title: Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging.
abstract: Anxiety disorders increase risk for the early development of several diseases of aging. Elevated inflammation, a common risk factor across diseases of aging, may play a key role in the relationship between anxiety and physical disease. However, the neurobiological mechanisms linking anxiety with elevated inflammation remain unclear. In this review, we present a neurobiological model of the mechanisms by which anxiety promotes inflammation. Specifically we propose that exaggerated neurobiological sensitivity to threat in anxious individuals may lead to sustained threat perception, which is accompanied by prolonged activation of threat-related neural circuitry and threat-responsive biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory response. Over time, this pattern of responding can promote chronic inflammation through structural and functional brain changes, altered sensitivity of immune cell receptors, dysregulation of the HPA axis and ANS, and accelerated cellular aging. Chronic inflammation, in turn, increases risk for diseases of aging. Exaggerated neurobiological sensitivity to threat may thus be a treatment target for reducing disease risk in anxious individuals.
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA, USA. aoife.odonovan@ucsf.edu
authors.forename: Aoife
authors.initials: A
authors.lastname: O'Donovan
authors.forename: George M
authors.initials: GM
authors.lastname: Slavich
authors.forename: Elissa S
authors.initials: ES
authors.lastname: Epel
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Neylan
mesh_terms: D000375:Aging / Q000502:physiology* / Q000523:psychology*; D000818:Animals; D001008:Anxiety Disorders / Q000150:complications* / Q000503:physiopathology / Q000523:psychology; D001341:Autonomic Nervous System / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D059333:Central Nervous System Sensitization / Q000502:physiology*; D005239:Fear / Q000502:physiology / Q000523:psychology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology / Q000523:psychology; D008959:Models, Neurological; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D012307:Risk Factors