Abstract
Background: Bipolar disorder (BD) is defined by complex, poorly understood mood dynamics. Our current inability to predict significant changes in mood, particularly episode relapses, is one of the most challenging features of BD for patients and clinicians. Research into sleep and circadian rhythm disruption suggests that relapse risk may be measurable in 24-hour rest-activity rhythms (RAR) collected by actigraphy. This protocol describes a multi-study project with two synergistic aims - to develop an algorithm of relapse risk based on RAR data and to advance mechanistic understanding of sleep and circadian rhythm features of RARs.
Method: Three prospective studies will enrol adults living with BD I or II. Study 1 (Australia) will recruit a sample of N = 100 individuals with inter-episode BD who will participate in three contiguous 26-week monitoring epochs. Each epoch commences with 14 days of actigraphy, followed by follow-up interviews at 13 and 26 weeks. RAR predictors of time to first relapse will be explored using Cox’s survival analysis, Bayesian Network and Machine Learning analyses, and Hadaeghi’s Complex System model of BD. Study 2 (India) will recruit 25 individuals with BD and 25 matched healthy controls and replicate one of the 26-week epochs conducted in Study 1. Study 2 tests the replicability of models identified in Study 1 in a lower-middle-income country and investigates the association between amplitude of the RAR and amplitude of the diurnal rhythm in clock gene expression and associated metabolites. Study 3 (New Zealand) will collect actigraphy data from people experiencing a severe episode of BD depression (N = 30) or mania (N = 15), to model the prediction of treatment response and outcome of acute illness episodes.
Discussion: The 5-year Tipping Point project uses novel methods and analyses to develop clinically critical inferences about the short-term course of BD. If replicated in future independent samples, the risk forecasting algorithm to be identified here could be translated into practice.