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  • Clinical Insight Into Latent Variables of Psychiatric Questionnaires for Mood Symptom Self-Assessment.

    18 December 2017

    BACKGROUND: We recently described a new questionnaire to monitor mood called mood zoom (MZ). MZ comprises 6 items assessing mood symptoms on a 7-point Likert scale; we had previously used standard principal component analysis (PCA) to tentatively understand its properties, but the presence of multiple nonzero loadings obstructed the interpretation of its latent variables. OBJECTIVE: The aim of this study was to rigorously investigate the internal properties and latent variables of MZ using an algorithmic approach which may lead to more interpretable results than PCA. Additionally, we explored three other widely used psychiatric questionnaires to investigate latent variable structure similarities with MZ: (1) Altman self-rating mania scale (ASRM), assessing mania; (2) quick inventory of depressive symptomatology (QIDS) self-report, assessing depression; and (3) generalized anxiety disorder (7-item) (GAD-7), assessing anxiety. METHODS: We elicited responses from 131 participants: 48 bipolar disorder (BD), 32 borderline personality disorder (BPD), and 51 healthy controls (HC), collected longitudinally (median [interquartile range, IQR]: 363 [276] days). Participants were requested to complete ASRM, QIDS, and GAD-7 weekly (all 3 questionnaires were completed on the Web) and MZ daily (using a custom-based smartphone app). We applied sparse PCA (SPCA) to determine the latent variables for the four questionnaires, where a small subset of the original items contributes toward each latent variable. RESULTS: We found that MZ had great consistency across the three cohorts studied. Three main principal components were derived using SPCA, which can be tentatively interpreted as (1) anxiety and sadness, (2) positive affect, and (3) irritability. The MZ principal component comprising anxiety and sadness explains most of the variance in BD and BPD, whereas the positive affect of MZ explains most of the variance in HC. The latent variables in ASRM were identical for the patient groups but different for HC; nevertheless, the latent variables shared common items across both the patient group and HC. On the contrary, QIDS had overall very different principal components across groups; sleep was a key element in HC and BD but was absent in BPD. In GAD-7, nervousness was the principal component explaining most of the variance in BD and HC. CONCLUSIONS: This study has important implications for understanding self-reported mood. MZ has a consistent, intuitively interpretable latent variable structure and hence may be a good instrument for generic mood assessment. Irritability appears to be the key distinguishing latent variable between BD and BPD and might be useful for differential diagnosis. Anxiety and sadness are closely interlinked, a finding that might inform treatment effects to jointly address these covarying symptoms. Anxiety and nervousness appear to be amongst the cardinal latent variable symptoms in BD and merit close attention in clinical practice.

  • The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Acute and long-term treatment of mixed states in bipolar disorder.

    16 February 2018

    OBJECTIVES: Although clinically highly relevant, the recognition and treatment of bipolar mixed states has played only an underpart in recent guidelines. This WFSBP guideline has been developed to supply a systematic overview of all scientific evidence pertaining to the acute and long-term treatment of bipolar mixed states in adults. METHODS: Material used for these guidelines is based on a systematic literature search using various data bases. Their scientific rigour was categorised into six levels of evidence (A-F), and different grades of recommendation to ensure practicability were assigned. We examined data pertaining to the acute treatment of manic and depressive symptoms in bipolar mixed patients, as well as data pertaining to the prevention of mixed recurrences after an index episode of any type, or recurrence of any type after a mixed index episode. RESULTS: Manic symptoms in bipolar mixed states appeared responsive to treatment with several atypical antipsychotics, the best evidence resting with olanzapine. For depressive symptoms, addition of ziprasidone to treatment as usual may be beneficial; however, the evidence base is much more limited than for the treatment of manic symptoms. Besides olanzapine and quetiapine, valproate and lithium should also be considered for recurrence prevention. LIMITATIONS: The concept of mixed states changed over time, and recently became much more comprehensive with the release of DSM-5. As a consequence, studies in bipolar mixed patients targeted slightly different bipolar subpopulations. In addition, trial designs in acute and maintenance treatment also advanced in recent years in response to regulatory demands. CONCLUSIONS: Current treatment recommendations are still based on limited evidence, and there is a clear demand for confirmative studies adopting the DSM-5 specifier with mixed features concept.

  • Dynamic Imaging of the Eye, Optic Nerve, and Extraocular Muscles With Golden Angle Radial MRI.

    21 December 2017

    Purpose: The eye and its accessory structures, the optic nerve and the extraocular muscles, form a complex dynamic system. In vivo magnetic resonance imaging (MRI) of this system in motion can have substantial benefits in understanding oculomotor functioning in health and disease, but has been restricted to date to imaging of static gazes only. The purpose of this work was to develop a technique to image the eye and its accessory visual structures in motion. Methods: Dynamic imaging of the eye was developed on a 3-Tesla MRI scanner, based on a golden angle radial sequence that allows freely selectable frame-rate and temporal-span image reconstructions from the same acquired data set. Retrospective image reconstructions at a chosen frame rate of 57 ms per image yielded high-quality in vivo movies of various eye motion tasks performed in the scanner. Motion analysis was performed for a left-right version task where motion paths, lengths, and strains/globe angle of the medial and lateral extraocular muscles and the optic nerves were estimated. Results: Offline image reconstructions resulted in dynamic images of bilateral visual structures of healthy adults in only ∼15-s imaging time. Qualitative and quantitative analyses of the motion enabled estimation of trajectories, lengths, and strains on the optic nerves and extraocular muscles at very high frame rates of ∼18 frames/s. Conclusions: This work presents an MRI technique that enables high-frame-rate dynamic imaging of the eyes and orbital structures. The presented sequence has the potential to be used in furthering the understanding of oculomotor mechanics in vivo, both in health and disease.

  • Quantitative characterization of optic nerve atrophy in patients with multiple sclerosis.

    7 December 2017

    BACKGROUND: Optic neuritis (ON) is one of the most common presentations of multiple sclerosis (MS). Magnetic resonance imaging (MRI) of the optic nerves is challenging because of retrobulbar motion, orbital fat and susceptibility artifacts from maxillary sinuses; therefore, axonal loss is investigated with the surrogate measure of a single heuristically defined point along the nerve as opposed to volumetric investigation. OBJECTIVE: The objective of this paper is to derive optic nerve volumetrics along the entire nerve length in patients with MS and healthy controls in vivo using high-resolution, clinically viable MRI. METHODS: An advanced, isotropic T2-weighted turbo spin echo MRI was applied to 29 MS patients with (14 patients ON+) or without (15 patients ON-) history of ON and 42 healthy volunteers. An automated tool was used to estimate and compare whole optic nerve and surrounding cerebrospinal fluid radii along the length of the nerve. RESULTS AND CONCLUSION: Only ON+ MS patients had a significantly reduced optic nerve radius compared to healthy controls in the central segment of the optic nerve. Using clinically available MRI methods, we show and quantify ON volume loss for the first time in MS patients.

  • Pool size ratio of the substantia nigra in Parkinson's disease derived from two different quantitative magnetization transfer approaches.

    15 February 2018

    PURPOSE: We sought to measure quantitative magnetization transfer (qMT) properties of the substantia nigra pars compacta (SNc) in patients with Parkinson's disease (PD) and healthy controls (HCs) using a full qMT analysis and determine whether a rapid single-point measurement yields equivalent results for pool size ratio (PSR). METHODS: Sixteen different MT-prepared MRI scans were obtained at 3 T from 16 PD patients and eight HCs, along with B1, B0, and relaxation time maps. Maps of PSR, free and macromolecular pool transverse relaxation times ([Formula: see text], [Formula: see text]) and rate of MT exchange between pools (kmf) were generated using a full qMT model. PSR maps were also generated using a single-point qMT model requiring just two MT-prepared images. qMT parameter values of the SNc, red nucleus, cerebral crus, and gray matter were compared between groups and methods. RESULTS: PSR of the SNc was the only qMT parameter to differ significantly between groups (p < 0.05). PSR measured via single-point analysis was less variable than with the full MT model, provided slightly better differentiation of PD patients from HCs (area under curve 0.77 vs. 0.75) with sensitivity of 0.75 and specificity of 0.87, and was better than transverse relaxation time in distinguishing PD patients from HCs (area under curve 0.71, sensitivity 0.87, and specificity 0.50). CONCLUSION: The increased PSR observed in the SNc of PD patients may provide a novel biomarker of PD, possibly associated with an increased macromolecular content. Single-point PSR mapping with reduced variability and shorter scan times relative to the full qMT model appears clinically feasible.

  • SlowMo, a digital therapy targeting reasoning in paranoia, versus treatment as usual in the treatment of people who fear harm from others: study protocol for a randomised controlled trial.

    28 January 2018

    BACKGROUND: Paranoia is one of the most common symptoms of schizophrenia-spectrum disorders, and is associated with significant distress and disruption to the person's life. Developing more effective and accessible psychological interventions for paranoia is a clinical priority. Our research team has approached this challenge in two main ways: firstly, by adopting an interventionist causal approach to increase effectiveness and secondly, by incorporating user-centred inclusive design methods to enhance accessibility and usability. Our resultant new digital intervention, SlowMo, intensively targets a reasoning style associated with paranoia, fast thinking, characterised by jumping to conclusions and belief inflexibility. It consists of an easy-to-use, enjoyable and memorable digital interface. An interactive web-based app facilitates delivery of face-to-face meetings which is then synchronised with an innovative mobile app for use in daily life. METHODS/DESIGN: We aim to test the clinical efficacy of SlowMo over 24 weeks to determine the mechanisms through which it reduces paranoia, and to identify participant characteristics that moderate its effectiveness. In a parallel-group randomised controlled trial, with 1:1 allocation, 360 participants with distressing persecutory beliefs will be independently randomised to receive either the SlowMo intervention added to treatment as usual (TAU) or TAU, using randomly varying permuted blocks, stratified by paranoia severity and site. Research workers will be blind to therapy allocation. The primary outcome is paranoia severity over 24 weeks; our hypothesised mechanism of change is reasoning; moderators include negative symptoms and working memory; and secondary outcomes include wellbeing, quality of life, and service use. The accessibility, usability and acceptability of the digital platform will be assessed. DISCUSSION: SlowMo has been developed as the first blended digital therapy to target fears of harm from others through an inclusive design approach. In addition to testing its efficacy, this trial will add to our understanding of psychological mechanisms in paranoia. The study will examine the usability and adherence of a novel digital therapy, including an app for self-management, in a large sample of people affected by severe mental health difficulties. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN32448671 . Registered prospectively on 30 January 2017. Date assigned 2 February 2017.

  • The effects of cannabidiol on persecutory ideation and anxiety in a high trait paranoid group.

    20 December 2017

    BACKGROUND: Previous studies have suggested that cannabidiol has anxiolytic and antipsychotic properties, raising hopes that cannabidiol will translate to the psychiatric clinic. Cannabidiol may be particularly useful for anxiety and paranoia in those at-risk of major mental illness. METHODS: Immersion in a controlled 3D virtual-reality scenario was used to assay persecutory ideation and anxiety in a sample of non-clinical volunteers ( n=32) pre-selected for high paranoid traits. Participants were randomised to receive oral cannabidiol (600 mg) or placebo 130 min prior to entering virtual-reality. Well-validated rating scales were used to assay persecutory thinking and anxiety. Salivary cortisol concentration, heart rate and blood pressure were measured over the course of the experimental session. RESULTS: Immersion in the virtual-reality session elicited anxiety as indexed by the Beck's anxiety inventory ( p<0.005), and increased cortisol concentration ( p=0.05), heart rate ( p<0.05) and systolic blood pressure ( p<0.05). However, cannabidiol had no impact upon any of these effects, except for a strong trend to increase anxiety ( p=0.09). Cannabidiol had no effect on persecutory ideation as assayed by the Community Assessment of Psychic Experiences questionnaire or the State Social Paranoia Scale. CONCLUSIONS: In contrast to previous studies, there was no evidence of any benefits of cannabidiol on anxiety or persecutory ideation in healthy volunteers with high trait paranoia. However, a larger sample will be required for a definitive study.

  • Blood Vessel Flow Studies

    26 August 2016

  • Blood Pressure

    26 August 2016

  • Cognitive testing

    26 August 2016

  • CCRF

    26 August 2016

  • Support

    18 October 2016

    Link to the FMRIB-OHBA intranet for information and documents relating to the building, scanning, recording and computing.

  • Published Paper: Science Translational Medicine

    27 April 2017

    "Ipsilesional anodal tDCS enhances the functional benefits of rehabilitation in patients after stroke" - Allman, Amadi et al. 2016

  • Published Paper: eLife

    27 April 2017

    "Perceptually relevant remapping of human somatotopy in 24 hours" - Kolasinski et al. 2016

  • Kadoorie Centre Critical Care Research Blog: November 2016

    11 January 2017

    Marco Pimentel is the Post-Doctoral Research Assistant working on the HAVEN project. He studied biomedical engineering at the New University of Lisbon, Portugal, and joined the Oxford Centre for Doctoral training in Healthcare Innovation in 2010. He completed his DPhil in Engineering in 2015 for which he focused on multivariate time-series modelling using Gaussian processes for detecting deterioration in vital-sign data acquired from post-operative patients. He has been working with the Critical Care Research Group since 2014 and his talk to the group was an achievement that delivered a full explanation of using patient and hospital data for research purposes without using maths or equations!

  • Charlie awarded NDCN Outreach Funding

    16 January 2017

    £500 awarded for the Centre for the Creative Brain at St Edmund Hall