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      • Record: found
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      The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS): study protocol for a randomised controlled, experimental medicine study

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          Abstract

          Background

          The discovery that voltage-gated calcium channel genes such as CACNA1C are part of the aetiology of psychiatric disorders has rekindled interest in the therapeutic potential of L-type calcium channel (LTCC) antagonists. These drugs, licensed to treat hypertension and angina, have previously been used in bipolar disorder, but without clear results. Neither is much known about the broader effects of these drugs on the brain and behaviour.

          Methods

          The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS) is a high-intensity randomised, double-blind, placebo-controlled experimental medicine study on the effect of the LTCC antagonist nicardipine in healthy young adults with mood instability. An array of cognitive, psychiatric, circadian, physiological, biochemical and neuroimaging (functional magnetic resonance imaging and magnetoencephalography) parameters are measured during a 4-week period, with randomisation to drug or placebo on day 14. We are interested in whether nicardipine affects the stability of these measures, as well as its overall effects. Participants are genotyped for the CACNA1C risk polymorphism rs1006737.

          Discussion

          The results will clarify the potential of LTCC antagonists for repurposing or modification for use in psychiatric disorders in which cognition, mood and sleep are affected.

          Trial registration

          ISRCTN, ISRCTN33631053. Retrospectively registered on 8 June 2018 (applied 17 May 2018).

          Electronic supplementary material

          The online version of this article (10.1186/s13063-019-3175-0) contains supplementary material, which is available to authorized users.

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          Most cited references54

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          Contextual cueing: implicit learning and memory of visual context guides spatial attention.

          M. Chun, Y. JIANG (1998)
          Global context plays an important, but poorly understood, role in visual tasks. This study demonstrates that a robust memory for visual context exists to guide spatial attention. Global context was operationalized as the spatial layout of objects in visual search displays. Half of the configurations were repeated across blocks throughout the entire session, and targets appeared within consistent locations in these arrays. Targets appearing in learned configurations were detected more quickly. This newly discovered form of search facilitation is termed contextual cueing. Contextual cueing is driven by incidentally learned associations between spatial configurations (context) and target locations. This benefit was obtained despite chance performance for recognizing the configurations, suggesting that the memory for context was implicit. The results show how implicit learning and memory of visual context can guide spatial attention towards task-relevant aspects of a scene.
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            A theory of visual attention.

            Claus Bundesen (1990)
            A unified theory of visual recognition and attentional selection is developed by integrating the biased-choice model for single-stimulus recognition (Luce, 1963; Shepard, 1957) with a choice model for selection from multielement displays (Bundesen, Pedersen, & Larsen, 1984) in a race model framework. Mathematically, the theory is tractable, and it specifies the computations necessary for selection. The theory is applied to extant findings from a broad range of experimental paradigms. The findings include effects of object integrality in selective report, number and spatial position of targets in divided-attention paradigms, selection criterion and number of distracters in focused-attention paradigms, delay of selection cue in partial report, and consistent practice in search. On the whole, the quantitative fits are encouraging.
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              Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire.

              R Hirschfeld, J. Williams, R L Spitzer … (2000)
              Bipolar spectrum disorders, which include bipolar I, bipolar II, and bipolar disorder not otherwise specified, frequently go unrecognized, undiagnosed, and untreated. This report describes the validation of a new brief self-report screening instrument for bipolar spectrum disorders called the Mood Disorder Questionnaire. A total of 198 patients attending five outpatient clinics that primarily treat patients with mood disorders completed the Mood Disorder Questionnaire. A research professional, blind to the Mood Disorder Questionnaire results, conducted a telephone research diagnostic interview by means of the bipolar module of the Structured Clinical Interview for DSM-IV. A Mood Disorder Questionnaire screening score of 7 or more items yielded good sensitivity (0.73) and very good specificity (0.90). The Mood Disorder Questionnaire is a useful screening instrument for bipolar spectrum disorder in a psychiatric outpatient population.
              Article 0 comments Cited 279 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Lauren Z. Atkinson: lauren.atkinson@psych.ox.ac.uk
                Lucy Colbourne: lucy.colbourne@gtc.ox.ac.uk
                Catherine H. Harmer: catherine.harmer@psych.ox.ac.uk
                Anna C. Nobre: kia.nobre@psy.ox.ac.uk
                Jennifer Rendell: jennifer.rendell@psych.ox.ac.uk
                Helen Jones: helen.jones@oxfordhealth.nhs.uk
                Christopher Hinds: chris.hinds@bdi.ox.ac.uk
                Arne Mould: arne.mould@psych.ox.ac.uk
                Elizabeth M. Tunbridge: elizabeth.tunbridge@psych.ox.ac.uk
                Andrea Cipriani: andrea.cipriani@psych.ox.ac.uk
                John R. Geddes: john.geddes@psych.ox.ac.uk
                Kate E. A. Saunders: kate.saunders@psych.ox.ac.uk
                Paul J. Harrison:
                ORCID: http://orcid.org/0000-0002-6719-1126
                paul.harrison@psych.ox.ac.uk
                Journal
                Journal ID (nlm-ta): Trials
                Journal ID (iso-abbrev): Trials
                Title: Trials
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1745-6215
                Publication date (Electronic): 12 February 2019
                Publication date PMC-release: 12 February 2019
                Publication date Collection: 2019
                Volume: 20
                Electronic Location Identifier: 120
                Affiliations
                [1 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Department of Psychiatry, , University of Oxford, Warneford Hospital, ; Oxford, OX3 7JX UK
                [2 ]ISNI 0000 0004 0641 5119, GRID grid.416938.1, Oxford Health Foundation NHS Trust, , Warneford Hospital, ; Oxford, UK
                [3 ]ISNI 0000 0004 0641 5119, GRID grid.416938.1, Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, , Warneford Hospital, ; Oxford, UK
                [4 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Department of Experimental Psychology, , University of Oxford, New Radcliffe House, ; Oxford, UK
                [5 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Big Data Institute, University of Oxford, ; Old Road Campus, Oxford, UK
                Author information
                http://orcid.org/0000-0002-6719-1126
                Article
                Publisher ID: 3175
                DOI: 10.1186/s13063-019-3175-0
                PMC ID: 6373140
                PubMed ID: 30755265
                SO-VID: 0f8d7314-6120-4296-a991-a37c88fc69e3
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 11 July 2018
                Date accepted : 2 January 2019
                Funding
                Funded by: Wellcome Trust
                Award ID: 102616/Z
                Award ID: 098461/Z
                Award ID: 102176/Z
                Award Recipient :
                Funded by: National Institute for Health Research
                Award ID: BRC-1215-20005
                Categories
                Subject: Study Protocol
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Medicine
                Keywords: bipolar disorder,calcium blockers,calcium channel antagonists,depression,functional magnetic resonance imaging,magnetoencephalography,mood instability,sleep,working memory
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: bipolar disorder, calcium blockers, calcium channel antagonists, depression, functional magnetic resonance imaging, magnetoencephalography, mood instability, sleep, working memory

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