Stress dysfunctions as a unifying paradigm for illness: Repairing relationships instead of individuals as a new gateway for medicine

SummaryStress has been implicated as a risk factor for most diseases, but a mechanistic explanation behind such associations remains elusive. As emergent responses to stress, adaptations range from acute responses where extant system capabilities mitigate current stress, to longer-term responses where system plasticity buffers against future stress. The long compendium of human ailments manifests through a much shorter set of symptoms that may operate through the stress axis. We propose a unifying ontology for human illnesses that classifies stress dysfunctions according to types of Darwinian dysfunction – inadequate response with adequate adaptation, inadequate adaptation, inappropriate adaptation, and epiphenomena of adaptation. Examples include cancer as a bystander effect of increased biologic plasticity in response to stress, and infectious illness as a manifestation of mutually escalating stress in an otherwise commensal relationship between hosts and microbes. We explore the contributing role of man-made stresses that have emerged as humans increasingly remodel their environment. Examples include biologic decompensation associated with reliance on technology to buffer stress, and behavioral stress caused by the dislocation of kin networks that promotes illegitimate signaling. Dysfunctional relationships engender stress not only among humans, but also among individual organs; heart failure, renal failure, and carotid stenosis may represent examples of such conditions. If stress dysfunction is the Occam’s razor of human illnesses, and derangements in biologic relationships induce stress dysfunctions, then the study of relationships – an incarnation of systems biology – may represent a new gateway for medicine.