Higher Whole-Blood Local Spectral Entropy in Women with Fibromyalgia in a Single-Cohort Reanalysis of GSE221921

A retrospective, single-cohort, hypothesis-generating computational reanalysis of the public NCBI Gene Expression Omnibus whole-blood transcriptomic cohort GSE221921 (96 fibromyalgia / 93 control). For each sample we compute the local covariance spectral (von Neumann) entropy — the base-2 Shannon entropy of the normalized eigenvalue spectrum of the sample's local transcriptomic neighborhood — and evaluate it in two deliberately separated tiers because the cohort is strongly sex-confounded (fibromyalgia 91 female / 5 male; control 41 female / 52 male). As a direction-agnostic structural anchor, full-cohort entropy differs between groups (median difference +0.195 bits, bootstrap 95% CI [+0.070, +0.291], two-sided Welch p = 1.1×10⁻⁵), a magnitude that is partly tail-inflated by a low-entropy control-arm cluster and is therefore not treated as the headline. The load-bearing directional finding — fibromyalgia entropy higher than control — is established within the female stratum (mean difference +0.147 bits, Cohen's d = +0.62, bootstrap 95% CI [+0.042, +0.273]) and corroborated by a sex-residualized regression, surviving removal of the predominantly male control-arm tail. With no cell-composition control, an intrinsic transcriptional-state reading cannot be separated from a leukocyte shift, and severity and treatment-response associations were tested and not supported; this is not a diagnostic, prognostic, severity, or treatment-selection tool.