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Forecasting the course of bipolar disorder using rest-activity rhythms: Protocol for a multi-study modelling project

2025· preprint· en· W4411410754 on OpenAlexaff
Sandipan Ray, Richard Porter, Fatemeh Hadaeghi, Denny Meyer, Sara Lapsley, Matthew Aaron Tennant, Bridgette Thwaites, Ly Nguyen, Hailey Tremain, Jan Scott

Bibliographic record

VenueWellcome Open Research · 2025
Typepreprint
Languageen
FieldPsychology
TopicMental Health Research Topics
Canadian institutionsUniversity of Victoria
FundersWellcome Trust
KeywordsActigraphyCircadian rhythmMoodBipolar disorderRhythmPsychologyChronobiologyCLOCKReplicateManiaPsychiatryCircadian clockMedicineInternal medicineNeuroscienceStatistics

Abstract

fetched live from OpenAlex

<ns5:p> 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 <ns5:italic>N</ns5:italic> = 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 ( <ns5:italic>N</ns5:italic> = 30) or mania ( <ns5:italic>N</ns5:italic> = 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. </ns5:p>

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How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.019
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Science and technology studies, Open science, Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Protocol · Consensus signal: Protocol
Teacher disagreement score0.872
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0190.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0040.009
Research integrity0.0010.004
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.821
GPT teacher head0.657
Teacher spread0.164 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designSimulation or modeling
Domainnot available
GenreProtocol

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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