1999; Bob et al. 2010), increased TNF-α, IFN-γ, IL-1β, and decreased production of interleukin-8 (IL-8) and interleukin-2 (IL-2). More recently, increases in a number of proinflammatory cytokines and chemokines (IL-6, IL-1α, IL-1β, IL-8, monocyte chemotactic protein-1 [MCP-1], macrophage

inflammatory protein-1 α [MIP-1α], Inhibitors,research,lifescience,medical eotaxin, granulocyte macrophage CSF [GM-CSF], interferon-alpha [IFN-α]) were observed in patients with PD and PTSD (Hoge et al. 2009). A number of factors may help explain the above heterogeneous results, including differences between anxiety disorder subtypes, study design, and confounding factors. Despite these heterogeneous results, other insights suggest increased inflammation contributes to anxiety pathogenesis. For instance, Inhibitors,research,lifescience,medical cytokine-based selleck immunotherapy can lead to increased anxiety symptoms (Maes et al. 2001). Furthermore, depressive and anxiety symptoms induced by administration of cytokines are responsive to selective SSRIs (Gupta et al. 2006; de Knegt et al. 2011). We are not aware of any studies that have assessed the impact of cigarette smoking on inflammatory mediator expression in anxiety disorders. However, there is evidence that smoking and depression act synergistically to increase inflammation (Nunes et al. 2012). Inhibitors,research,lifescience,medical Further, in a study assessing cytokine

levels in the gingival crevicular fluid in patients with periodontal disease, levels of inflammatory cytokines IL-6 and IL-8 were both positively correlated with increasing psychological stress, as measured by the Modified and Perceived Stress Scale (Linn 1986), and cigarette smoking

Inhibitors,research,lifescience,medical (Giannopoulou et al. 2003). Oxidative and nitrosative stress Free radicals are by-products of oxidative Inhibitors,research,lifescience,medical phosphorylation that, at low or moderate concentrations, participate in normal cellular processes such as signaling pathways, mitosis, apoptosis, and responses to injury or infection (Valko et al. 2007). However, damage can occur to cellular components, including proteins, nucleic acid, carbohydrates, and lipids when levels of oxidative free however radicals increase beyond the antioxidant capacity of cells. Increases in free radical concentrations can occur through both increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and/or decreased expression of antioxidants (Hovatta et al. 2010). Damage to these cellular components can alter the structure and function of membrane fatty acids and proteins, and alter or damage DNA and mitochondrial function leading to cell death (Maes et al. 2011b). Increased plasma markers of O&NS have been repeatedly demonstrated in anxiety-disordered populations and animal models of anxiety (for review see Hovatta et al. 2010). In addition, increased hippocampal oxidative stress is anxiogenic (de Oliveira et al. 2007).