TY - JOUR

T1 - Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders

T2 - overview of the H2020-funded R-LiNK initiative

AU - Scott, Jan

AU - Hidalgo-Mazzei, Diego

AU - Strawbridge, Rebecca

AU - Young, Allan

AU - Resche-Rigon, Matthieu

AU - Etain, Bruno

AU - Andreassen, Ole A

AU - Bauer, Michael

AU - Bennabi, Djamila

AU - Blamire, Andrew M

AU - Boumezbeur, Fawzi

AU - Brambilla, Paolo

AU - Cattane, Nadia

AU - Cattaneo, Annamaria

AU - Chupin, Marie

AU - Coello, Klara

AU - Cointepas, Yann

AU - Colom, Francesc

AU - Cousins, David A

AU - Dubertret, Caroline

AU - Duchesnay, Edouard

AU - Ferro, Adele

AU - Garcia-Estela, Aitana

AU - Goikolea, Jose

AU - Grigis, Antoine

AU - Haffen, Emmanuel

AU - Høegh, Margrethe C

AU - Jakobsen, Petter

AU - Kalman, Janos L

AU - Kessing, Lars V

AU - Klohn-Saghatolislam, Farah

AU - Lagerberg, Trine V

AU - Landén, Mikael

AU - Lewitzka, Ute

AU - Lutticke, Ashley

AU - Mazer, Nicolas

AU - Mazzelli, Monica

AU - Mora, Cristina

AU - Muller, Thorsten

AU - Mur-Mila, Estanislao

AU - Oedegaard, Ketil Joachim

AU - Oltedal, Leif

AU - Pålsson, Erik

AU - Papadopoulos Orfanos, Dimitri

AU - Papiol, Sergi

AU - Perez-Sola, Victor

AU - Reif, Andreas

AU - Ritter, Philipp

AU - Rossi, Roberto

AU - Schulze, Thomas

AU - Senner, Fanny

AU - Smith, Fiona E

AU - Squarcina, Letizia

AU - Steen, Nils Eiel

AU - Thelwall, Pete E

AU - Varo, Cristina

AU - Vieta, Eduard

AU - Vinberg, Maj

AU - Wessa, Michele

AU - Westlye, Lars T

AU - Bellivier, Frank

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1186/s40345-019-0156-x

DO - 10.1186/s40345-019-0156-x

M3 - Review

C2 - 31552554

VL - 7

JO - International Journal of Bipolar Disorders

JF - International Journal of Bipolar Disorders

SN - 2194-7511

M1 - 20

ER -