title: Tumor necrosis factor-alpha: is there a continuum of liability between stress, anxiety states and anorexia nervosa?
abstract: Since the time of Freud, psychiatry has embraced the proposition that physiological and/or psychological stress precipitates various psychiatric disorders. To this effect, we propose that a continuum of liability obtains between stress, anxiety states and anorexia nervosa--a continuum which is grounded on a cytokine profile common to each of these conditions. For example, the biological response to stress, anxiety states and anorexia nervosa includes the elevation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), and downregulation of interferon-gamma (IFN-gamma). Sustained elevation of IL-1 beta and TNF-alpha dysregulates both somatostatin and insulin secretion, the latter of which influences regional cerebral blood flow (rCBF) and brain energy metabolism. In addition, IL-1 beta and TNF-alpha influence the expression of certain crucial neuropeptides, which are known to be associated with anxiety states and anorexia nervosa. These neuropeptides include: beta-endorphin, cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). beta-endorphin effects glucose metabolism in the limbic system, CCK increases the release of beta-endorphin from the anterior pituitary, NPY is a powerful anxiolytic that regulates beta-endorphin and insulin, while VIP indirectly regulates the expression of TNF-alpha through the inhibition of interleukin-4 (IL-4).
authors.affiliation: Medical Research Unit, University of Wollongong, NSW, Australia.
authors.forename: R J
authors.initials: RJ
authors.lastname: Holden
authors.forename: I S
authors.initials: IS
authors.lastname: Pakula
mesh_terms: D000818:Animals; D000856:Anorexia Nervosa / Q000276:immunology* / Q000503:physiopathology; D001007:Anxiety / Q000276:immunology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D016207:Cytokines / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D015213:Neuroimmunomodulation; D009479:Neuropeptides / Q000502:physiology; D013312:Stress, Physiological / Q000276:immunology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D016207:Cytokines; D009479:Neuropeptides; D014409:Tumor Necrosis Factor-alpha