The Effect of Bipolar Disorder Illness Course on Physiological Digital Signals: Observational Study
Year: 2026
Type: article
Abstract: Background Although bipolar disorder (BD) lacks objective biomarkers of illness progression, wearable devices enable continuous, real-world collection of physiological digital biosignals, offering a promising approach to address this gap. Measures such as electrodermal activity (EDA) and heart rate variability (HRV) fluctuate with mood state and symptom severity. Previous studies have reported reduced EDA during depressive episodes and increased HRV following symptom resolution after acute mood episodes. Furthermore, greater illness burden in BD has been associated with lower HRV, suggesting that digital biosignals may capture not only state-related changes but also aspects of illness course. Objective This study investigated whether naturalistic EDA and heart rate (HR) profiles differ according to illness course variables in BD—including diagnosis, predominant polarity, years since onset, and lifetime number of episodes—in euthymic patients, to evaluate their potential as illness course biomarkers. Methods This cross-sectional post hoc analysis used data from 80 euthymic patients on the BD spectrum from the INTREPIBD-TIMEBASE cohort. Participants were recruited at Hospital Clínic de Barcelona (Spain) between 2021 and 2024 and wore an Empatica E4 wristband for 48 hours in naturalistic settings. Inclusion criteria comprised a current or past DSM-5 ( Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition) diagnosis of BD confirmed by structured interview and sustained euthymia. We examined the effects of 4 illness course variables (diagnosis, predominant polarity, years since onset, and number of lifetime episodes) on 3 biosignals (mean EDA, EDA peaks per minute, and HR) using generalized additive models. Interactions between illness course variables and circadian patterns were also assessed. All models were adjusted for age, sex, and current antipsychotic use and included a participant-specific random effect. Results Of the 80 participants, 49 (61.3%) were female; participants’ mean age was 46.9 (SD 14.1) years. After adjustment for covariates and multiple comparisons, no significant associations were observed between illness course variables and EDA or HR. In sensitivity analyses excluding patients with schizoaffective disorder (n=75), years since illness onset and predominant polarity were associated with EDA peaks per minute after multiple comparison correction. Specifically, patients with more than 22 years since illness onset had fewer EDA peaks compared with other groups (β=−1.06, 95% CI −1.71 to −0.41; P =.001). No significant interactions were found between illness course variables and circadian patterns of EDA or HR. Conclusions To our knowledge, this is the first study to examine the association between illness course variables and EDA and HR recorded in naturalistic settings in BD. In contrast to prior findings linking illness burden with HRV, our results suggest that years since illness onset may show modest associations with phasic EDA activity. These findings indicate that digital biosignals may be more sensitive to state-related changes than to illness course characteristics, limiting their use as longitudinal biomarkers of disease progression.
Source: JMIR Mental Health
DOI: 10.2196/94737
Authors: Clàudia Valenzuela-Pascual, Marina Garriga, Roger Borràs, Ruth Voltà-Solerdelcoll, Marta Korniyenko, Ariadna Mas, Clara Escala, Peter De Looff, Gerard Anmella, Antonio Benabarre, Isabella Pacchiarotti, Anna Bastidas, Isabel Agasi, Meritxell González-Campos, Iria Grande, Cristina Romero-López-Alberca, Cecilia Muñoz-Doña, Ana Catalan, Esteban Sepulveda, Eduard Vieta, Marc Valentí, Diego Hidalgo-Mazzei
Institutions: Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Radboud University Nijmegen, Tilburg University, Universidad de Cádiz, Biomedical Research and Innovation Institute of Cadiz, Hospital Universitario Puerta del Mar, University of the Basque Country, Hospital de Basurto, Institut Pere Mata, Institut de Recerca Biomèdica Catalunya Sud, Universitat Rovira i Virgili
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,750
Funders: U.S. Department of Defense, Patient-Centered Outcomes Research Institute, Wellcome Trust, UK Research and Innovation, Centres de Recerca de Catalunya, Equity Trustees, European Commission, Generalitat de Catalunya, Lundbeckfonden, State Government of Victoria, Ministerio de Ciencia e Innovación, Centro de Investigación Biomédica en Red de Salud Mental, Servier, H. Lundbeck A/S, National Health and Medical Research Council, Instituto de Salud Carlos III, European Regional Development Fund, European Social Fund, Congressionally Directed Medical Research Programs, Cilag, Medical Research Future Fund, NextGenerationEU
OpenAlex ID: W7213327609