Our aim with the discussion of these specific pathways was to provide a framework for future research that can be integrated with other theories of anxiety development, to hopefully lead to a holistic understanding of anxiety pathogenesis. Methods For this narrative review, we searched biomedical databases PubMed, Embase, and PsycInfo in mid-2012 using terms “anxiety”, Inhibitors,research,lifescience,medical “anxiety disorder”, “panic disorder”, “post traumatic stress disorder”, “obsessive

compulsive disorder”, “generalized anxiety disorder”, “social phobia”, “inflammation”, “immune”, “tobacco”, “cigarette”, “smoke”, “nicotine”, “oxidative stress”, “nitrogen stress”, “mitochondria”, “neurotrophin”, “neurogenesis”, and “psychiatry” in various combinations to identify relevant papers for the Inhibitors,research,lifescience,medical outlined sections. We did not limit the search by year of publication, but did limit to English language publications. We were deliberately inclusive in identifying relevant papers due to the scant availability of research in some areas. All bibliographies of identified papers were searched for further relevant information. Once acquired, studies were grouped into the following headings: clinical studies, structural brain changes and clinical correlates, neurotransmitter systems, inflammation and cell-mediated immune activation, oxidative

and nitrosative stress, mitochondrial function, NTs and neurogenesis, Inhibitors,research,lifescience,medical epigenetics and neurodevelopmental Inhibitors,research,lifescience,medical effects. Where possible, we presented literature pertaining to individual anxiety disorder states (e.g., panic disorder [PD], post traumatic stress disorder [PTSD], generalized anxiety disorder [GAD] etc.). Where this was not possible (e.g., in discussion of studies pertaining to psychological stress or anxiety symptom scores, or in animal studies), we have presented results relating to “anxiety” in general. Clinical Studies Cigarette Trametinib smoking as risk Inhibitors,research,lifescience,medical factor for anxiety disorders – epidemiological studies In addition to many studies

demonstrating a cross-sectional relationship between cigarette smoking and anxiety disorders, numerous population-based studies (Breslau and Klein 1999; Johnson et al. 2000; Isensee et al. 2003; Goodwin et al. 2005; Cuijpers et al. 2007; Chou et al. 2011) have demonstrated smoking as being prospectively associated with increased rates of anxiety disorders (see review Moylan et al. 2012a). Although most have utilized adult populations, some studies Sitaxentan have demonstrated adolescent smoking as being associated with increased rates of some anxiety disorders (Johnson et al. 2000; Goodwin et al. 2005). For example, in a study utilizing data from the Oregon Adolescent Depression Project, the odds ratio of expressing PD at age 24 when comparing baseline (age 14–18) daily smoking to nondaily smoking was 5.1 (95% CI 2.4–10.5), which remained significant after controlling for other anxiety disorders and parental risk factors.