Beyond Executive Dysfunction: A Systems and Human Factors Engineering Model of Postural Fatigue, Pharmacokinetic Dispersion, and Multisystemic Reactivity in Hypermobile Neurodivergence (AuDHD)

Contemporary clinical practice approaches Autism with Attention-Deficit/Hyperactivity Disorder (AuDHD), Hypermobility Spectrum Disorders / hypermobile Ehlers-Danlos Syndrome (HSD/hEDS), orthostatic dysautonomia (e.g., POTS), and Mast Cell Activation Syndrome (MCAS) as disconnected, incidental comorbidities or psychogenic somatizations. This siloed perspective results in multi-decade diagnostic delays, iatrogenic pharmacological failures, and severe clinical invalidation—particularly among twice-exceptional (2e) individuals whose high cognitive capacity compensates for structural breakdowns at immense physiological cost. This Concept Note introduces an epistemological shift grounded in Systems Engineering and Human Factors Ergonomics. The proposed framework models these manifestations not as separate pathologies, but as the integrated expression of a single neuroconnective phenotype driven by atypical fibrillar collagen dynamics across four core operational domains: Fluid Hydrodynamics & Circulatory Capacitance (microvascular compliance, splanchnic/lower-limb venous pooling, and adrenergic overdrive); Mechanosensory Gating & Proprioceptive Noise (loss of ligamentous mechanoreceptive calibration forcing prefrontal executive compensation); Pharmacokinetic Dispersion (rapid interstitial dissipation preventing nerve-block thresholds with delayed systemic central depression); Immunological Sentinel Reactivity (matrix-destabilized mastocytes driving neurogenic hyper-reactivity). Targeted for interdisciplinary collaboration across Anesthesiology, Neurodevelopment, and Occupational Ergonomics, this paper establishes scientific priority, intellectual prior art, and translational research hypotheses.