Tumor necrosis factor-α: is there a continuum of liability between stress, anxiety states and anorexia nervosa?

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-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and downregulation of interferon-γ (IFN-γ). Sustained elevation of IL-1β and TNF-α dysregulates both somatostatin and insulin secretion, the latter of which influences regional cerebral blood flow (rCBF) and brain energy metabolism. In addition, IL-1β and TNF-α influence the expression of certain crucial neuropeptides, which are known to be associated with anxiety states and anorexia nervosa. These neuropeptides include: β-endorphin, cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). β-endorphin effects glucose metabolism in the limbic system, CCK increases the release of β-endorphin from the anterior pituitary, NPY is a powerful anxiolytic that regulates β-endorphin and insulin, while VIP indirectly regulates the expression of TNF-α through the inhibition of interleukin-4 (IL-4).