ForewordIn

this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors’ commentary follows.StageA 20-year-old female college student presented with a 2-week history of fatigue, cough, sinus congestion, and rhinorrhea, followed by 2 days of vomiting, diarrhea, and abdominal pain. The patient’s initial symptoms began during her end-of-semester winter examination period; she knew many people who had been ill with similar symptoms, including fatigue and upper respiratory symptoms. Quisinostat mw The patient was recovering when she began to have nonbilious, nonbloody emesis and frequent, loose, nonbloody bowel movements. ResponseUpper respiratory tract symptoms, particularly

when they occur in the winter and involve a number of contacts, are suggestive of a community-acquired respiratory virus, such …”
“Recently, the inflammatory and neurodegenerative (I&ND) hypothesis of depression was formulated et al., 2009), i.e. the neurodegeneration and reduced neurogenesis that characterize depression are caused inflammation, cell-mediated immune activation and their long-term sequels. The aim of this paper is review the body of evidence that external stressors may induce (neuro)inflammation, neurodegeneration reduced neurogenesis; and that antidepressive treatments may impact on these selleck inhibitor pathways.

The chronic mild stress (CMS) and learned helplessness (LH) models show that depression-like behaviors accompanied by peripheral and central inflammation, neuronal cell damage, decreased neurogenesis and apoptosis in the hippocampus. External stress-induced depression-like behaviors are associated with a) increased interleukin-(IL)1 beta, tumor necrosis factor-alpha, IL-6, click here nuclear factor kappa B, cyclooxygenase-2, expression Toll-like receptors and lipid peroxidation; b) antineurogenic effects and reduced brain-derived neurotrophic factor (BDNF) levels;

and c) apoptosis with reduced levels of Bcl-2 and BAG1 (Bcl-2 associated athanogene 1), and increased levels of caspase-3. Stress-induced inflammation, e.g. increased IL-1 beta but not reduced neurogenesis, is sufficient to cause depression. Antidepressants a) reduce peripheral and central inflammatory pathways by decreasing IL-1 beta, TNF alpha and IL-6 levels; b) stimulate neuronal differentiation, synaptic plasticity, axonal growth and regeneration through stimulatory effects on the expression of different neurotrophic factors, e.g. trkB, the receptor for brain-derived neurotrophic factor; and c) attenuate apoptotic pathways by activating Bcl-2 and Bcl-xl proteins, and suppressing caspase-3.

It is concluded that external stressors may provoke depression-like behaviors through activation of inflammatory, oxidative, apoptotic and antineurogenic mechanisms.