2012). For example, patients with PD demonstrated higher

FA values in the left anterior and right posterior cingulate correlated with symptom severity (Han et al. 2008). Further, studies in patients with GAD demonstrated reduced FA in the uncinate fasciculus (Hettema et al. 2012) (connecting the amygdala and orbitofrontal cortex), a result also demonstrated in social phobia (SP) (Phan et al. 2009; Baur et al. 2011), and increased FA in the right postcentral gyrus (Zhang et al. 2011b). In PTSD, lowered FA has been found in areas including the left frontal gyrus, internal capsule, and midbrain (Kim et al. 2005; Schuff et al. 2011). Inhibitors,research,lifescience,medical Changes in integrity of white matter Microtubule Associated inhibitor pathways connecting fear areas, including the uncinate fasciculus and corpus callosum, have been associated with trait anxiety states (Kim and Whalen 2009; Baur et al. 2011; Westlye et al. Inhibitors,research,lifescience,medical 2011). We are aware of only one study assessing the effect of psychiatric disorders and smoking on white matter integrity. Zhang et al. (2010a), assessing patients with schizophrenia, demonstrated reductions in FA of the

Inhibitors,research,lifescience,medical left anterior thalamic radiation/anterior limb of the internal capsule that were both independent and additive in smokers and patients with schizophrenia, such that smokers with schizophrenia had the largest reductions Inhibitors,research,lifescience,medical in FA. No studies to our knowledge have yet been conducted in patients with anxiety disorders. In summary, gross and microstructural changes to key brain regions and white matter tracts are present in cigarette smokers and patients with anxiety disorders.

Changes to white matter microstructure in certain regions connecting fear response areas have been associated with trait anxiety states, and it is possible that cigarette smoke could negatively affect these pathways. Future Inhibitors,research,lifescience,medical research into these areas may provide important insights into anxiety pathogenesis. Neurotransmitter systems The importance of specific neurotransmitter systems has been extensively demonstrated in anxiety disorders, with current first-line pharmacological therapies interacting predominantly from with the serotonergic, noradrenergic, cannabinoid, cholinergic, and dopaminergic systems. In addition, some of these agents are also effective in enhancing smoking cessation (Jorenby et al. 1999), suggesting a plausible biological interaction between these systems and nicotine dependence. Many studies have demonstrated that nicotine and cigarette smoke affect diverse neurotransmitter systems. However, how these may predispose to increased anxiety is very complex, involving interaction between systems and differing effects of cigarette components. Much scientific work has explored the influence of nicotinic acetylcholine receptors (nAChRs) on brain function.