Abstract
Burnout- and depression-like functional collapse is usually interpreted through isolated biological systems, such as hypothalamic–pituitary–adrenal signalling or inflammation. This may miss state-dependent coordination across systems, particularly within individuals whose cognitive and/or sensory processing carries a high physiological cost. High Processing Cost Phenotypes (HPCPh), previously described by us, span neurodivergent and high-ability profiles, including autism, attention-deficit/hyperactivity disorder, learning disorders and giftedness.We present a systems-physiology framework derived from longitudinal within-person observation of 12 individuals followed in routine private clinical practice, comprising 532 laboratory collections over 10–25 years per person. Each collection is read as a physiological state and successive collections as transitions. Across the series, multiple regulatory systems changed configuration within individuals, and physiologically related marker pairs repeatedly departed from their expected relations. In three examples, multisystem configurations shifted back after changes in context over days, months or one year.We interpret this pattern as multisystem regulatory containment: a coordinated reduction and redistribution of physiological throughput when information-processing demand exceeds sustainable capacity, rather than failure of a single system. We also introduce simple visual tools for reading routine laboratory data longitudinally within the person.This retrospective case series is descriptive and hypothesis-generating. It does not establish specificity to HPCPh or normative longitudinal trajectories. Its purpose is to make a recurrent, context-responsive and potentially reversible physiological pattern visible and testable. If confirmed prospectively, this framework may be particularly relevant to neurodivergent and high-ability children and adults whose functional decline is poorly captured by conventional cross-sectional interpretation, and may inform both clinical care and the design of environments better matched to individual processing capacity. This may matter most in children, in whom such changes can have more lasting consequences.