Dolphin
Senior Member (Voting Rights)
Post-Exposure Syndromes as State-Space Trapping. A set-theoretic perspective on PSSD and the post-exposure family.
April 2026
DOI: 10.5281/zenodo.19742086
Lab: Antonei B Csoka's Lab
Description
A growing class of illnesses shares a clinical signature that current pharmacovigilance is ill-equipped to detect: a transient exposure - a drug course, an infection, a trauma, a chemical event - initiates a chronic, multisystem phenotype that persists long after the initiating agent is cleared. Post-SSRI sexual dysfunction (PSSD), post-finasteride syndrome (PFS), Long COVID, ME/CFS, PTSD, and Gulf War illness are typically studied in isolation, yet they share persistence after cessation, multisystem heterogeneity, discordance with single-axis biomarkers, and nonlinear course.
This presentation argues that these conditions form a coherent family - Post-Exposure Syndromes (PES) - and that their shared structure is topological rather than molecular.
Using PSSD as the anchor case, we formalize each syndrome as a subset S ⊂ X of a high-dimensional, multi-omic organismic state space.
A PES is a trapped set T: a region forward-invariant under ordinary dynamics, exited only by non-ordinary perturbation. Exposures are modeled as operators Φₑ on state space; because these operators do not generally commute, exposure history and order become formally essential rather than incidental.
Aging is reframed in part as the slow integral of the exposome across the life course, with PES as its acute, focal crystallisations - same operator class, different timescale.
The framework yields falsifiable predictions (discrete state clustering, hysteresis under perturbation, measurable exposure-order effects) and reorients the clinical question from "what single pathway is broken?" to "what keeps this system in this state, and what would restore reachability?"
Four implications follow for pharmacovigilance: reforming adverse-event reporting to include post-discontinuation windows, establishing active surveillance cohorts for persistent syndromes, informed-consent language that names persistence risk, and modeling exposure history rather than point exposures.
