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  • Healthy minds from 0-100 years: Optimising the use of European brain imaging cohorts (“Lifebrain”)

    2 April 2018

    The main objective of “Lifebrain” is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5,000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total. By linking these data to other databases and biobanks, including birth registries, national and regional archives, and by enriching them with a new online data collection and novel measures, we will address the risk factors and protective factors of BCM health. We will identify pathways through which risk and protective factors work and their moderators. Exploiting existing European infrastructures and initiatives, we hope to make major conceptual, methodological and analytical contributions towards large integrative cohorts and their efficient exploitation. We will thus provide novel information on BCM health maintenance, as well as the onset and course of BCM disorders. This will lay a foundation for earlier diagnosis of brain disorders, aberrant development and decline of BCM health, and translate into future preventive and therapeutic strategies. Aiming to improve clinical practice and public health we will work with stakeholders and health authorities, and thus provide the evidence base for prevention and intervention.

  • Teacher Competence in Mindfulness-Based Cognitive Therapy for Depression and Its Relation to Treatment Outcome.

    5 March 2018

    As mindfulness-based cognitive therapy (MBCT) becomes an increasingly mainstream approach for recurrent depression, there is a growing need for practitioners who are able to teach MBCT. The requirements for being competent as a mindfulness-based teacher include personal meditation practice and at least a year of additional professional training. This study is the first to investigate the relationship between MBCT teacher competence and several key dimensions of MBCT treatment outcomes. Patients with recurrent depression in remission (N = 241) participated in a multi-centre trial of MBCT, provided by 15 teachers. Teacher competence was assessed using the Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC) based on two to four randomly selected video-recorded sessions of each of the 15 teachers, evaluated by 16 trained assessors. Results showed that teacher competence was not significantly associated with adherence (number of MBCT sessions attended), possible mechanisms of change (rumination, cognitive reactivity, mindfulness, and self-compassion), or key outcomes (depressive symptoms at post treatment and depressive relapse/recurrence during the 15-month follow-up). Thus, findings from the current study indicate no robust effects of teacher competence, as measured by the MBI:TAC, on possible mediators and outcome variables in MBCT for recurrent depression. Possible explanations are the standardized delivery of MBCT, the strong emphasis on self-reliance within the MBCT learning process, the importance of participant-related factors, the difficulties in assessing teacher competence, the absence of main treatment effects in terms of reducing depressive symptoms, and the relatively small selection of videotapes. Further work is required to systematically investigate these explanations.

  • Cost and Outcome of BehaviouRal Activation (COBRA): a randomised controlled trial of behavioural activation versus cognitive-behavioural therapy for depression.

    5 March 2018

    Depression is a common, debilitating and costly disorder. The best-evidenced psychological therapy - cognitive-behavioural therapy (CBT) - is complex and costly. A simpler therapy, behavioural activation (BA), may be an effective alternative.To determine the clinical effectiveness and cost-effectiveness of BA compared with CBT for depressed adults at 12 and 18 months' follow-up, and to investigate the processes of treatments.Randomised controlled, non-inferiority trial stratified by depression severity, antidepressant use and recruitment site, with embedded process evaluation; and randomisation by remote computer-generated allocation.Three community mental health services in England.Adults aged ≥ 18 years with major depressive disorder (MDD) recruited from primary care and psychological therapy services.BA delivered by NHS junior mental health workers (MHWs); CBT by NHS psychological therapists.Primary: depression severity (as measured via the Patient Health Questionnaire-9; PHQ-9) at 12 months. Secondary: MDD status; number of depression-free days; anxiety (as measured via the Generalised Anxiety Disorder-7); health-related quality of life (as measured via the Short Form questionnaire-36 items) at 6, 12 and 18 months; and PHQ-9 at 6 and 18 months, all collected by assessors blinded to treatment allocation. Non-inferiority margin was 1.9 PHQ-9 points. We undertook intention-to-treat (ITT) and per protocol (PP) analyses. We explored cost-effectiveness by collecting direct treatment and other health- and social-care costs and calculating quality-adjusted life-years (QALYs) using the EuroQol-5 Dimensions, three-level version, at 18 months.We recruited 440 participants (BA, n = 221; CBT, n = 219); 175 (79%) BA and 189 (86%) CBT participants provided ITT data and 135 (61%) BA and 151 (69%) CBT participants provided PP data. At 12 months we found that BA was non-inferior to CBT {ITT: CBT 8.4 PHQ-9 points [standard deviation (SD) 7.5 PHQ-9 points], BA 8.4 PHQ-9 points (SD 7.0 PHQ-9 points), mean difference 0.1 PHQ-9 points, 95% confidence interval (CI) -1.3 to 1.5 PHQ-9 points, p = 0.89; PP: CBT 7.9 PHQ-9 points (SD 7.3 PHQ-9 points), BA 7.8 PHQ-9 points (SD 6.5 PHQ-9 points), mean difference 0.0 PHQ-9 points, 95% CI -1.5 to 1.6 PHQ-9 points, p = 0.99}. We found no differences in secondary outcomes. We found a significant difference in mean intervention costs (BA, £975; CBT, £1235; p < 0.001), but no differences in non-intervention (hospital, community health, social care and medication costs) or total (non-intervention plus intervention) costs. Costs were lower and QALY outcomes better in the BA group, generating an incremental cost-effectiveness ratio of -£6865. The probability of BA being cost-effective compared with CBT was almost 80% at the National Institute for Health and Care Excellence's preferred willingness-to-pay threshold of £20,000-30,000 per QALY. There were no trial-related adverse events.In this pragmatic trial many depressed participants in both groups were also taking antidepressant medication, although most had been doing so for a considerable time before entering the trial. Around one-third of participants chose not to complete a PP dose of treatment, a finding common in both psychotherapy trials and routine practice.We found that BA is as effective as CBT, more cost-effective and can be delivered by MHWs with no professional training in psychological therapies.Settings and countries with a paucity of professionally qualified psychological therapists, might choose to investigate the delivery of effective psychological therapy for depression without the need to develop an extensive and costly professional infrastructure.Current Controlled Trials ISRCTN27473954.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 46. See the NIHR Journals Library website for further project information.

  • Suicide is a complex problem that requires a range of prevention initiatives and methods of evaluation.

    2 April 2018

    A range of factors can contribute to suicide, which means that a multifactorial approach to suicide prevention is necessary. Whereas randomised controlled trials may be suitable for evaluation of some interventions, others require different approaches for assessment of their impact. Also, suicide itself will not always be the most feasible outcome measure.

  • Spectrum of Fates: a new approach to the study of the developing zebrafish retina.

    2 February 2018

    The ability to image cells live and in situ as they proliferate and differentiate has proved to be an invaluable asset to biologists investigating developmental processes. Here, we describe a Spectrum of Fates approach that allows the identification of all the major neuronal subtypes in the zebrafish retina simultaneously. Spectrum of Fates is based on the combinatorial expression of differently coloured fluorescent proteins driven by the promoters of transcription factors that are expressed in overlapping subsets of retinal neurons. Here, we show how a Spectrum of Fates approach can be used to assess various aspects of neural development, such as developmental waves of differentiation, neuropil development, lineage tracing and hierarchies of fates in the developing zebrafish retina.

  • Microcephaly models in the developing zebrafish retinal neuroepithelium point to an underlying defect in metaphase progression.

    15 February 2018

    Autosomal recessive primary microcephaly (MCPH) is a congenital disorder characterized by significantly reduced brain size and mental retardation. Nine genes are currently known to be associated with the condition, all of which encode centrosomal or spindle pole proteins. MCPH is associated with a reduction in proliferation of neural progenitors during fetal development. The cellular mechanisms underlying the proliferation defect, however, are not fully understood. The zebrafish retinal neuroepithelium provides an ideal system to investigate this question. Mutant or morpholino-mediated knockdown of three known MCPH genes (stil, aspm and wdr62) and a fourth centrosomal gene, odf2, which is linked to several MCPH proteins, results in a marked reduction in head and eye size. Imaging studies reveal a dramatic rise in the fraction of proliferating cells in mitosis in all cases, and time-lapse microscopy points to a failure of progression through prometaphase. There was also increased apoptosis in all the MCPH models but this appears to be secondary to the mitotic defect as we frequently saw mitotically arrested cells disappear, and knocking down p53 apoptosis did not rescue the mitotic phenotype, either in whole retinas or clones.

  • Cellular requirements for building a retinal neuropil.

    2 February 2018

    How synaptic neuropil is formed within the CNS is poorly understood. The retinal inner plexiform layer (IPL) is positioned between the cell bodies of amacrine cells (ACs) and retinal ganglion cells (RGCs). It consists of bipolar cell (BC) axon terminals that synapse on the dendrites of ACs and RGCs intermingled with projections from Müller glia (MG). We examined whether any of these cellular processes are specifically required for the formation of the IPL. Using genetic and pharmacological strategies, we eliminated RGCs, ACs, and MG individually or in combination. Even in the absence of all of these partner cells, an IPL-like neuropil consisting of only BC axon terminals still forms, complete with presynaptic specializations and sublaminar organization. Previous studies have shown that an IPL can form in the complete absence of BCs; therefore, we conclude that neither presynaptic nor postsynaptic processes are individually essential for the formation of this synaptic neuropil.

  • Origin and determination of inhibitory cell lineages in the vertebrate retina.

    16 March 2018

    Multipotent progenitors in the vertebrate retina often generate clonally related mixtures of excitatory and inhibitory neurons. The postmitotically expressed transcription factor, Ptf1a, is essential for all inhibitory fates in the zebrafish retina, including three types of horizontal and 28 types of amacrine cell. Here, we show that specific types of inhibitory neurons arise from the cell-autonomous influence of Ptf1a in the daughters of fate-restricted progenitors, such as Ath5 or Vsx1/2-expressing progenitors, and that in the absence of Ptf1a, cells that would have become these specific inhibitory subtypes revert to the histogenetically appropriate excitatory subtypes of the same lineage. Altered proportions of amacrine subtypes respecified by the misexpression of Ptf1a in the Ath5 lineage suggest that Ath5-expressing progenitors are biased, favoring the generation of some subtypes more than others. Yet the full array of inhibitory cell subtypes in Ath5 mutants implies the existence of Ath5-independent factors involved in inhibitory cell specification. We also show that an extrinsic negative feedback on the expression of Ptf1a provides a control mechanism by which the number of any and all types of inhibitory cells in the retina can be regulated in this lineage-dependent way.

  • Growth-factor-dependent phosphorylation of Bim in mitosis.

    15 February 2018

    The regulation of survival and cell death is a key determinant of cell fate. Recent evidence shows that survival and death machineries are regulated along the cell cycle. In the present paper, we show that BimEL [a BH3 (Bcl-2 homology 3)-only member of the Bcl-2 family of proteins; Bim is Bcl-2-interacting mediator of cell death; EL is the extra-long form] is phosphorylated in mitosis. This post-translational modification is dependent on MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase) and growth factor signalling. Interestingly, FGF (fibroblast growth factor) signalling seems to play an essential role in this process, since, in the presence of serum, inhibition of FGF receptors abrogated phosphorylation of Bim in mitosis. Moreover, we have shown bFGF (basic FGF) to be sufficient to induce phosphorylation of Bim in serum-free conditions in any phase of the cell cycle, and also to significantly rescue cells from serum-deprivation-induced apoptosis. Our results show that, in mitosis, Bim is phosphorylated downstream of growth factor signalling in a MEK-dependent manner, with FGF signalling playing an important role. We suggest that phosphorylation of Bim is a decisive step for the survival of proliferating cells.

  • Tsukushi modulates Xnr2, FGF and BMP signaling: regulation of Xenopus germ layer formation.

    29 March 2018

    BACKGROUND: Cell-cell communication is essential in tissue patterning. In early amphibian development, mesoderm is formed in the blastula-stage embryo through inductive interactions in which vegetal cells act on overlying equatorial cells. Members of the TGF-beta family such as activin B, Vg1, derrière and Xenopus nodal-related proteins (Xnrs) are candidate mesoderm inducing factors, with further activity to induce endoderm of the vegetal region. TGF-beta-like ligands, including BMP, are also responsible for patterning of germ layers. In addition, FGF signaling is essential for mesoderm formation whereas FGF signal inhibition has been implicated in endoderm induction. Clearly, several signaling pathways are coordinated to produce an appropriate developmental output; although intracellular crosstalk is known to integrate multiple pathways, relatively little is known about extracellular coordination. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that Xenopus Tsukushi (X-TSK), a member of the secreted small leucine rich repeat proteoglycan (SLRP) family, is expressed in ectoderm, endoderm, and the organizer during early development. We have previously reported that X-TSK binds to and inhibits BMP signaling in cooperation with chordin. We now demonstrate two novel interactions: X-TSK binds to and inhibits signaling by FGF8b, in addition to binding to and enhancement of Xnr2 signaling. This signal integration by X-TSK at the extracellular level has an important role in germ layer formation and patterning. Vegetally localized X-TSK potentiates endoderm formation through coordination of BMP, FGF and Xnr2 signaling. In contrast, X-TSK inhibition of FGF-MAPK signaling blocks ventrolateral mesoderm formation, while BMP inhibition enhances organizer formation. These actions of X-TSK are reliant upon its expression in endoderm and dorsal mesoderm, with relative exclusion from ventrolateral mesoderm, in a pattern shaped by FGF signals. CONCLUSIONS/SIGNIFICANCE: Based on our observations, we propose a novel mechanism by which X-TSK refines the field of positional information by integration of multiple pathways in the extracellular space.

  • From lab bench to green bench

    9 December 2015

    Dr Jessica Ash, from the Department of Psychiatry visited MP George Freeman, the life sciences minister, at the House of Commons for a week in Westminster.

  • Human trials suggest ‘rescued’ drug could be safer treatment for bipolar disorder

    9 December 2015

    A drug destined for the scrap heap has been rescued by Oxford scientists, who may have found it a new role in treating bipolar disorder.

  • Reported self-inflicted harm cases have steadily risen in UK since 2008

    9 May 2016

    The number of cases of self-harm presenting to hospitals in England has risen steadily since 2008, especially among men, reveals research co-ordinated by the Centre for Suicide Research at Oxford University Department of Psychiatry, published in the online journal BMJ Open.

  • Professor Michael Sharpe is named as Psychiatrist of the Year

    7 November 2014

    Professor Sharpe has been named as Psychiatrist of the Year at the Royal College of Psychiatrists Awards Ceremony in London

  • Self-help from the stands

    18 October 2013

    Gill Oliver probes mind and motivations of the Watford FC-supporting Oxford University Professor of Clinical Psychology

  • Simple blood test gives early warning of Alzheimer's

    8 July 2014

    BBC News online, 08/07/14, James Gallagher: Scientists have made a ‘major step forward’ in developing a blood test to predict the onset of Alzheimer's disease. Research in more than 1,000 people has identified a set of proteins in the blood which can predict the start of the dementia with 87% accuracy. The findings, published in the journal Alzheimer's & Dementia, will be used to improve trials for new dementia drugs.

  • Largest epidemiological study of epilepsy and psychiatric disorders

    22 July 2013

    In a recent Lancet paper, Seena Fazel together with Achim Wolf and Charles Newton from this department, reports that "people with epilepsy are 11 times more likely to die prematurely than the general population, and the risk appears to be substantially higher for individuals with common co-existing psychiatric illnesses." He adds: "standard psychiatric checks could help reduce the risk of premature deaths in people with epilepsy."

  • Congratulations Kate!

    22 July 2013

    Dr Kate Saunders has been awarded the Johnstone & Florence Stoney studentship by the British Federation of Women Graduates after competitive interview. The Studentship will be officially awarded on Thursday, October 17th before the Sybil Campbell Collection Annual Lecture at the University Women’s Club, in 2 Audley Square, Mayfair.

  • Psychological Benefits for Prisoners doing Yoga

    11 July 2013

    Yoga could help address mental health problems in prisons Yoga can improve mood and mental wellbeing among prisoners, an Oxford University study suggests, and may also have an effect on impulsive behaviour.

  • Imbalance of ADHD diagnosis in the US

    23 November 2015

    Higher numbers of diagnosis exist in some affluent populations, while in poor white populations and ethnic minorities there is under-diagnosis, says Professor Ilina Singh

  • Improving lifelong cognitive health through physical exercise and cognitive stimulation

    1 November 2012

    The human brain has a remarkable capacity to learn and adapt. This ability is strongly influenced by many factors, including how active we are - both physically and mentally.

  • Oxford Parkinson's Disease Centre

    1 November 2012

    The Oxford Parkinson's Disease Centre (OPDC) is a grouping of scientists and clinicians launched in February 2010 following the award of the Monument Trust Discovery Award to Oxford University

  • Oxford Dementia and Ageing Research

    1 November 2012

    Oxford Dementia and Ageing Research is a consortium of clinical and basic scientists who work on various aspects of translational dementia and ageing research

  • We are available for media comment

    1 November 2012

    Please use the content details at the top of this page to get in touch

  • Important Links

    1 November 2012

  • Traumatic brain injury (TBI) as a substantial cause of disability (Seena Fazel)

    16 June 2013

    Traumatic brain injury (TBI) is a substantial cause of disability with high societal costs worldwide. In the US, where surveillance started in 1989, 3.2 million persons or 1% of the population have sustained a TBI in their lifetime. Similarly large numbers have been reported in European countries. The public health burden may increase in the next few decades, as road traffic accidents, a leading cause of TBI and currently the ninth largest contributor to disability-adjusted living years globally, are estimated to become the third largest contributor by 2030 with a particularly large rise in middle income countries. One high risk group are prisoners, where high rates of TBI have been reported, including in juvenile prisons, and where little is known about this TBI contributes to adverse outcomes following release.

  • The influence of stress and genotype on the response to a dopaminergic drug (Paul Harrison & Liz Tunbridge)

    16 June 2013

    Tolcapone is an inhibitor of the dopamine-metabolizing enzyme catechol-o-methyltransferase (COMT), used in the adjunctive treatment of Parkinson’s disease. Our recent study (Farrell SM et al, Biological Psychiatry 2012; 71: 538-544), and others, show that it also has effects in healthy subjects on cognition and risk taking.

  • Parents and Carers of Young People who Self-harm:Summary of Research Findings for Clinicians

    14 January 2016

    A guide for clinicians describing the key results of a qualitative study designed to explore explore the experiences and perceptions of parents/carers of young people who self-harm, and aims to assist clinicians in helping families navigate through this experience.

  • Research Seminar

    14 October 2013

    Seminars this term will take place on the 4th May and the 1st June 2016

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  • Files

    30 June 2017

  • Research in Autism

    15 April 2013

    Many groups throughout the University of Oxford and the Oxford area.

  • Service Providers for Autism

    15 April 2013

    description of clinical column

  • News and meetings

    15 April 2013

    Short descripton

  • Research Projects

    30 June 2017

    NIHR Programme Grant- A collaborative programme of research to support the National Suicide Prevention Strategy [+ Additional page attached as Word doc] Multicentre Study of Self-harm in England- A national collaboration to provide a basis for studies of self-harm in England [+ Additional page attached as Word doc Multicentre_for_dept_website.docx] Wellcome Trust Safer Storage of Pesticides Project

  • Subgroups

    26 September 2014

    We have a number of subgroups within the larger Child and Adolescent Group.

  • Participants needed for emotional processing drug study- Ethics Ref: R50651/RE001

    4 September 2017

    The study mainly involves computer-based psychological tasks on emotional and cognitive processing and the taking of blood samples.

  • Are you interested in how the brain works? Men needed!

    18 October 2016

    If you take part, we will ask you to: - Provide a cheek swab (to see which form of the gene you have) then, if suitable, come to the lab and: - Take a single dose of a drug or a dummy pill; - Fill in some questionnaires and give samples of saliva; - Complete tasks of mental maths, memory and reward, while in an MRI brain scanner. The study will take one afternoon (around 3.5 hours).

  • Brain Stimulation Study

    30 January 2018

    We are looking for healthy volunteers to improve our understanding of how the brain is organised and how it processes information during motor learning. Transcranial Direct Current Stimulation (TDCS) is a form of neurostimulation that uses constant, low current delivered to the brain area of interest via sensors on the scalp. Participants may experience some discomfort during TDCS. This study involves two visits to the Department of Psychiatry in Oxford. Each session will take around two hours of your time.

  • Eating Concerns and Compulsivity

    22 August 2017

    We are currently looking for people that fit into one of two: healthy people who have been recovered from anorexia nervosa for over a year, and those who think a lot about their eating, weight and shape. You should be a healthy female aged between 18 and 45 years. We are looking for women who do not have any current health or psychiatric problems. We will be asking you to do some questionnaires and complete two computer tasks, which measure behaviour thought to be related to compulsivity. Compulsivity is repetitively performing actions which aren’t rewarding or good for you. We will also non-invasively measure your pupils during one of the tasks.