Conceptual review reveals fragmentation of stress mechanisms across clinical specialties in complex illness, highlighting the need for whole-organism regulatory models.
Modern medicine did not reject stress biology; it distributed its mechanisms across specialties. This paper argues that specialization increased mechanistic precision while leaving the adaptive coordination of the whole organism without clear explanatory ownership. It synthesizes research on allostasis, predictive regulation, interoception, energetic constraint and network physiology, and distinguishes five features often collapsed in stress research: regulatory architecture, current physiological state, accumulated history, present regulatory capacity and environmental fit. These distinctions clarify why similar biomarkers or observable performance may reflect different mechanisms, costs and intervention needs, particularly in multimorbidity, persistent illness and neurodivergence. The paper proposes a practical agenda: define the stress construct being measured; prioritize dynamics, coupling and recovery; incorporate environmental demand into causal models; model heterogeneity rather than averaging it away; and preserve specific diagnosis. Stress should widen clinical inquiry, not terminate it. Peer-review status: This independent scholarly paper has not been peer-reviewed.
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Lori Hogenkamp (2026) studied this question.
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