, 2005; Williams et al., 2010). Our studies have also found higher levels of nicotine boost in SS (28 ng/ml) as well as a those higher total dose of nicotine from smoking a single cigarette than CON (Williams et al., 2010). Since individuals with schizophrenia experience more than twenty years of reduced life expectancy largely due to the effects of smoking (Kelly et al., 2011; Miller, Paschall, & Svendsen, 2006), it is a priority to improve on methods to help these patients quit. A barrier to achieving this goal is that it is not yet clear why people with schizophrenia smoke differently (e.g., rapid puffing and higher nicotine intake). One hypothesis is that SS smoke more due to alterations in brain dopaminergic systems that increase the sensitivity to positive reinforcement from addicting substances (Chambers, Krystal, & Self, 2001).

This may contribute to their excessive use of not only nicotine but also caffeine and other drugs (Gandhi, Williams, Menza, Galazyn, & Benowitz, 2010). Animal models of schizophrenia demonstrate addiction vulnerability (Chambers & Taylor 2004), and it has been argued that substance use is a core symptom of schizophrenia (Chambers et al., 2001). Higher nicotine levels from rapid puffing and shorter time between puffs may increase addictive potential and reinforcement value, possibly explaining why SS have reduced success in smoking cessation. SS report higher levels of negative affect (NA), less positive affect, a greater anticipation that smoking will relieve NA (QSU Factor 2; Williams et al., 2011).

QSU Factor 2 (anticipation that smoking will relieve negative affect) and PANAS negative scores in this study were associated with rapid smoking. This means that smoking more intensely (i.e., more frequent puffing and reduced IPI) may be in response to having less ability to tolerate NA whether from withdrawal or other reasons. In combination, our findings of higher nicotine intake and rapid puffing in SS may reflect an ��urgency�� to smoke in these individuals that is still poorly understood. Lack of aversive effects is interesting as it relates to a newly described acetylcholine receptor alpha5 subunit single nucleotide polymorphism (SNP). This SNP is associated with smoking quantity and severity (Berrettini et al., 2008) including a lack of aversive effects to high dose nicotine (Fowler, Lu, Johnson, Marks, & Kenny, 2011).

Animal models similarly show that deletion of alpha5 subunits enhances nicotine self-administration, supporting their role in nicotine intake mechanisms (Fowler, Arends, & Kenny, 2008). Alpha5 receptors are heavily concentrated Brefeldin_A in the medial habenula, which is being investigated as a major regulatory center for nicotine consumption, reward, and aversion (Frahm et al., 2011), in addition to its potential role in psychosis and psychiatric illness.