Treatment-resistance is a signaling problem. The Signal Loss Model explains how therapeutic change fails to hold when cognition, neuroimmune regulation, and reward become biologically uncoupled.

Most accounts of treatment-resistance describe the failure from the outside. They catalogue non-response, relapse, partial remission, and the limits of existing modalities. The Signal Loss Model asks a different question: what signal was supposed to produce durable change, and where did that signal degrade?

SLM traces treatment-resistance as a three-mechanism cascade: Untethered Cognition, Neuroimmune Dysregulation, and Pursuit-Reward Decoupling. Together, these mechanisms describe a clinical pattern in which the person can understand the problem, remain biologically locked in it, and lose access to felt reward even while continuing to function. The model offers a testable vocabulary for how treatment loses force between insight, biology, motivation, and durable change. It works one level below symptoms, at the mechanisms that decide whether change holds.