Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative
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 ben...
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| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2019-09-01
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| Series: | International Journal of Bipolar Disorders |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40345-019-0156-x |
| _version_ | 1818148949994766336 |
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| author | Jan Scott Diego Hidalgo-Mazzei Rebecca Strawbridge Allan Young Matthieu Resche-Rigon Bruno Etain Ole A. Andreassen Michael Bauer Djamila Bennabi Andrew M. Blamire Fawzi Boumezbeur Paolo Brambilla Nadia Cattane Annamaria Cattaneo Marie Chupin Klara Coello Yann Cointepas Francesc Colom David A. Cousins Caroline Dubertret Edouard Duchesnay Adele Ferro Aitana Garcia-Estela Jose Goikolea Antoine Grigis Emmanuel Haffen Margrethe C. Høegh Petter Jakobsen Janos L. Kalman Lars V. Kessing Farah Klohn-Saghatolislam Trine V. Lagerberg Mikael Landén Ute Lewitzka Ashley Lutticke Nicolas Mazer Monica Mazzelli Cristina Mora Thorsten Muller Estanislao Mur-Mila Ketil Joachim Oedegaard Leif Oltedal Erik Pålsson Dimitri Papadopoulos Orfanos Sergi Papiol Victor Perez-Sola Andreas Reif Philipp Ritter Roberto Rossi Thomas Schulze Fanny Senner Fiona E. Smith Letizia Squarcina Nils Eiel Steen Pete E. Thelwall Cristina Varo Eduard Vieta Maj Vinberg Michele Wessa Lars T. Westlye Frank Bellivier |
| author_facet | Jan Scott Diego Hidalgo-Mazzei Rebecca Strawbridge Allan Young Matthieu Resche-Rigon Bruno Etain Ole A. Andreassen Michael Bauer Djamila Bennabi Andrew M. Blamire Fawzi Boumezbeur Paolo Brambilla Nadia Cattane Annamaria Cattaneo Marie Chupin Klara Coello Yann Cointepas Francesc Colom David A. Cousins Caroline Dubertret Edouard Duchesnay Adele Ferro Aitana Garcia-Estela Jose Goikolea Antoine Grigis Emmanuel Haffen Margrethe C. Høegh Petter Jakobsen Janos L. Kalman Lars V. Kessing Farah Klohn-Saghatolislam Trine V. Lagerberg Mikael Landén Ute Lewitzka Ashley Lutticke Nicolas Mazer Monica Mazzelli Cristina Mora Thorsten Muller Estanislao Mur-Mila Ketil Joachim Oedegaard Leif Oltedal Erik Pålsson Dimitri Papadopoulos Orfanos Sergi Papiol Victor Perez-Sola Andreas Reif Philipp Ritter Roberto Rossi Thomas Schulze Fanny Senner Fiona E. Smith Letizia Squarcina Nils Eiel Steen Pete E. Thelwall Cristina Varo Eduard Vieta Maj Vinberg Michele Wessa Lars T. Westlye Frank Bellivier |
| author_sort | Jan Scott |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T12:59:16Z |
| format | Article |
| id | doaj.art-57ee4627676f46439dd606349ebeed81 |
| institution | Directory Open Access Journal |
| issn | 2194-7511 |
| language | English |
| last_indexed | 2024-12-11T12:59:16Z |
| publishDate | 2019-09-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | International Journal of Bipolar Disorders |
| spelling | doaj.art-57ee4627676f46439dd606349ebeed812022-12-22T01:06:29ZengSpringerOpenInternational Journal of Bipolar Disorders2194-75112019-09-017111010.1186/s40345-019-0156-xProspective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiativeJan Scott0Diego Hidalgo-Mazzei1Rebecca Strawbridge2Allan Young3Matthieu Resche-Rigon4Bruno Etain5Ole A. Andreassen6Michael Bauer7Djamila Bennabi8Andrew M. Blamire9Fawzi Boumezbeur10Paolo Brambilla11Nadia Cattane12Annamaria Cattaneo13Marie Chupin14Klara Coello15Yann Cointepas16Francesc Colom17David A. Cousins18Caroline Dubertret19Edouard Duchesnay20Adele Ferro21Aitana Garcia-Estela22Jose Goikolea23Antoine Grigis24Emmanuel Haffen25Margrethe C. Høegh26Petter Jakobsen27Janos L. Kalman28Lars V. Kessing29Farah Klohn-Saghatolislam30Trine V. Lagerberg31Mikael Landén32Ute Lewitzka33Ashley Lutticke34Nicolas Mazer35Monica Mazzelli36Cristina Mora37Thorsten Muller38Estanislao Mur-Mila39Ketil Joachim Oedegaard40Leif Oltedal41Erik Pålsson42Dimitri Papadopoulos Orfanos43Sergi Papiol44Victor Perez-Sola45Andreas Reif46Philipp Ritter47Roberto Rossi48Thomas Schulze49Fanny Senner50Fiona E. Smith51Letizia Squarcina52Nils Eiel Steen53Pete E. Thelwall54Cristina Varo55Eduard Vieta56Maj Vinberg57Michele Wessa58Lars T. Westlye59Frank Bellivier60Institute of Neuroscience, Newcastle UniversityBipolar and Depressive Disorders Unit, Department of Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, University of Barcelona, IDIBAPS, CIBERSAMCentre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonCentre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College LondonUniversité Paris DiderotUniversité Paris DiderotNORMENT Centre, Division of Mental Health and Addiction, Oslo University HospitalDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität DresdenDepartment of Clinical Psychiatry, Inserm CIC 1431, CHU BesançonInstitute of Cellular Medicine, Newcastle UniversityNeuroSpin, CEA, Université Paris-SaclayDepartment of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of MilanIRCCS Istituto Centro San Giovanni di Dio - FatebenefratelliIRCCS Istituto Centro San Giovanni di Dio - FatebenefratelliCATI Neuroimaging Platform, ICM, Pitié Salpétrière HospitalCopenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, University Hospital of CopenhagenNeuroSpin, CEA, Université Paris-SaclayMental Health Research Program, IMIM, Hospital del Mar, CIBERSAMInstitute of Neuroscience, Newcastle UniversityUniversité Paris DiderotNeuroSpin, CEA, Université Paris-SaclayDepartment of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of MilanMental Health Research Program, IMIM, Hospital del Mar, CIBERSAMBipolar and Depressive Disorders Unit, Department of Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, University of Barcelona, IDIBAPS, CIBERSAMNeuroSpin, CEA, Université Paris-SaclayDepartment of Clinical Psychiatry, Inserm CIC 1431, CHU BesançonNORMENT Centre, Division of Mental Health and Addiction, Oslo University HospitalNORMENT, Division of Psychiatry, Haukeland University HospitalInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU MunichCopenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, University Hospital of CopenhagenInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU MunichNORMENT Centre, Division of Mental Health and Addiction, Oslo University HospitalInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of GothenburgDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität DresdenInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU MunichAPHP; Psychiatry Department, University Hospital Louis MourierIRCCS Istituto Centro San Giovanni di Dio - FatebenefratelliIRCCS Istituto Centro San Giovanni di Dio - FatebenefratelliInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU MunichMental Health Research Program, IMIM, Hospital del Mar, CIBERSAMNORMENT, Division of Psychiatry, Haukeland University HospitalDepartment of Clinical Medicine, University of BergenInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of GothenburgNeuroSpin, CEA, Université Paris-SaclayInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU MunichMental Health Research Program, IMIM, Hospital del Mar, CIBERSAMDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital FrankfurtDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität DresdenUnit of Psychiatry, IRCCS Istituto Centro San Giovanni di Dio - FatebenefratelliInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU MunichInstitute of Cellular Medicine, Newcastle UniversityDepartment of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of MilanNORMENT Centre, Division of Mental Health and Addiction, Oslo University HospitalInstitute of Cellular Medicine, Newcastle UniversityBipolar and Depressive Disorders Unit, Department of Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, University of Barcelona, IDIBAPS, CIBERSAMBipolar and Depressive Disorders Unit, Department of Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, University of Barcelona, IDIBAPS, CIBERSAMCopenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, University Hospital of CopenhagenDepartment of Clinical Psychology and Neuropsychology, Institute for Psychology, Johannes Gutenberg-University MainzNORMENT Centre, Division of Mental Health and Addiction, Oslo University HospitalUniversité Paris DiderotAbstract 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.http://link.springer.com/article/10.1186/s40345-019-0156-xBipolarPrecisionPersonalizationLithiumResponsePhenotype |
| spellingShingle | Jan Scott Diego Hidalgo-Mazzei Rebecca Strawbridge Allan Young Matthieu Resche-Rigon Bruno Etain Ole A. Andreassen Michael Bauer Djamila Bennabi Andrew M. Blamire Fawzi Boumezbeur Paolo Brambilla Nadia Cattane Annamaria Cattaneo Marie Chupin Klara Coello Yann Cointepas Francesc Colom David A. Cousins Caroline Dubertret Edouard Duchesnay Adele Ferro Aitana Garcia-Estela Jose Goikolea Antoine Grigis Emmanuel Haffen Margrethe C. Høegh Petter Jakobsen Janos L. Kalman Lars V. Kessing Farah Klohn-Saghatolislam Trine V. Lagerberg Mikael Landén Ute Lewitzka Ashley Lutticke Nicolas Mazer Monica Mazzelli Cristina Mora Thorsten Muller Estanislao Mur-Mila Ketil Joachim Oedegaard Leif Oltedal Erik Pålsson Dimitri Papadopoulos Orfanos Sergi Papiol Victor Perez-Sola Andreas Reif Philipp Ritter Roberto Rossi Thomas Schulze Fanny Senner Fiona E. Smith Letizia Squarcina Nils Eiel Steen Pete E. Thelwall Cristina Varo Eduard Vieta Maj Vinberg Michele Wessa Lars T. Westlye Frank Bellivier Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative International Journal of Bipolar Disorders Bipolar Precision Personalization Lithium Response Phenotype |
| title | Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative |
| title_full | Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative |
| title_fullStr | Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative |
| title_full_unstemmed | Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative |
| title_short | Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative |
| title_sort | prospective cohort study of early biosignatures of response to lithium in bipolar i disorders overview of the h2020 funded r link initiative |
| topic | Bipolar Precision Personalization Lithium Response Phenotype |
| url | http://link.springer.com/article/10.1186/s40345-019-0156-x |
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