Stress and the "extended" autonomic system Author: David S Goldstein1 Affiliation: <sup>1</sup> Autonomic Medicine Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Autonomic Medicine Section, CNP/DIR/NINDS/NIH, 9000 Rockville Pike MSC-1620, Building 10 Room 8N260, Bethesda, MD 20892-1620, USA.. Electronic address: goldsteind@ninds.nih.gov. Conference/Journal: Auton Neurosci Date published: 2021 Oct 2 Other: Volume ID: 236 , Pages: 102889 , Special Notes: doi: 10.1016/j.autneu.2021.102889. , Word Count: 257 This review updates three key concepts of autonomic neuroscience-stress, the autonomic nervous system (ANS), and homeostasis. Hans Selye popularized stress as a scientific idea. He defined stress variously as a stereotyped response pattern, a state that evokes this pattern, or a stimulus that evokes the state. According to the "homeostat" theory stress is a condition where a comparator senses a discrepancy between sensed afferent input and a response algorithm, the integrated error signal eliciting specific patterns of altered effector outflows. Scientific advances since Langley's definition of the ANS have incited the proposal here of the "extended autonomic system," or EAS, for three reasons. (1) Several neuroendocrine systems are bound inextricably to Langley's ANS. The first to be described, by Cannon in the early 1900s, involves the hormone adrenaline, the main effector chemical of the sympathetic adrenergic system. Other neuroendocrine systems are the hypothalamic-pituitary-adrenocortical system, the arginine vasopressin system, and the renin-angiotensin-aldosterone system. (2) An evolving body of research links the ANS complexly with inflammatory/immune systems, including vagal anti-inflammatory and catecholamine-related inflammasomal components. (3) A hierarchical network of brain centers (the central autonomic network, CAN) regulates ANS outflows. Embedded within the CAN is the central stress system conceptualized by Chrousos and Gold. According to the allostasis concept, homeostatic input-output curves can be altered in an anticipatory, feed-forward manner; and prolonged or inappropriate allostatic adjustments increase wear-and-tear (allostatic load), resulting in chronic, stress-related, multi-system disorders. This review concludes with sections on clinical and therapeutic implications of the updated concepts offered here. Keywords: Allostasis; Autonomic; Dyshomeostasis; Homeostasis; Stress. PMID: 34656967 DOI: 10.1016/j.autneu.2021.102889