Cardiac rhythm development: A wearable device index of risk for physical and mental illness in adolescence

Technical Summary: Cardiac Rhythm Development as a Risk Index for Adolescent Illness

Problem Statement
The autonomic nervous system (ANS) undergoes significant maturation during adolescence, regulating cardiac activity into a distinct 24-hour rhythm. While prior research has established that heart rate generally decreases with age and that individual variability exists, the specific developmental trajectory of the shape of this rhythm remains poorly characterized. Furthermore, it is unknown whether individual differences in the development of this rhythm forecast the onset of psychiatric and cardiometabolic illnesses. Existing measurement approaches—brief laboratory recordings or discrete Holter parameters—fail to capture the continuous, diurnal shape of the rhythm. Consequently, there is a lack of large-scale, longitudinal data linking the cosinor-parameterized cardiac rhythm to transdiagnostic health risks in youth.

Methodology
The study utilized data from the Adolescent Brain Cognitive Development (ABCD) Study, analyzing three waves of Fitbit Charge HR2 data (Waves 2, 4, and 6; ages ~12, 14, and 16).

• Sample: The developmental analysis included 8,301 adolescents contributing 242,811 valid wear days. The prediction analysis compared 1,188 healthy controls against 1,360 adolescents who developed incident clinical elevations.
• Data Processing: Minute-level heart rate data were aggregated by clock hour. A single-component (24-hour) linear mixed-effects cosinor model was fitted to extract three rhythm parameters per session:
  • Mesor: The 24-hour rhythm-adjusted mean.
  • Amplitude: The peak-to-mean diurnal swing.
  • Acrophase: The clock time of the daily peak.
• Analytical Approach:
  • Developmental Trajectories: Generalized additive mixed models (GAMLSS) estimated age- and sex-specific curves, adjusting for physical activity, sleep, pubertal stage, demographics, and medication.
  • Co-development: Parallel-process latent growth curve models tested whether within-person changes in rhythm parameters tracked changes in psychopathology (depression, anxiety, externalizing) and cardiometabolic outcomes (BMI, blood pressure).
  • Clinical Onset Prediction: Hierarchical logistic regression models predicted the first clinical onset of disorders (defined by crossing clinical thresholds at Waves 4 or 6). Models controlled for demographics, baseline subthreshold symptoms, and behavioral covariates (steps, sleep) before entering rhythm parameters.

Key Results

• Developmental Trajectories: The cardiac rhythm changed substantially across adolescence. The mesor decreased significantly (approx. −1.80 bpm/year in males, −1.38 bpm/year in females), amplitude flattened, and acrophase shifted later (approx. 10 minutes/year).
  • Drivers: The decline in mesor was largely independent of behavioral factors (activity and sleep accounted for <8% of variance), suggesting intrinsic autonomic maturation. In contrast, the flattening of amplitude was largely explained by declining physical activity. Pubertal stage mediated approximately 32% of the sex difference in amplitude.
• Stability: The mesor was the most stable, trait-like parameter across waves (ICC = 0.56–0.61), followed by amplitude and acrophase.
• Co-development: Within-person changes in mesor were tightly coupled with changes in systolic blood pressure (slope-slope r = 0.89) and BMI (r = 0.36). For psychopathology, mesor changes covaried with depression and ADHD symptom trajectories, but not anxiety or externalizing problems.
• Prediction of Clinical Onset: A higher mesor in early adolescence (Wave 2) predicted the first onset of all five outcomes (depression, anxiety, externalizing, obesity, hypertension) two to four years later, even after controlling for demographics, baseline symptoms, and behavior.
  • Odds Ratios (OR): Higher mesor conferred risk for depression (OR=1.51), anxiety (1.48), externalizing (1.36), obesity (1.47), and hypertension (1.54).
  • Additional Risk Factors: Lower amplitude independently predicted hypertension and depression; later acrophase predicted anxiety. Day-to-day instability of the rhythm also conferred transdiagnostic risk.
  • Specificity: Most incident cases were non-comorbid (76.4% met threshold for a single condition), suggesting the rhythm indexes a shared physiological substrate rather than a specific comorbid subgroup.

Significance and Claims
The authors claim this study is the first to map the 24-hour cardiac rhythm longitudinally and at scale in adolescents, providing developmental growth charts for mesor, amplitude, and acrophase. The primary significance lies in identifying the 24-hour cardiac rhythm as a "passively measurable substrate of adolescent autonomic development" that indexes transdiagnostic risk.

Specifically, the paper claims that:

1. Prognostic Value: Individual differences in the development of the cardiac rhythm forecast the emergence of both psychiatric and cardiometabolic difficulties, extending beyond the variance explained by traditional demographic and behavioral variables.
2. Transdiagnostic Nature: A higher mesor serves as a broad risk marker across distinct domains (mental and physical health), supporting the hypothesis that ANS imbalance is a shared developmental risk factor.
3. Methodological Advance: By utilizing continuous passive monitoring via wearables and cosinor modeling, the study overcomes the limitations of static snapshots and discrete reference values, capturing the dynamic shape of the rhythm.

The authors maintain a modest tone regarding limitations, noting that the minute-level data cannot separate sympathetic and parasympathetic contributions and that the ABCD cohort is relatively healthy compared to clinical populations. They conclude that while the rhythm signals risk, future work is needed to determine if stratifying samples based on this data can lead to earlier, targeted prevention.