, 2000) or with failed quit attempts (Berlin et al., 2010), but not in those who remain abstinent for long period (Korhonen et al., 2011). This cannot be implied, though, from our findings as there are no data on quitting self-efficacy or failed quit attempts in NESDA. The former smokers in our study remained abstinent at an average of approximately twelve years (data not

shown) which might be the reason that their symptoms were comparable with never-smokers. However, it is still interesting that non-dependent smokers are not significantly different in CH5424802 cell line their symptoms from the non-smoking groups. Thus our findings suggest that smoking might be associated with the onset or the increasing severity of anxiety disorders only when smokers are nicotine-dependent. The worse outcome observed in nicotine-dependent smokers might be

due to the fact that chronic nicotine use might have an adverse effect on the brain and the neurotransmission systems. For example, nicotine use and anxiety or depression have both been linked to elevated dopamine (Fride and Weinstock, 1988 and Pontieri et al., 1996), low brain-derived neurotrophic factor Inhibitor Library solubility dmso (BDNF) levels (Kim et al., 2007 and Sen et al., 2008), and low Monoamine Oxidase (MAO) activity (Andersch and Hetta, 2001 and Fowler et al., 1996). Future investigations are needed on the impact of smoking or nicotine dependence on the dopamine, BDNF levels and MAO activity in relation to anxiety SB-3CT or aversive mood states in order to elucidate the mechanisms, and to help better

our understanding of the complex association. Regarding the notion of self-medication as motivator for smoking, our findings suggest that chronic and heavy nicotine use does not help to alleviate negative affect and may be even counterproductive. This may be used in educational programs for smokers who think that smoking helps them to control their mood states. Our findings also point to the importance of considering nicotine dependence symptoms in psychiatric patients in health prevention and intervention programs; thus more effective methods for managing depression and anxiety disorders should be developed. In psychiatric patients who smoke, a screening for nicotine dependence symptoms in medical settings would be useful to be implemented, and nicotine-dependent patients may be prioritized for smoking cessation programs. The infrastructure for the NESDA study (www.nesda.