{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:36:14Z","timestamp":1790386574851,"version":"4.1.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T00:00:00Z","timestamp":1569369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T00:00:00Z","timestamp":1569369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"H2020 Research and Innovation Program","award":["754907"],"award-info":[{"award-number":["754907"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Bipolar Disord"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Structure<\/jats:title>\n                <jats:p>The H2020-funded Response to Lithium Network (R-LiNK; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.r-link.eu.com\/\">http:\/\/www.r-link.eu.com\/<\/jats:ext-link>) 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\u00a0months and an independent panel will assess and classify each participants\u2019 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.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              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JS is a Visiting Professor at Diderot University, Paris and an Honorary Professor at Kings College, London. AY declares paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, and Janssen. He is a paid consultant to Johnson & Johnson, is lead Investigator for Embolden Study (AstraZeneca), BCI Neuroplasticity study and a pharma sponsored Aripiprazole in Mania study. His institution has received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck, Wyeth, and Janssen. D.A. Cousins, F.E. Smith, P.E. Thelwall and A.M. Blamire are conducting the Bipolar Lithium Imaging and Spectroscopy Study (BLISS; Medical Research Council Clinician Scientist Award to DAC\u2014BH135495), a cross sectional evaluation of the effects of lithium on brain structure and composition with respect to response. This study led to the development of the\u00a0<sup>7<\/sup>Li-MRI technique used in the R-LiNK study; the authors report no competing interests with respect to this and have no other declarations. Competing interests and declarations for other co-authors available upon request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20"}}