Auditing Construct Overlap in Explainable Machine Learning: Evidence from Burnout-Depression Prediction Across Student Cohorts

Explainable machine learning (XML) pipelines applied to composite mental health outcomes can produce apparently-robust, cross-population-stable risk hierarchies that are largely artefacts of how the outcome was constructed. We demonstrate this using an ElasticNet pipeline applied to 886 medical students at the University of Lausanne (primary cohort, 2022), validated across 2,580 longitudinal observations at three time points and 701 non-medical students from eight faculties; all three datasets share identical instruments. The pipeline produces a hierarchy in which trait anxiety and health satisfaction dominate wherever the outcome is measured, with Kendall $τ= 1.0$ for the top-two positions across all five evaluation sets and consistent transfer performance ($R^2$: 0.41-0.49). Two residualization experiments, which isolate shared variance between correlated variables via regression, reveal the mechanism: when trait anxiety (STAI-T) is residualized against the co-included depression subscale (CES-D, $r = 0.72$), model $R^2$ drops from 0.41 to 0.16 and STAI-T falls from rank 1 to rank 6; when burnout subscales are residualized against CES-D, $R^2$ collapses to 0.016. Prediction intervals average 35.4 units on a 0-100 scale (2.4 outcome standard deviations), independently ruling out individual-level deployment. The residualization protocol is the paper's transferable contribution: any XAI study combining correlated predictor and outcome constructs should apply this check before interpreting apparent stability as a finding.

Estimating Treatment Effects for Depression in Longitudinal Therapy Switching Settings

Depression treatment often requires switching medications due to inadequate response or adverse effects. Estimating individualized treatment effects in this setting is challenging because treatment assignment is confounded by patient characteristics, switching induces time-varying selection, and counterfactual outcomes are not observed in follow-up data. Using a proprietary longitudinal major depressive disorder (MDD) clinical trial dataset, we formulate a next-visit counterfactual prediction task to estimate Hamilton Depression Rating Scale (HAMD-17) total scores under alternative treatments. We benchmark 8 estimators, including meta-learners, residual-based methods, and tree-based approaches. Causal Forest (CF) demonstrates the most favorable and consistent performance across all criteria. Our analysis shows that symptom benefits concentrate in specific switch directions, with dose intensification being generally beneficial. Notably, we identify a counterintuitive exception where a lower-intensity regimen outperforms a higher-intensity alternative for specific patient subsets. While crude observational comparisons substantially overstate gains, confounding-adjusted estimates yield modest, actionable magnitudes. These findings provide prospectively testable candidates for clinical decision support in depression care.

PSI-Bench: Towards Clinically Grounded and Interpretable Evaluation of Depression Patient Simulators

Patient simulators are gaining traction in mental health training by providing scalable exposure to complex and sensitive patient interactions. Simulating depressed patients is particularly challenging, as safety constraints and high patient variability complicate simulations and underscore the need for simulators that capture diverse and realistic patient behaviors. However, existing evaluations heavily rely on LLM-judges with poorly specified prompts and do not assess behavioral diversity. We introduce PSI-Bench, an automatic evaluation framework that provides interpretable, clinically grounded diagnostics of depression patient simulator behavior across turn-, dialogue-, and population-level dimensions. Using PSI-Bench, we benchmark seven LLMs across two simulator frameworks and find that simulators produce overly long, lexically diverse responses, show reduced variability, resolve emotions too quickly, and follow a uniform negative-to-positive trajectory. We also show that the simulation framework has a larger impact on fidelity than the model scale. Results from a human study demonstrate that our benchmark is strongly aligned with expert judgments. Our work reveals key limitations of current depression patient simulators and provides an interpretable, extensible benchmark to guide future simulator design and evaluation.