Multimodal Digital Phenotyping Study in Patients With Major Depressive Episodes and Healthy Controls (Mobile Monitoring of Mood): Observational Longitudinal Study
Authors: Aledavood Talayeh , Luong Nguyen , Baryshnikov Ilya , Darst Richard , Heikkilä Roope , Holmén Joel , Ikäheimonen Arsi , Martikkala Annasofia , Riihimäki Kirsi , Saleva Outi , Triana Ana Maria , Isometsä Erkki 
Published: December 2024

Background
Mood disorders are among the most common mental health conditions worldwide. Wearables and consumer-grade personal digital devices create digital traces that can be collected, processed, and analyzed, offering a unique opportunity to quantify and monitor individuals with mental disorders in their natural living environments.

Objective
This study comprised (1) 3 subcohorts of patients with a major depressive episode, either with major depressive disorder, bipolar disorder, or concurrent borderline personality disorder, and (2) a healthy control group. We investigated whether differences in behavioral patterns could be observed at the group level, that is, patients versus healthy controls. We studied the volume and temporal patterns of smartphone screen and app use, communication, sleep, mobility, and physical activity. We investigated whether patients or controls exhibited more homogenous temporal patterns of activity when compared with other individuals in the same group. We examined which variables were associated with the severity of depression.

Methods
In total, 188 participants were recruited to complete a 2-phase study. In the first 2 weeks, data from bed sensors, actigraphy, smartphones, and 5 sets of daily questions were collected. In the second phase, which lasted up to 1 year, only passive smartphone data and biweekly 9-item Patient Health Questionnaire data were collected. Survival analysis, statistical tests, and linear mixed models were performed.

Results
Survival analysis showed no statistically significant difference in adherence. Most participants did not stay in the study for 1 year. Weekday location variance showed lower values for patients (control: mean –10.04, SD 2.73; patient: mean –11.91, SD 2.50; Mann-Whitney U [MWU] test P=.004). Normalized entropy of location was lower among patients (control: mean 2.10, SD 1.38; patient: mean 1.57, SD 1.10; MWU test P=.05). The temporal communication patterns of controls were more diverse compared to those of patients (MWU test P<.001). In contrast, patients exhibited more varied temporal patterns of smartphone use compared to the controls. We found that the duration of incoming calls (β=–0.08, 95% CI –0.12 to –0.04; P<.001) and the SD of activity magnitude (β=–2.05, 95% CI –4.18 to –0.20; P=.02) over the 14 days before the 9-item Patient Health Questionnaire records were negatively associated with depression severity. Conversely, the duration of outgoing calls showed a positive association with depression severity (β=0.05, 95% CI 0.00-0.09; P=.02).

Conclusions
Our work shows the important features for future analyses of behavioral markers of mood disorders. However, among outpatients with mild to moderate depressive disorders, the group-level differences from healthy controls in any single modality remain relatively modest. Therefore, future studies need to combine data from multiple modalities to detect more subtle differences and identify individualized signatures. The high dropout rates for longer study periods remain a challenge and limit the generalizability.