Background This Zenodo entry presents the open-access report Mechanistic Validation of Constraint Dynamics: From Thermodynamic Necessity to Clinical Prediction (January 2026), authored by Matthew Cator. The 3-page report extends the biophysical framework introduced in The Outlines of Sanity (Cator, 2025), which reframes sanity not as a passive baseline but as an actively maintained attractor state governed by physical constraints. The framework proposes that coherent cognition depends on three orthogonal constraints: Spatial Lattice (Λ): metric spatial encoding, associated with entorhinal grid-cell structure Temporal Strobe (Γ): temporal binding via ~40 Hz gamma oscillations Metabolic Anchor (Ω): energetic stabilization mediated by autonomic and vagal regulation Mental illness is modeled not as symptom accumulation but as a predictable thermodynamic degradation of these constraints. A central contribution of the report is the concept of thermodynamic inversion: high-cost systems (particularly Γ) fail earliest under metabolic stress because they operate with the smallest safety margins, challenging traditional load-shedding assumptions in psychiatry. The report integrates recent empirical findings from Wang et al. (PNAS, 2026), which show that 40 Hz sensory stimulation in aged primates drives amyloid-β clearance. These results provide mechanistic support for the framework’s claim that oscillatory dynamics are not epiphenomenal, but play an active role in structural and metabolic maintenance. A formal master equation is introduced in which self-awareness (the Mirror, M) emerges as a function of constraint volume V(t) = Λ̃(t) · Γ̃(t) · Ω̃(t), collapsing when any single constraint degrades. Clinically, the report outlines a falsifiable psychosis prodrome cascade, identifying a potential 4–12 week intervention window using biomarkers such as reduced 40 Hz auditory steady-state response (ASSR) phase-locking and disrupted theta–gamma coupling. The work motivates prospective testing of constraint-failure sequences and supports a shift from symptom management toward constraint restoration. This contribution is intended for researchers in computational neuroscience, biophysical psychiatry, thermodynamics, and cognitive science, and aims to provide a physically grounded bridge between theoretical models and clinical prediction. Keywords: Constraint Dynamics, biophysical psychiatry, gamma oscillations, entorhinal grid cells, vagal tone, thermodynamic fragility, psychosis prodrome, Alzheimer’s disease, depression, 40 Hz ASSR, metabolic clearance