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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.

BackgroundSIMPLe is an internet‐delivered self‐management mobile app for bipolar disorder (BD) designed to combine technology with evidence-based interventions and facilitate access to psychoeducational content. The SIMPLe app was launched to the real world to make it available worldwide within the context of BD treatment. ObjectiveThe main aims of this study are as follows: to describe app use, engagement, and retention rates based on server data; to identify patterns of user retention over the first 6-month follow-up of use; and to explore potential factors contributing to discontinuation of app use. MethodsThis was an observational ecological study in which we pooled available data from a real-world implementation of the SIMPLe app. Participation was open on the project website, and the data-collection sources were a web-based questionnaire on clinical data and treatment history administered at inclusion and at 6 months, subjective data gathered through continuous app use, and the use patterns captured by the app server. Characteristics and engagement of regular users, occasional users, and no users were compared using 2-tailed t tests or analysis of variance or their nonparametric equivalent. Survival analysis and risk functions were applied to regular users’ data to examine and compare use and user retention. In addition, a user evaluation analysis was performed based on satisfaction, perceived usefulness, and reasons to discontinue app use. ResultsWe included 503 participants with data collected between 2016 and 2018, of whom 77.5% (n=390) used the app. Among the app users, 44.4% (173/390) completed the follow-up assessment, and data from these participants were used in our analyses. Engagement declined gradually over the first 6 months of use. The probability of retention of the regular users after 1 month of app use was 67.4% (263/390; 95% CI 62.7%-72.4%). Age (P=.002), time passed since illness onset (P

Background: Bipolar Disorder (BD) and Borderline Personality Disorder (BPD) have clinically been evolving as separate disorders, though there is still debate on the nosological valence of both conditions, their interaction in terms of co-morbidity or disorder spectrum and their distinct pathophysiology.Objective: The objective of this review is to summarize evidence regarding clinical features, neuropsychological performance and neuroimaging findings from cross-diagnostic studies comparing BD and BPD, to further caracterize their complex interplay.Methods: Using PubMed, PsycINFO and TripDataBase, we conducted a systematic literature search based on PRISMA guidelines of studies published from January 1980 to September 2019 which directly compared BD and BPD.Results: A total of 28 studies comparing BD and BPD were included: 19 compared clinical features, 6 neuropsychological performance and three neuroimaging abnormalities. Depressive symptoms have an earlier onset in BPD than BD. BD patients present more mixed or manic symptoms, with BD-I differing from BPD in manic phases. BPD patients show more negative attitudes toward others and self, more conflictive interpersonal relationships, and more maladaptive regulation strategies in affective instability with separate pathways. Impulsivity seems more a trait in BPD rather than a state as in BD. Otherwise, BD and BPD overlap in depressive and anxious symptoms, dysphoria, various abnormal temperamental traits, suicidal ideation, and childhood trauma. Both disorders differ and share deficits in neuropsychological and neuroimaging findings.Conclusion: Clinical data provide evidence of overlapping features in both disorders, with most of those shared symptoms being more persistent and intense in BPD. Thus, categorical classifications should be compared to dimensional approaches in transdiagnostic studies investigating BPD features in BD regarding their respective explanatory power for individual trajectories.Systematic Review Registration: The search strategy was pre-registered in PROSPERO: CRD42018100268.