Anticipating clinical transitions in bipolar disorder (BD) is essential for the development of clinically actionable predictions. Our aim was to determine what is the earliest indicator of the onset of depressive symptoms in BD. We hypothesized that changes in activity would be the earliest indicator of future depressive symptoms. The study was a prospective, observational, contactless study. Participants were 127 outpatients with a primary diagnosis of BD, followed up for 12.6 (5.7) [(mean (SD)] months. They wore a smart ring continuously, which monitored their daily activity and sleep parameters. Participants were also asked to complete weekly self-ratings using the Patient Health Questionnaire (PHQ-9) and Altman Self-Rating Mania Scale (ASRS) scales. Primary outcome measures were depressive symptom onset detection metrics (i.e., accuracy, sensitivity, and specificity); and detection delay (in days), compared between self-rating scales and wearable data. Depressive symptoms were labeled as two or more consecutive weeks of total PHQ-9 > 10, and data-driven symptom onsets were detected using time-frequency spectral derivative spike detection (TF-SD2). Our results showed that day-to-day variability in the number of steps anticipated the onset of depressive symptoms 7.0 (9.0) (median (IQR)) days before they occurred, significantly earlier than the early prediction window provided by deep sleep duration (median (IQR), 4.0 (5.0) days; p <.05). Taken together, our results demonstrate that changes in activity were the earliest indicator of depressive symptoms in participants with BD. Transition to dynamic representations of behavioral phenomena in psychiatry may facilitate episode forecasting and individualized preventive interventions.

Campbell Family Research Institute Centre for Addiction and Mental Health Toronto ON Canada

Department of MicroData Analytics Dalarna University Dalarna Sweden

Department of Psychiatry Dalhousie University Halifax NS Canada

Department of Psychiatry Temerty Faculty of Medicine University of Toronto Toronto ON Canada

National Institute of Mental Health Klecany Czech Republic

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Akiskal HS, Azorin JM, Hantouche EG. Proposed multidimensional structure of mania: beyond the euphoric-dysphoric dichotomy. J Affect Disord. 2003;73:7–18. PubMed

Alloy LB, Abramson LY, Walshaw PD, Cogswell A, Grandin LD, Hughes ME, Iacoviello BM, Whitehouse WG, Urosevic S, Nusslock R, Hogan ME. Behavioral approach system and behavioral Inhibition system sensitivities and bipolar spectrum disorders: prospective prediction of bipolar mood episodes. Bipolar Disord. 2008;10:310–22. PubMed

Altini M, Kinnunen H. The promise of sleep: A Multi-Sensor approach for accurate sleep stage detection using the Oura ring. Sensors. 2021;21:4302. PubMed PMC

Altman EG, Hedeker D, Peterson JL, Davis JM. The Altman Self-Rating mania scale. Biol Psychiatry. 1997;42:948–55. PubMed

Angst J, Gamma A, Bowden CL, Azorin JM, Perugi G, Vieta E, Young AH. Diagnostic criteria for bipolarity based on an international sample of 5,635 patients with DSM-IV major depressive episodes. Eur Arch Psychiatry Clin Neurosci. 2012;262:3–11. PubMed

Arndt S, Andreasen NC, Flaum M, Miller D, Nopoulos P. A longitudinal study of symptom dimensions in schizophrenia. Prediction and patterns of change. Arch Gen Psychiatry. 1995;52:352–60. PubMed

Bos EH, De Jonge P. Critical slowing down in depression is a great Idea that still needs empirical proof. Proc Natl Acad Sci U S A. 2014;111:E878. PubMed PMC

Bos FM, Schreuder MJ, George SV, Doornbos B, Bruggeman R, van der Krieke L, Haarman BCM, Wichers M, Snippe E. Anticipating manic and depressive transitions in patients with bipolar disorder using early warning signals. Int J Bipolar Disorders. 2022;10:12. PubMed PMC

Brys ADH, Stifft F, Van Heugten CM, Bossola M, Gambaro G, Lenaert B. mHealth-based experience sampling method to identify fatigue in the context of daily life in haemodialysis patients. Clin Kidney J. 2021;14:245–54. PubMed PMC

Bui Q, Kaufman KJ, Munsell EG, Lenze EJ, Lee JM, Mohr DC, Fong MW, Metts CL, Tomazin SE, Pham V, Wong AW. 2022. Smartphone assessment uncovers real-time relationships between depressed mood and daily functional behaviors after stroke. J Telemed Telecare, 1357633x221100061. PubMed PMC

Cheniaux E, Filgueiras A, Silva Rde A, Silveira LA, Nunes AL, Landeira-Fernandez J. Increased energy/activity, not mood changes, is the core feature of mania. J Affect Disord. 2014;152–154:256–61. PubMed

Cizek V. Discrete hilbert transform. IEEE Trans Audio Electroacoust. 1970;18:340–3.

Colominas MA, Schlotthauer G, Torres ME. Improved complete ensemble EMD: A suitable tool for biomedical signal processing. Biomed Signal Process Control. 2014;14:19–29.

Dablander F, Bury TM. Deep learning for tipping points: preprocessing matters. Proc Natl Acad Sci U S A. 2022;119:e2207720119. PubMed PMC

de Wild-Hartmann JA, Wichers M, van Bemmel AL, Derom C, Thiery E, Jacobs N, van Os J, Simons CJ. Day-to-day associations between subjective sleep and affect in regard to future depression in a female population-based sample. Br J Psychiatry. 2013;202:407–12. PubMed

de Zambotti M, Rosas L, Colrain IM, Baker FC. 2017. The sleep of the ring: comparison of the OURA sleep tracker against polysomnography. Behav Sleep Med, 1–15. PubMed PMC

Depp C, Torous J, Thompson W. 2016. Technology-Based early warning systems for bipolar disorder: A conceptual framework. JMIR Ment Health 3, e42. PubMed PMC

Depp CA, Thompson WK, Frank E, Swartz HA. Prediction of near-term increases in suicidal ideation in recently depressed patients with bipolar II disorder using intensive longitudinal data. J Affect Disord. 2017;208:363–8. PubMed PMC

Depue RA, Slater JF, Wolfstetter-Kausch H, Klein D, Goplerud E, Farr D. A behavioral paradigm for identifying persons at risk for bipolar depressive disorder: a conceptual framework and five validation studies. J Abnorm Psychol. 1981;90:381–437. PubMed

Diagnostic. and Statistical manual of mental disorders, 5th ed. American Psychiatric Association, Arlington. VA. 2013

Ebner-Priemer UW, Trull TJ. Ecological momentary assessment of mood disorders and mood dysregulation. Psychol Assess. 2009;21:463–75. PubMed

Ebner-Priemer UW, Mühlbauer E, Neubauer AB, Hill H, Beier F, Santangelo PS, Ritter P, Kleindienst N, Bauer M, Schmiedek F, Severus E. Digital phenotyping: towards replicable findings with comprehensive assessments and integrative models in bipolar disorders. Int J Bipolar Disorders. 2020;8:35. PubMed PMC

Faurholt-Jepsen M, Frost M, Vinberg M, Christensen EM, Bardram JE, Kessing LV. Smartphone data as objective measures of bipolar disorder symptoms. Psychiatry Res. 2014;217:124–7. PubMed

Faurholt-Jepsen M, Vinberg M, Frost M, Christensen EM, Bardram JE, Kessing LV. Smartphone data as an electronic biomarker of illness activity in bipolar disorder. Bipolar Disord. 2015;17:715–28. PubMed

Faurholt-Jepsen M, Busk J, Thornorarinsdottir H, Frost M, Bardram JE, Vinberg M, Kessing LV. Objective smartphone data as a potential diagnostic marker of bipolar disorder. Aust N Z J Psychiatry. 2019;53:119–28. PubMed

First M, Williams J, Karg R, RL S. Structured clinical interview for DSM-5, research version (SCID-5). Arlington, VA: American Psychiatric Association; 2015.

Forster SD, Gauggel S, Loevenich R, Völzke V, Petershofer A, Zimmermann P, Privou C, Bonnert J, Mainz V. A microanalysis of mood and Self-Reported functionality in stroke patients using ecological momentary assessment. Front Neurol. 2022;13:854777. PubMed PMC

Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW, Rush AJ, Weissman MM. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991;48:851–5. PubMed

Franklin JC, Ribeiro JD, Fox KR, Bentley KH, Kleiman EM, Huang X, Musacchio KM, Jaroszewski AC, Chang BP, Nock MK. Risk factors for suicidal thoughts and behaviors: A meta-analysis of 50 years of research. Psychol Bull. 2017;143:187–232. PubMed

Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rössler A, Schultze-Lutter F, Keshavan M, Wood S, Ruhrmann S, Seidman LJ, Valmaggia L, Cannon T, Velthorst E, De Haan L, Cornblatt B, Bonoldi I, Birchwood M, McGlashan T, Carpenter W, McGorry P, Klosterkötter J, McGuire P, Yung A. The psychosis high-risk State: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013;70:107–20. PubMed PMC

Giurgiu M, Koch ED, Ottenbacher J, Plotnikoff RC, Ebner-Priemer UW, Reichert M. Sedentary behavior in everyday life relates negatively to mood: an ambulatory assessment study. Scand J Med Sci Sports. 2019;29:1340–51. PubMed

Halabi R, Mulsant BH, Alda M, DeShaw A, Hintze A, Husain MI, O’Donovan C, Patterson R, Ortiz A. Not missing at random: missing data are associated with clinical status and trajectories in an electronic monitoring longitudinal study of bipolar disorder. J Psychiatr Res. 2024;174:326–31. PubMed PMC

Hargreaves WA, Blacker KH. A dynamic approach to descriptive psychiatry. Patterns of symptom change in daily clinical ratings. Arch Gen Psychiatry. 1967;16:390–8. PubMed

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42:377–81. PubMed PMC

Hawley CJ, Gale TM, Sivakumaran T. Defining remission by cut off score on the MADRS: selecting the optimal value. J Affect Disord. 2002;72:177–84. PubMed

Hidalgo-Mazzei D, Reinares M, Mateu A, Nikolova VL, Bonnín CDM, Samalin L, García-Estela A, Pérez-Solá V, Young AH, Strejilevich S, Vieta E, Colom F. OpenSIMPLe: A real-world implementation feasibility study of a smartphone-based psychoeducation programme for bipolar disorder. J Affect Disord. 2018;241:436–45. PubMed

Kendler KS, Zachar P, Craver C. What kinds of things are psychiatric disorders? Psychol Med. 2011;41:1143–50. PubMed

Kramer I, Simons CJ, Wigman JT, Collip D, Jacobs N, Derom C, Thiery E, van Os J, Myin-Germeys I, Wichers M. Time-lagged moment-to-moment interplay between negative affect and paranoia: new insights in the affective pathway to psychosis. Schizophr Bull. 2014;40:278–86. PubMed PMC

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606–13. PubMed PMC

Kunkels YK, Riese H, Knapen SE, Riemersma-van der Lek RF, George SV, van Roon AM, Schoevers RA, Wichers M. Efficacy of early warning signals and spectral periodicity for predicting transitions in bipolar patients: an actigraphy study. Transl Psychiatry. 2021;11:350. PubMed PMC

Lenderking WR, Hu M, Tennen H, Cappelleri JC, Petrie CD, Rush AJ. Daily process methodology for measuring earlier antidepressant response. Contemp Clin Trials. 2008;29:867–77. PubMed

Levis B, Benedetti A, Thombs BD. Accuracy of patient health Questionnaire-9 (PHQ-9) for screening to detect major depression: individual participant data meta-analysis. BMJ. 2019;365:l1476. PubMed PMC

Machado-Vieira R, Luckenbaugh DA, Ballard ED, Henter ID, Tohen M, Suppes T, Zarate CA Jr. Increased activity or energy as a primary criterion for the diagnosis of bipolar mania in DSM-5: findings from the STEP-BD study. Am J Psychiatry. 2017;174:70–6. PubMed PMC

Merikangas KR, Swendsen J, Hickie IB, Cui L, Shou H, Merikangas AK, Zhang J, Lamers F, Crainiceanu C, Volkow ND, Zipunnikov V. Real-time mobile monitoring of the dynamic associations among motor activity, energy, mood, and sleep in adults with bipolar disorder. JAMA Psychiatry. 2019;76:190–8. PubMed PMC

Meyer N, Joyce DW, Karr C, de Vos M, Dijk DJ, Jacobson NC, MacCabe JH. The Temporal dynamics of sleep disturbance and psychopathology in psychosis: a digital sampling study. Psychol Med. 2022;52:2741–50. PubMed PMC

Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–9. PubMed

Moriarty AS, Meader N, Snell KI, Riley RD, Paton LW, Chew-Graham CA, Gilbody S, Churchill R, Phillips RS, Ali S, McMillan D. Prognostic models for predicting relapse or recurrence of major depressive disorder in adults. Cochrane Database Syst Rev. 2021;5:Cd013491. PubMed PMC

Naliboff BD, Schrepf AD, Stephens-Shields AJ, Clemens JQ, Pontari MA, Labus J, Taple BJ, Rodriguez LV, Strachan E, Griffith JW. Temporal relationships between pain, mood and urinary symptoms in urological chronic pelvic pain syndrome: A MAPP network study. J Urol. 2021;205:1698–703. PubMed PMC

Nelson B, McGorry PD, Wichers M, Wigman JTW, Hartmann JA. Moving from static to dynamic models of the onset of mental disorder: A review. JAMA Psychiatry. 2017;74:528–34. PubMed

Odgers CL, Mulvey EP, Skeem JL, Gardner W, Lidz CW, Schubert C. Capturing the ebb and flow of psychiatric symptoms with dynamical systems models. Am J Psychiatry. 2009;166:575–82. PubMed

Ong JL, Golkashani HA, Ghorbani S, Wong KF, Chee NIYN, Willoughby AR, Chee MWL. Selecting a sleep tracker from EEG-based, iteratively improved, low-cost multisensor, and actigraphy-only devices. Sleep Health. 2024;10:9–23. PubMed

Ortiz A, Bradler K, Garnham J, Slaney C, Alda M. Nonlinear dynamics of mood regulation in bipolar disorder. Bipolar Disord. 2015;17:139–49. PubMed

Ortiz A, Bradler K, Radu L, Alda M, Rusak B. Exponential state transition dynamics in the rest-activity architecture of patients with bipolar disorder. Bipolar Disord. 2016;18:116–23. PubMed

Ortiz A, Bradler K, Hintze A. Episode forecasting in bipolar disorder: is energy better than mood? Bipolar Disord. 2018;20:470–6. PubMed

Ortiz A, Bradler K, Mowete M, MacLean S, Garnham J, Slaney C, Mulsant BH, Alda M. The futility of long-term predictions in bipolar disorder: mood fluctuations are the result of deterministic chaotic processes. Int J Bipolar Disord. 2021;9:30. PubMed PMC

Ortiz A, Halabi R. Individualized prediction of acute symptom onset using actimetric sensor data. 2024. Patent (submitted).

Ortiz A, Hintze A, Burnett R, Gonzalez-Torres C, Unger S, Yang D, Miao J, Alda M, Mulsant BH. Identifying patient-specific behaviors to understand illness trajectories and predict relapses in bipolar disorder using passive sensing and deep anomaly detection: protocol for a contactless cohort study. BMC Psychiatry. 2022;22:288. PubMed PMC

Ortiz A, Park Y, Gonzalez-Torres C, Alda M, Blumberger DM, Burnett R, Husain MI, Sanches M, Mulsant BH. Predictors of adherence to electronic self-monitoring in patients with bipolar disorder: a contactless study using growth mixture models. Int J Bipolar Disord. 2023;11:18. PubMed PMC

Patapoff M, Ramsey M, Titone M, Kaufmann CN, Malhotra A, Ancoli-Israel S, Wing D, Lee E, Eyler LT. Temporal relationships of ecological momentary mood and actigraphy-based sleep measures in bipolar disorder. J Psychiatr Res. 2022;150:257–63. PubMed PMC

Robbins R, Weaver MD, Sullivan JP, Quan SF, Gilmore K, Shaw S, Benz A, Qadri S, Barger LK, Czeisler CA, Duffy JF. Accuracy of three commercial wearable devices for sleep tracking in healthy adults. Sensors. 2024;24:6532. PubMed PMC

Scott J, Murray G, Henry C, Morken G, Scott E, Angst J, Merikangas KR, Hickie IB. Activation in bipolar disorders: A systematic review. JAMA Psychiatry. 2017;74:189–96. PubMed

Stochl J, Fried EI, Fritz J, Croudace TJ, Russo DA, Knight C, Jones PB, Perez J. On dimensionality, measurement invariance, and suitability of sum scores for the PHQ-9 and the GAD-7. Assessment. 2022;29:355–66. PubMed

Svensson T, Madhawa K, Nt H, Chung U-i, Svensson AK. Validity and reliability of the Oura ring generation 3 (Gen3) with Oura sleep staging algorithm 2.0 (OSSA 2.0) when compared to multi-night ambulatory polysomnography: A validation study of 96 participants and 421,045 epochs. Sleep Med. 2024;115:251–63. PubMed

Titone MK, Depp C, Klaus F, Carrasco J, Young JW, Eyler LT. The interplay of daily affect and impulsivity measured by mobile surveys in bipolar disorder. Int J Bipolar Disord. 2022;10:25. PubMed PMC

Tohen M, Calabrese JR, Sachs GS, Banov MD, Detke HC, Risser R, Baker RW, Chou JC-Y, Bowden CL. Randomized, Placebo-Controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine. Am J Psychiatry. 2006;163:247–56. PubMed

Vieta E, Suppes T, Eggens I, Persson I, Paulsson B, Brecher M. Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126). J Affect Disord. 2008;109:251–63. PubMed

Wadle LM, Ebner-Priemer UW. Smart digital phenotyping. Eur Neuropsychopharmacol. 2023;76:1–2. PubMed

Walsh RFL, Smith LT, Titone MK, Ng TH, Goel N, Alloy LB. The relationship between physical activity States and depressive symptoms: using ambulatory assessment to characterize day-to-day associations among individuals with and without bipolar spectrum disorder. Depress Anxiety. 2022;39:835–44. PubMed PMC

Wichers M. The dynamic nature of depression: a new micro-level perspective of mental disorder that Meets current challenges. Psychol Med. 2014;44:1349–60. PubMed

Wichers M, Peeters F, Rutten BP, Jacobs N, Derom C, Thiery E, Delespaul P, van Os J. A time-lagged momentary assessment study on daily life physical activity and affect. Health Psychol. 2012;31:135–44. PubMed

Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429–35. PubMed

Zimmerman M, Posternak MA, Chelminski I. Defining remission on the Montgomery-Asberg depression rating scale. J Clin Psychiatry. 2004;65:163–8. PubMed