Empirical Data and Pan-Ancestry Validation Methodology of the Bioenergetic Stability Index (ISB)

This document provides the empirical validation and computational methodology for the Bioenergetic Stability Index (ISB) framework. It bridges theoretical thermodynamic models with real-world clinical and genomic data to mechanistically reconstruct Major Depressive Disorder (MDD) as a systemic mitochondrial shutdown. Utilizing an empirically-driven in silico Monte Carlo simulation (N=30,000), the study extracts and translates parameters from Q1-scale literature regarding astrocytic ATP depletion, glutamate excitotoxicity, and peripheral allostatic load (Gastroesophageal Reflux Disease and hypocapnia). Furthermore, a Pan-Ancestry genomic simulation reveals significant Gene-Environment (GxE) interactions. The analysis demonstrates that East Asian (EAS) populations exhibit extreme genetic vulnerability (80.1% metabolic collapse rate) to vagal-induced thermodynamic failure under borderline stress, compared to European (EUR) and African (AFR) cohorts. These findings mathematically validate the ISB's Saddle-Node Bifurcation topology and expose critical Eurocentric biases in current psychiatric diagnostic thresholds.