Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 1;10(5):e137.
doi: 10.1192/bjo.2024.716.

Identifying digital biomarkers of illness activity and treatment response in bipolar disorder with a novel wearable device (TIMEBASE): protocol for a pragmatic observational clinical study

Gerard Anmella  1 , Filippo Corponi  2 , Bryan M Li  2 , Ariadna Mas  1 , Marina Garriga  1 , Miriam Sanabra  1 , Isabella Pacchiarotti  1 , Marc Valentí  1 , Iria Grande  1 , Antoni Benabarre  1 , Anna Giménez-Palomo  1 , Isabel Agasi  3 , Anna Bastidas  4 , Myriam Cavero  1 , Miquel Bioque  5 , Clemente García-Rizo  5 , Santiago Madero  6 , Néstor Arbelo  7 , Andrea Murru  1 , Silvia Amoretti  1 , Anabel Martínez-Aran  1 , Victoria Ruiz  3 , Yudit Rivas  3 , Giovanna Fico  1 , Michele De Prisco  1 , Vincenzo Oliva  1 , Aleix Solanes  8 , Joaquim Radua  9 , Ludovic Samalin  10 , Allan H Young  11 , Antonio Vergari  2 , Eduard Vieta  1 , Diego Hidalgo-Mazzei  1
Affiliations

Identifying digital biomarkers of illness activity and treatment response in bipolar disorder with a novel wearable device (TIMEBASE): protocol for a pragmatic observational clinical study

Gerard Anmella et al. BJPsych Open. .

Abstract

Background: Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions.

Aims: The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder.

Method: We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania (n = 12), depression (n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features (n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients.

Results: Recruitment is ongoing.

Conclusions: This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.

Keywords: Bipolar disorder; depression; digital biomarkers; mania; physiological data.

PubMed Disclaimer

Conflict of interest statement

G.A. has received CME-related honoraria or consulting fees from ADAMED, Angelini, Casen Recordati, Janssen-Cilag, Lundbeck, Lundbeck/Otsuka, Rovi and Viatris, with no financial or other relationship relevant to the subject of this article. G.A. is supported by a Juan Rodés 2023 grant (JR23/00050), a Rio Hortega 2021 grant (CM21/00017) and M-AES mobility fellowship (MV22/00058), from the Spanish Ministry of Health financed by the Instituto de Salud Carlos III (ISCIII) and co-financed by the Fondo Social Europeo Plus (FSE+). G.A. thanks the support of the Spanish Ministry of Health financed by the Instituto de Salud Carlos III (ISCIII) and co-financed by the European Social Fund+ (ESF+) (JR23/00050, MV22/00058, CM21/00017); the ISCIII (PI21/00340, PI21/00169); the Milken Foundation (PI046998); the Fundació Clínic per a la Recerca Biomèdica (FCRB) – Pons Bartan 2020 grant (PI04/6549), the Sociedad Española de Psiquiatría y Salud Mental (SEPSM); the Fundació Vila Saborit; and the Societat Catalana de Psiquiatria i Salut Mental (SCPiSM). F.C. and B.M.L. are supported by United Kingdom Research and Innovation (grant EP/S02431X/1), UKRI Centre for Doctoral Training in Biomedical AI at the University of Edinburgh, School of Informatics. I.P. has received CME-related honoraria or consulting fees from ADAMED, Janssen-Cilag and Lundbeck (unrelated to the present work). I.G. has received grants and served as consultant, advisor or CME speaker for the following entities: ADAMED, Angelini, Casen Recordati, Ferrer, Gedeon Richter, Janssen Cilag, Lundbeck, Lundbeck-Otsuka, Luye and SEI Healthcare, outside the submitted work. M.G. has received grants and served as consultant, advisor or CME speaker for the following entities: Ferrer, Janssen Cilag, Lundbeck and Viatris, with no financial or other relationship relevant to the subject of this article. I.G. thanks the support of the Spanish Ministry of Science and Innovation (MCIN) (PI19/00954) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación y el Fondos Europeos de la Unión Europea (FEDER, FSE, Next Generation EU/Plan de Recuperación Transformación y Resiliencia (PRTR)); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); and the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2021 SGR 01358), CERCA Programme/ Generalitat de Catalunya as well as the Fundació Clínic per la Recerca Biomèdica (Pons Bartran 2022-FRCB_PB1_2022). M.G. thanks the support of the Spanish Ministry of Science and Innovation (MCIN) (PI21/00340) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdirección General de Evaluación y el Fo+ndos Europeos de la Unión Europea (FEDER, FSE, Next Generation EU/Plan de Recuperación Transformación y Resiliencia (PRTR)); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM) and the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), CERCA Programme/Generalitat de Catalunya. A.G.-P. has received CME-related honoraria, or consulting fees from Janssen-Cilag, Lundbeck, Casen Recordati and Angelini, with no financial or other relationship relevant to the subject of this article. M.C. has received grants and served as consultant, advisor or CME speaker for the following entities: Lundbeck, Esteve or Pfizer, with no financial or other relationship relevant to the subject of this article. N.A. has received CME-related financing from Janssen-Cilag, Lundbeck, Adamed, Pfizer, Angelini and Boston Scientific, outside the submitted work. M.B. has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of or has received honoraria from talks and/or consultancy of Adamed, Angelini, Casen-Recordati, Exeltis, Ferrer, Janssen, Lundbeck, Neuraxpharm, Otsuka, Pfizer and Sanofi. M.B. thanks the support from the Spanish Ministry of Health, Instituto de Salud Carlos III (PI20/01066). S.M. has received CME-related honoraria or consulting fees from Janssen-Cilag, Lundbeck, Lundbeck/Otsuka and Angelini, with no financial or other relationship relevant to the subject of this article. S.M. is supported by the grant ‘Contracte de Recerca Emili Letang-Josep Font’ given by Hospital Clinic. A. Murru has received grants and served as consultant, advisor or CME speaker for the following entities: Angelini, Idorsia, Lundbeck, Pfizer and Takeda, with no financial or other relationship relevant to the subject of this article. A. Murru thanks the support of the Spanish Ministry of Science and Innovation (PI19/00672) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). S.A. has been supported by a Sara Borrell contract (CD20/00177), funded by Instituto de Salud Carlos III (ISCIII) and co-funded by European Social Fund 'Investing in your future'. A.M.-A. thanks the support of the Spanish Ministry of Science and Innovation (PI18/00789, PI21/00787) integrated into the Plan Nacional de I+D+I and co-financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the ISCIII; the CIBER of Mental Health (CIBERSAM); the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00177. J.R. is supported by a Miguel Servet II contract (CPII19/00009), funded by Instituto de Salud Carlos III (ISCIII) and co-funded by European Social Fund 'Investing in your future'. L.S. has received honoraria or consulting fees from Boehringer-Ingelheim, Janssen, Lundbeck/Otsuka, Rovi and Sanofi-Aventis, with no financial or other relationship relevant to the subject of this article. A.H.Y. has received honoraria for lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders, with no financial or other relationship relevant to the subject of this article. E.V. has received research support from or served as consultant, adviser or speaker for AB-Biotics, Abbott, Abbvie, Adamed, Angelini, Biogen, Celon, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Glaxo SmithKline, Janssen, Lundbeck, Organon, Otsuka, Rovi, Sage Pharmaceuticals, Sanofi-Aventis, Shire, Sunovion, Takeda and Viatris, out of the submitted work. E.V. thanks the support of the Spanish Ministry of Science, Innovation and Universities (PI15/00283, PI18/00805, PI19/00394, CPII19/00009) integrated into the Plan Nacional de I+D+I and co-financed by the Instituto de Salud Carlos III (ISCIII)-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), the ISCIII, the CIBER of Mental Health (CIBERSAM), the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365) and the CERCA Programme/Generalitat de Catalunya. We would like to thank the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357. D.H.-M. has received CME-related honoraria and served as consultant for Abbott, Angelini, Ethypharm Digital Therapy and Janssen-Cilag, with no financial or other relationship relevant to the subject of this article. I.P. and A.H.Y. did not take part in the review or decision-making process of this paper. All other authors report no financial or other relationship relevant to the subject of this article.

Figures

Fig. 1
Fig. 1
Study design. Group A: patients with acute affective episodes. A consecutive group of 48 individuals: A1: 12 manic episodes in bipolar disorder. A2: 24 major depressive episodes, of which 12 were bipolar disorder and 12 were MDD. A3: 12 mixed features manic episodes in bipolar disorder. Patients will be monitored with a wearable device at four time points: T0, acute affective episodes (manic, depressive, and mixed) at the beginning of hospital admission; T1, response of the episode, usually at mid-admission; T2, remission of the episode, usually at the end of admission or shortly after discharge; and T3, recovery (2 months after sustained remission), at out-patient setting after discharge. Recordings will be according to the psychopathological status of patients (acute, response, remission, recovery), so that the proposed timings during admission (beginning, mid-admission, end of admission, after discharge) are oriented according to usual clinical experience. Group B: patients with euthymia, an independent group of 24 consecutive patients (12 bipolar disorder and 12 MDD). They will be monitored at the out-patient clinic. Group C: 12 healthy controls will be monitored during their usual daily routine. CGI-S, Clinical Global Impression Scale: Severity Of Illness; HDRS, Hamilton Depression Rating Scale total score; IPAQ, Short Scale International Physical Activity Questionnaire; MDD, major depressive disorder; PANSS, Positive And Negative Syndrome Scale; SCID-5-RV, Structured Clinical Interview for DSM-5, Research Version;SOFAS, Social and Occupational Functioning Assessment Scale; YMRS, Young Mania Rating Scale total score.
See this image and copyright information in PMC

References

    1. Vigo D, Thornicroft G, Atun R. Estimating the true global burden of mental illness. Lancet Psychiatry 2016; 3: 171–8. - PubMed
    1. Carvalho AF, Firth J, Vieta E. Bipolar disorder. N Engl J Med 2020; 383(1): 58–66. - PubMed
    1. Martínez-Arán A, Vieta E, Reinares M, Colom F, Torrent C, Sánchez-Moreno J, et al. Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder. Am J Psychiatry 2004; 161(2): 262–70. - PubMed
    1. Crump C, Sundquist K, Winkleby MA, Sundquist J. Comorbidities and mortality in bipolar disorder: a Swedish national cohort study. JAMA Psychiatry 2013; 70(9): 931–9. - PubMed
    1. Holm M, Tanskanen A, Lähteenvuo M, Tiihonen J, Taipale H. Comparative effectiveness of mood stabilizers and antipsychotics in the prevention of hospitalization after lithium discontinuation in bipolar disorder. Eur Neuropsychopharmacol 2022; 61: 36–42. - PubMed