Modeling Dyadic Interdependence in Endocrine Functioning: A Multilevel Machine Learning Study of Adults with Cancer and Their Caregivers.

OBJECTIVE

This study evaluated dyadic endocrine interdependence among cancer patients and their spousal caregivers using a machine learning (ML) framework that assesses how partner-level information improves prediction of individual stress biomarker responses.

METHODS

A multilevel ML framework was applied to 149 patient-caregiver dyads. Predictive performance was evaluated for mean and variability of diurnal slopes for cortisol, alpha-amylase, and DHEAS. Five regression models were compared across eight configurations incorporating PCA, correlation-based filtering, and data augmentation via leave-one-out cross-validation. Incremental dyadic signals were quantified via partial Spearman correlation, and predictor importance redistribution was characterized using SHAP-based decomposition.

RESULTS

Nonlinear methods (Extra Trees, Random Forest, Gradient Boosted Regression) yielded top-performing models for 11 of 12 outcomes with at least one significant model at 95% confidence ($\rho$ = 21.1% to 50.6%). For slope mean outcomes, targeted preprocessing converted negative or near-zero baseline correlations into significant predictions. Partner signal significance was biomarker-specific: at 90% confidence, mean outcome partner signals were significant for cortisol and DHEAS (8 of 11 models) but negligible for alpha-amylase (1 of 10), whereas variability partner signals were distributed across all three biomarkers (8 of 22 models). SHAP analysis revealed two structural signatures: mean outcomes showed an incremental magnitude pattern (AUC-ROC = 0.91), indicating a unidirectional predictive partner signal, whereas variability outcomes exhibited bilateral convergence (AUC-ROC = 0.90), indicating patterns consistent with interpersonal processes.

CONCLUSION

Dyadic interdependence in endocrine regulation manifests through distinct structural signatures for mean versus variability measures.

SIGNIFICANCE: This analytic framework offers a hypothesis-generating approach to identifying psychobiological pathways for improving health in oncology populations.