adherence by the public was remarkably low. Estimates suggest that fewer than 50% of the antivrals issued were actually taken. If we are to develop the mass distribution system further, understanding the behaviour of the patient once they receive their authorisation code is clearly essential - why do some not collect their tablets at all, while others cease taking their tablets before they have finished their course? In this review, we will identify all studies relating to the pandemic which provide data on this issue. We will provide a list of the key risk factors for non-adherence to antivirals and attempt to quantify these risk factors where possible. The review will then inform a larger body of work on this, currently being run by KCL, UCL and Public Health England. 9. Biological correlates of cognitive decline in Alzheimer’s disease Dr Wendy Noble Lecturer in Neuroscience Alzheimer’s disease (AD) brain is characterised by deposits of β-amyloid (Aβ) in King's College London neuritic plaques, intracellular neurofibrillary tangles (NFTs) comprising aggregated Institute of Psychiatry tau, synaptic dysfunction and neuronal loss. Accumulating evidence suggests that it Department of Neuroscience is not the presence of plaques and tangles themselves that cause damage to synapses (PO37) and loss of neuronal function, but rather that the damage is caused by specific alterations to the structure or localisation of tau and A that occur before their inclusion into filamentous lesions. Since progressive synaptic dysfunction and neuronal loss gives rise to the clinical symptoms of dementia and a spectrum of additional cognitive and behavioural abnormalities, it is important that we develop a more complete understanding of the biological events underlying synaptotoxicity and neurodegeneration in AD. To address this aim, the student will conduct a literature review of the pathological correlates of disrupted neuronal functioning and cognitive decline in AD. 10. Multi-dimensional description of the delivery of psychotherapy: a systematic review and a proposal Psychotherapy traditionally occurred once a week as an outpatient. Over the past couple of decades there has been an upsurge of interest in the delivery of psychological therapies in different formats and intensities. Thus a trial might investigate (a) the numbers of sessions (e.g “one session treatment”, “brief” therapy or long term therapy (b) the duration of sessions (c) the frequency of sessions (e.g. sessions delivered intensively over a week or every other day) (c) different levels of training and experience of a therapist (e.g. low intensity Psychological Well Being Practitioners v highly experienced therapist) (d) individual or group or family therapy (e) different settings (e.g home treatment; internet delivered therapy; outpatient; residential) (f) different formats (e.g. written text, video or computer software; face to face). Different researchers and therapists may use different terms to describe the same format or the same term to describe different formats. Thus the term “low intensity” is used by NICE to mean the number of sessions or the delivery of the therapy over the telephone or by the type of therapist. Dr David Veale Consultant Psychiatrist Centre for Anxiety Disorders and Trauma, The Maudsley Hospital and Visiting Senior Lecturer, Institute of Psychiatry and Chair of the NICE Evidence Update on OCD [email protected] Dr Oliver Suendermann Clinical Psychologist at the Anxiety Disorders Residential Unit Standardization would assist in the reporting of clinical trials or protocols; and comparing similar studies in meta-analysis. Specifically a common description would improve the Consort Statement for Non-Pharmacological Interventions that requires “Precise details of the interventions intended for each group and how and when they were actually administered”. However there is no standardized method of reporting different formats or intensity of a psychological therapy and it is extremely difficult to extract this information in a systematic review. The aim of this review is (1) to scope the different ways of delivering psychological therapies, (2) to recommend a multi-dimensional description for reporting for the delivery of psychological therapies (3) sample how many controlled trials currently provide the information required in a format that can be easily obtained. The review should lead to a publication and perhaps a standard of reporting to be adopted in future protocols and trials of psychotherapy. [email protected] hs.uk 11. Are blood-based protein biomarkers for Alzheimer’s disease also involved in other brain disorders? Dr Martina Sattlecker Researcher, Bioinformatician Institute of Psychiatry The number of people with dementia, especially Alzheimer’s disease (AD), is rapidly growing. Currently there is no fast, objective and accurate method for an early diagnosis and thus the search for biomarkers in blood is a fast growing research area. Similarly, researchers are turning to the blood proteome for markers of other brain disorders. So far no attempt has been made to review whether the protein biomarkers reported in the literature are specific or are indicative of general brain disorder. [email protected] Dr Steven Kiddle Researcher Institute of Psychiatry [email protected] Recently we executed a literature search and summarised the most frequently reported AD protein biomarkers in blood. The next step will be to identify if these AD proteins are specific to AD or whether they are also involved in other dementia types and mental illnesses, such as Lewy body dementia, Parkinson’s disease, Schizophrenia and Autism. This literature review will show if blood-based protein markers are AD specific or involved in various brain disorders. 12. Searching for unpublished trials of anti-psychotics in Obsessive Compulsive Disorder Anti-psychotic drugs are often prescribed “off-license” by clinicians to augment a selective serotonergic reuptake inhibitor (SSRI) anti-depressant for people with severe Obsessive Compulsive Disorder (OCD) who are refractory to SSRIs and cognitive behaviour therapy. The evidence base for adding an anti-psychotic is limited, but as a class they are recommended in the NICE guidelines for OCD (2006). More recently a Cochrane review (Komasssi, et al 2010) published a metaanalysis and suggested there was limited evidence for some specific anti-psychotics in the short term. The NICE Evidence Update (2013) recently searched for any new evidence in the past 3 years and has identified all the published controlled trials. However, off-label uses may be particularly vulnerable to selective data publication, which can lead to exaggeration of treatment benefits (Goldacre, 2012). The question for this study is whether there are other unpublished data that should be included in a meta-analysis of anti-psychotic augmentation, as it may lead to different conclusions than the NICE recommendations. This project will explore various methods for accessing unpublished results, and document barriers to access. There are three objectives to this study: (1) to determine if there are any unpublished studies or data on adverse effects or outcomes in long term on anti-psychotics in OCD that have not been published (2) to document barriers to access to these results (3) to summarise the results of the trials that have been done and to document their shortcomings. Method: We will first tabulate all the published RCTs of antipsychotics used in OCD identified from the NICE Evidence Update on OCD (2013), the NICE Clinical Guidelines on OCD and BDD (2006) and 4 published systematic reviews (Fineberg et al, 2006; Bloch et al, 2006; Komossa, K, et al (2010) and Zhornitsky et al (2013). These currently total about 15 RCTs including risperidone, quetapine, aripiprazole, olanzapine; amisulpiride and amisulpiride. The list of RCTs will facilitate cross-checking against various registries including the 1) European Medicine Agency (EMA), 2) US Food and Drug Administration (FDA), 3) Medicines Healthcare and Regulations Agency Database (MHRA) 4) the WHO International Clinical trials registry 5) EU and industry registries and contacting pharmaceutical companies directly (Chan et al, 2012). Output: If new data is found then we will conduct a new meta-analysis that combines the published and unpublished data and submit for publication and submit our findings to NICE. If no further unpublished trials are found, a publication would set out the different avenues for getting access to results, the barriers encountered when searching for unpublished trials for unlicensed uses of a drug, and the shortcomings in systems, regulations and voluntary codes. 13. Is getting old like a bit like having a cingulotomy? The cingulum is a bundle of white matter fibres that runs front to back on the inner surface of the cerebral hemisphere. It connects to the anterior cingulate cortex, the function of which remains a hot topic in modern neuroscience. Cutting the cingulum connections – or cingulotomy – is a form of psychosurgery still used to treat depression and obsessive compulsive disorder. Stroke can also damage these connections. Recently, we have shown that alteration in these connections as we grow older leads to problems with cognitive control (Metzler-Baddeley et al. J Neurosci 2012). The purpose of this review will be to revisit the cingulotomy literature in the light of recent findings about cingulum function. Do those treated with cingulotomy develop the same problems as those in whom the cingulum is damaged by stroke? Are the benefits of cingulotomy shared by some patients with stroke or as a result of ageing? Is it possible to devise a more precise procedure? Dr David Veale Consultant Psychiatrist Centre for Anxiety Disorders and Trauma, The Maudsley Hospital and Visiting Senior Lecturer, Institute of Psychiatry and Chair of the NICE Evidence Update on OCD [email protected] Dr Ben Goldacre Wellcome Research Fellow, London School of Hygiene and Tropical Medicine, author of “Bad Pharma” Dr Michael O’Sullivan Senior Lecturer, Cognitive Neuroscience Institute of Psychiatry [email protected] Dr Rob Weeks Consultant Neurologist, Lead Clinician for Stroke King’s College Hospital [email protected] 14. Cognitive detective work on the stroke unit Cognitive problems represent the greatest area of unmet need for stroke survivors. Most commonly, patients complain of poor memory or poor concentration. Despite the importance, very little is known about how cognitive deficits should be identified on stroke units. Most of the tests used were developed in memory clinics or in Alzheimer’s disease. Stroke brings particular problems however: tests based on language may be difficult to administer and it may be difficult to pay attention to demanding tasks in the busy, noisy environment of a stroke unit. Also, some deficits after stroke are temporary and therefore not relevant to longer term problems. This project will review approaches that have been evaluated early after stroke in a stroke unit setting. In particular, it will aim to identify those tests that have helped to guide rehabilitation or predict longer-term outcome. What use could be made of technology such as smart phones or tablets? This project offers the opportunity to truly shape the way a problem is approached in a leading stroke unit. 15. Exploring the association between patient delay in presentation and Dr Michael O’Sullivan Senior Lecturer, Cognitive Neuroscience Institute of Psychiatry [email protected] Dr Rob Weeks Consultant Neurologist, Lead Clinician for Stroke King’s College Hospital [email protected] Maja Niksic PhD student, Department survival in lung and/or colorectal cancer of Psychological Medicine, Early detection of cancer could increase the chances for successful treatment Promoting Early Cancer and improved survival. However, once cancer symptoms occur, the effects of Presentation Group patient delay on survival are not clear. Approximately 40% of people delay [email protected] consulting a doctor once they have detected an unexplained symptom, which could lead to cancer diagnosis (Cancer Research UK, 2012). The association between patient delay in presentation and cancer survival has been the (2 students) subject of interest and considerable controversy for many years. There is reliable evidence to suggest that longer patient delays in presentation are associated with lower survival in breast cancer (Arndt et al., 2002; Richards et al., 1999). However, inconclusive evidence exists for association between patient delay and survival in colorectal (Kiran & Glass, 2002) and lung cancer (Jensen et al., 2002; O'Rourke & Edwards, 2000). The aim of this project is to explore the current evidence of the relationship between patient delays in presentation and survival in lung and colorectal cancers. Objectives of the review are: A) to explore the quality and strength of the evidence of this association; B) to explore other, potentially confounding factors of the association between patient delay in presentation and survival in lung and colorectal cancer, such as patients’ age or stage of diagnosis; and, C) to explore whether duration of patient delay (up to 3 weeks/ up to 6 months/ up to one year/ more than a year) is associated with survival in lung and colorectal cancer. The project will involve the systematic review of literature using databases, such as MEDLINE, Embase, PsycInfo and Cochrane Library. There is a possibility to focus the project on one type of cancer only, such as to explore only lung, or only colorectal cancer. Students are strongly encouraged to develop a manuscript for publication at the end of the project. 16. Differential roles for the dorsal and ventral hippocampus in Alzheimer’s disease Dr Sandrine Thuret Lecturer in Neural Stem Cell Research Neuroscience Further details to be discussed with supervisor [email protected] k 17. Number sense and Mathematical abilities. This is relevant for studies on Autistic Spectrum Disorder and Learning abilities/disabilities. Further details to be discussed with supervisor. Dr Karim Malki Researcher SGDP [email protected] 18. ADHD: The latest genetic findings TBC Dr Karim Malki Researcher SGDP [email protected] 19. Computational Methods for exploring genome-wide data Lately there have been many advances in the field of data-mining and Machine Learning and it would be nice to summarise the current efforts and gain a future perspective on how these methods will impact the field in the next 5 years. Dr Karim Malki Researcher SGDP [email protected]