Digital phenotyping: Towards replicable findings with comprehensive assessments and integrative models in bipolar disorders

Background: Digital phenotyping promises to unobtrusively obtaining a continuous and objective input of symptomatology from patients\u27 daily lives. The prime example are bipolar disorders, as smartphone parameters directly reflect bipolar symptomatology. Empirical studies, however, have yielded inconsistent findings. We believe that three main shortcomings have to be addressed to fully leverage the potential of digital phenotyping: short assessment periods, rare outcome assessments, and an extreme fragmentation of parameters without an integrative analytical strategy. Methods: To demonstrate how to overcome these shortcomings, we conducted frequent (biweekly) dimensional and categorical expert ratings and daily self-ratings over an extensive assessment period (12 months) in 29 patients with bipolar disorder. Digital phenotypes were monitored continuously. As an integrative analytical strategy, we used structural equation modelling to build latent psychopathological outcomes (mania, depression) and latent digital phenotype predictors (sleep, activity, communicativeness). Outcomes: Combining gold-standard categorical expert ratings with dimensional self and expert ratings resulted in two latent outcomes (mania and depression) with statistically meaningful factor loadings that dynamically varied over 299 days. Latent digital phenotypes of sleep and activity were associated with same-day latent manic psychopathology, suggesting that psychopathological alterations in bipolar disorders relate to domains (latent variables of sleep and activity) and not only to specific behaviors (such as the number of declined incoming calls). The identification of latent psychopathological outcomes that dimensionally vary on a daily basis will enable to empirically determine which combination of digital phenotypes at which days prior to an upcoming episode are viable as digital prodromal predictors. (DIPF/Orig.

Digital phenotyping: towards replicable findings with comprehensive assessments and integrative models in bipolar disorders

Background: Digital phenotyping promises to unobtrusively obtaining a continuous and objective input of symptomatology from patients’ daily lives. The prime example are bipolar disorders, as smartphone parameters directly reflect bipolar symptomatology. Empirical studies, however, have yielded inconsistent findings. We believe that three main shortcomings have to be addressed to fully leverage the potential of digital phenotyping: short assessment periods, rare outcome assessments, and an extreme fragmentation of parameters without an integrative analytical strategy. Methods: To demonstrate how to overcome these shortcomings, we conducted frequent (biweekly) dimensional and categorical expert ratings and daily self-ratings over an extensive assessment period (12 months) in 29 patients with bipolar disorder. Digital phenotypes were monitored continuously. As an integrative analytical strategy, we used structural equation modelling to build latent psychopathological outcomes (mania, depression) and latent digital phenotype predictors (sleep, activity, communicativeness). Outcomes: Combining gold-standard categorical expert ratings with dimensional self and expert ratings resulted in two latent outcomes (mania and depression) with statistically meaningful factor loadings that dynamically varied over 299 days. Latent digital phenotypes of sleep and activity were associated with same-day latent manic psychopathology, suggesting that psychopathological alterations in bipolar disorders relate to domains (latent variables of sleep and activity) and not only to specific behaviors (such as the number of declined incoming calls). The identification of latent psychopathological outcomes that dimensionally vary on a daily basis will enable to empirically determine which combination of digital phenotypes at which days prior to an upcoming episode are viable as digital prodromal predictors

Aims and structure of the German Research Consortium BipoLife for the study of bipolar disorder

Background: Bipolar disorder is a severe and heterogeneous mental disorder. Despite great advances in neuroscience over the past decades, the precise causative mechanisms at the transmitter, cellular or network level have so far not been unraveled. As a result, individual treatment decisions cannot be tailor-made and the uncertain prognosis is based on clinical characteristics alone. Although a subpopulation of patients have an excellent response to pharmacological monotherapy, other subpopulations have been less well served by the medical system and therefore require more focused attention. In particular individuals at high risk of bipolar disorder, young patients in the early stages of bipolar disorder, patients with an unstable highly relapsing course and patients with acute suicidal ideation have been identified as those in need. Structure: A research consortium of ten universities across Germany has therefore implemented a 4 year research agenda including three randomized controlled trials, one epidemiological trial and one cross-sectional trial to address these areas of unmet needs. The topics under investigation will be the improvement of early recognition, specific psychotherapy, and smartphones as an aid for early episode detection and biomarkers of lithium response. A subset of patients will be investigated utilizing neuroimaging (fMRI), neurophysiology (EEG), and biomaterials (genomics, transcriptomics). Conclusions: This article aims to outline the rationale, design, and methods of these individual studies

Aims and structure of the German Research Consortium BipoLife for the study of bipolar disorder

Background: Bipolar disorder is a severe and heterogeneous mental disorder. Despite great advances in neuroscience over the past decades, the precise causative mechanisms at the transmitter, cellular or network level have so far not been unraveled. As a result, individual treatment decisions cannot be tailor-made and the uncertain prognosis is based on clinical characteristics alone. Although a subpopulation of patients have an excellent response to pharmacological monotherapy, other subpopulations have been less well served by the medical system and therefore require more focused attention. In particular individuals at high risk of bipolar disorder, young patients in the early stages of bipolar disorder, patients with an unstable highly relapsing course and patients with acute suicidal ideation have been identified as those in need. Structure: A research consortium of ten universities across Germany has therefore implemented a 4 year research agenda including three randomized controlled trials, one epidemiological trial and one cross-sectional trial to address these areas of unmet needs. The topics under investigation will be the improvement of early recognition, specific psychotherapy, and smartphones as an aid for early episode detection and biomarkers of lithium response. A subset of patients will be investigated utilizing neuroimaging (fMRI), neurophysiology (EEG), and biomaterials (genomics, transcriptomics). Conclusions: This article aims to outline the rationale, design, and methods of these individual studies

Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

Corrigendum to "Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action [European Neuropsychopharmacology (2020) 36, 121-136]"

The authors regret that there was an error in the author list, this should appear as above. The authors apologise for any inconvenience caused