An evidence map of actigraphy studies exploring longitudinal associations between rest-activity rhythms and course and outcome of bipolar disorders

Background: Evidence mapping is a structured approach used to synthesize the state-of-the-art in an emerging field of research when systematic reviews or meta-analyses are deemed inappropriate. We employed this strategy to summarise knowledge regarding longitudinal ecological monitoring of rest-activity rhythms (RAR) and disease modifiers, course of illness, treatment response or outcome in bipolar disorders (BD). Structure: We had two key aims: (1) to determine the number and type of actigraphy studies of in BD that explored data regarding: outcome over time (e.g. relapse/recurrence according to polarity, or recovery/remission), treatment response or illness trajectories and (2) to examine the range of actigraphy metrics that can be used to estimate disruptions of RAR and describe which individual circadian rhythm or sleep-wake cycle parameters are most consistently associated with outcome over time in BD. The mapping process incorporated four steps: clarifying the project focus, describing boundaries and 'coordinates' for mapping, searching the literature and producing a brief synopsis with summary charts of the key outputs. Twenty-seven independent studies (reported in 29 publications) were eligible for inclusion in the map. Most were small-scale, with the median sample size being 15 per study and median duration of actigraphy being about 7 days (range 1-210). Interestingly, 17 studies comprised wholly or partly of inpatients (63%). The available evidence indicated that a discrete number of RAR metrics are more consistently associated with transition between different phases of BD and/or may be predictive of longitudinal course of illness or treatment response. The metrics that show the most frequent associations represent markers of the amount, timing, or variability of RAR rather than the sleep quality metrics that are frequently targeted in contemporary studies of BD. Conclusions: Despite 50 years of research, use of actigraphy to assess RAR in longitudinal studies and examination of these metrics and treatment response, course and outcome of BD is under-investigated. This is in marked contrast to the extensive literature on case-control or cross-sectional studies of actigraphy, especially typical sleep analysis metrics in BD. However, given the encouraging findings on putative RAR markers, we recommend increased study of putative circadian phenotypes of BD. FB is the Principal Investigator and all the authors are investigators on the R-LiNK (Response to Lithium Network) project. This project has received funding from the European Union Horizon 2020 research and innovation program ((EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907). BE received funding from: Institut National de la Santé et de la Recherche Médicale (INSERM – Research Protocol C0829), Assistance Publique des Hôpitaux de Paris (APHP – Research Protocol GAN12). FC received funding from: Spanish Ministry of Economy and Competitiveness, through a FIS (PI15/00588; PI19/00009), and the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya, Government of Catalonia (2017_SGR_134). AY received funding from: National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.