Abstract

Background

Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need.

Structure

The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants’ response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence.

Conclusions

The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.

Details

Title
Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative
Author
Scott, Jan 1 ; Hidalgo-Mazzei, Diego 2 ; Strawbridge, Rebecca 3 ; Young, Allan 3 ; Resche-Rigon, Matthieu 4 ; Bruno Etain 5 ; Andreassen, Ole A 6 ; Bauer, Michael 7 ; Bennabi, Djamila 8 ; Blamire, Andrew M 9 ; Boumezbeur, Fawzi 10 ; Brambilla, Paolo 11 ; Cattane, Nadia 12 ; Cattaneo, Annamaria 12 ; Chupin, Marie 13 ; Coello, Klara 14 ; Cointepas, Yann 15 ; Colom, Francesc 16 ; Cousins, David A 17 ; Dubertret, Caroline 18 ; Duchesnay, Edouard 10 ; Ferro, Adele 19 ; Garcia-Estela, Aitana 16 ; Goikolea, Jose 2 ; Grigis, Antoine 10 ; Haffen, Emmanuel 8 ; Høegh, Margrethe C 6 ; Jakobsen, Petter 20 ; Kalman, Janos L 21 ; Kessing, Lars V 14 ; Farah Klohn-Saghatolislam 22 ; Lagerberg, Trine V 23 ; Landén, Mikael 24 ; Lewitzka, Ute 7 ; Lutticke, Ashley 22 ; Mazer, Nicolas 25 ; Mazzelli, Monica 12 ; Mora, Cristina 12 ; Muller, Thorsten 26 ; Mur-Mila, Estanislao 16 ; Oedegaard, Ketil Joachim 20 ; Oltedal, Leif 27 ; Pålsson, Erik 24 ; Dimitri Papadopoulos Orfanos 10 ; Papiol, Sergi 22 ; Perez-Sola, Victor 16 ; Reif, Andreas 28 ; Ritter, Philipp 7 ; Rossi, Roberto 29 ; Schulze, Thomas 26 ; Senner, Fanny 22 ; Smith, Fiona E 9 ; Squarcina, Letizia 19 ; Steen, Nils Eiel 6 ; Thelwall, Pete E 9 ; Varo, Cristina 2 ; Vieta, Eduard 2 ; Vinberg, Maj 14 ; Wessa, Michele 30 ; Westlye, Lars T 31 ; Bellivier, Frank 5   VIAFID ORCID Logo 

1  Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK; Université Paris Diderot, Paris, France 
2  Bipolar and Depressive Disorders Unit, Department of Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain 
3  Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK 
4  Université Paris Diderot, Paris, France; Service de Biostatistique et Information Médicale, Hôpital Saint-Louis, AP-HP, Paris, France; Inserm, UMR 1153, Equipe ECSTRA, Paris, France 
5  Université Paris Diderot, Paris, France; Département de Psychiatrie et de Médecine Addictologique, AP-HP, GH Saint-Louis – Lariboisière – F. Widal, Paris, France; Inserm, U1144, Team 1, Paris, France 
6  NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway 
7  Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany 
8  Department of Clinical Psychiatry, Inserm CIC 1431, CHU Besançon, Besançon, France; Laboratoire de Neurosciences, Université Bourgogne Franche-Comté, Besançon, France 
9  Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK 
10  NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France 
11  Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; Department of Psychiatry and Behavioural Neurosciences, University of Texas at Houston, Houston, TX, USA 
12  IRCCS Istituto Centro San Giovanni di Dio - Fatebenefratelli, Brescia, Italy 
13  CATI Neuroimaging Platform, ICM, Pitié Salpétrière Hospital, Paris, France; Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; Inserm, U1127, Paris, France; CNRS, UMR 7225, Paris, France; Sorbonne Université, Paris, France 
14  Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, University Hospital of Copenhagen, Copenhagen, Denmark 
15  NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France; CATI Neuroimaging Platform, ICM, Pitié Salpétrière Hospital, Paris, France 
16  Mental Health Research Program, IMIM, Hospital del Mar, CIBERSAM, Barcelona, Catalonia, Spain 
17  Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK 
18  Université Paris Diderot, Paris, France; APHP; Psychiatry Department, University Hospital Louis Mourier, Colombes, France; INSERM U894, Institute of Psychiatry and Neurosciences of Paris, Paris, France 
19  Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy 
20  NORMENT, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway 
21  Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany 
22  Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany 
23  NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway 
24  Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 
25  APHP; Psychiatry Department, University Hospital Louis Mourier, Colombes, France; INSERM U894, Institute of Psychiatry and Neurosciences of Paris, Paris, France 
26  Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany 
27  Department of Clinical Medicine, University of Bergen, Bergen, Norway; Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway 
28  Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany 
29  Unit of Psychiatry, IRCCS Istituto Centro San Giovanni di Dio - Fatebenefratelli, Brescia, Italy 
30  Department of Clinical Psychology and Neuropsychology, Institute for Psychology, Johannes Gutenberg-University Mainz, Mainz, Germany 
31  NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway 
Pages
1-10
Publication year
2019
Publication date
Sep 2019
Publisher
Springer Nature B.V.
e-ISSN
21947511
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s40345-019-0156-x
ProQuest document ID
2296519819
Copyright
International Journal of Bipolar Disorders is a copyright of Springer, (2019). All Rights Reserved., © 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.