 The prevalence of smoking is unusually high among patients with SCZ. In light of the negative health, economic, and social consequences of smoking, treatment efforts in this area are imperative. Such efforts rest, in part, on an improved understanding of the underlying causes of smoking within this unique population. For example, several lines of research have indicated that smoking improves specific SCZ-related symptoms i.e., negative psychotic symptoms, negative affect, cognitive deficits and that patients may smoke to self-medicate with nicotine. However, the mechanisms underlying this effect are unknown. The current proposal posits that improved NI may be one such mechanism. More specifically, NI is conceived as a mediator of the relationship between smoking and symptom improvement. Also, given its proposed mechanistic nature, we believe that nicotine-related changes in NI may predict quitreduction andor relapse rates following a smoking cessation program. Additionally, variants of CHRNA7 likely represent the genetic underpinnings of decreased NI, vulnerability to smoking, and smoking treatment resistance among patients with SCZ. These hypotheses are supported by previous experiments that suggest: 1 patients with SCZ have decreased NI Adler et al., 1998; 2 nicotine administration via its effects on the alpha-7-nicotinic receptor, which, in turn activates GABAergic interneurons enhances NI in these patients Adler et al., 1998; 3 genetic variation in the alpha-7-nicotinic receptor increases risk for smoking among patients with SCZ Leonard et al., 1996; and, 4 higher levels of NI are associated with fewer negative symptoms, less negative affect, and better cognition Yee et al., 1998. However, these studies have been hampered by several methodological and conceptual shortcomings including small sample sizes, the presence of confounding variables e.g., the effects of nicotine withdrawal, and limited testing of relevant symptom domains. Furthermore, previous studies have examined only isolated aspects of the proposed model, leaving many of the central relationships between variables untested and speculative. The current proposal seeks to rectify these methodological issues within the context of a multidisciplinary scientific team. Globally, its objectives are twofold. First, to replicate and extend previous findings that nicotine causes symptom attenuation. Second to investigate the underlying neurophysiological and genetic mechanisms of these effects. The specific objectives and hypotheses addressed in this study are as follows: 