Physical Activity Trajectories Preceding Incident Major Depressive Disorder Diagnosis Using Consumer Wearable Devices in the All of Us Research Program: Case-Control Study (Preprint)

BACKGROUND Low physical activity is a well-established risk factor for major depressive disorder (MDD). However, how physical activity changes in the months preceding a first clinical diagnosis of MDD has not been well explored, particularly when assessed using long-term, objective measures collected in real-world settings. OBJECTIVE This study aimed to characterize trajectories of wearable-measured physical activity during the year preceding incident MDD diagnosis. METHODS We conducted a retrospective nested case-control study using linked electronic health record (EHR) and consumer wearable data (Fitbit) from the All of Us Research Program. Adults with at least 6 months of valid Fitbit physical activity data in the 12 months preceding diagnosis were eligible. Incident MDD cases were identified based on a first recorded EHR diagnosis and matched to MDD-free controls on age, sex, body mass index, and time of diagnosis, with up to four controls per case. Daily step counts and moderate-to-vigorous physical activity (MVPA) were aggregated into monthly averages. Linear mixed-effects models were used to compare pre-diagnostic physical activity trajectories between cases and controls over a retrospective time scale from −12 to 0 months. Among cases, within-person contrasts were used to identify when physical activity levels first showed statistically significant deviations relative to levels observed 12 months before diagnosis. Exploratory analyses examined whether pre-diagnostic trajectories differed by sex, age, and body mass index. RESULTS The analytic cohort included 4,104 participants (829 incident MDD cases and 3,275 matched controls; 81.7% women; median age 48.4 years). Compared with controls, individuals who developed MDD exhibited consistently lower overall physical activity levels and significant downward trajectories in both daily step counts and MVPA during the year preceding diagnosis (global trajectory tests, P < .001 for both outcomes). Among cases, statistically significant changes in daily step counts emerged approximately 4 months before diagnosis, whereas significant changes in MVPA emerged approximately 5 months before diagnosis. Furthermore, exploratory analyses suggested heterogeneity in pre-diagnostic trajectories across demographic subgroups, including steeper declines among men, more pronounced reductions in activity intensity at older ages, and persistently lower activity levels with flatter trajectories among individuals with obesity. CONCLUSIONS In this large cohort with linked wearable and clinical data, sustained within-person declines in physical activity emerged several months before incident MDD diagnosis. These findings suggest that longitudinal monitoring of physical activity using consumer wearable devices may provide clinically relevant early signals to support risk stratification, targeted prevention, and earlier intervention for MDD.