Negative affective states and cognitive impairments in nicotine dependence

Abstract

Smokers have substantial individual differences in quit success in response to current treatments for nicotine dependence. This observation may suggest that different underlying motivations for continued tobacco use across individuals and nicotine cessation may require different treatments in different individuals. Although most animal models of nicotine dependence emphasize the positive reinforcing effects of nicotine as the major motivational force behind nicotine use, smokers generally report that other consequences of nicotine use, including the ability of nicotine to alleviate negative affective states or cognitive impairments, as reasons for continued smoking. These states could result from nicotine withdrawal, but also may be associated with premorbid differences in affective and/or cognitive function. Effects of nicotine on cognition and affect may alleviate these impairments regardless of their premorbid or postmorbid origin (e.g., before or after the development of nicotine dependence). The ability of nicotine to alleviate these symptoms would thus negatively reinforce behavior, and thus maintain subsequent nicotine use, contributing to the initiation of smoking, the progression to dependence and relapse during quit attempts. The human and animal studies reviewed here support the idea that self-medication for pre-morbid and withdrawal-induced impairments may be more important factors in nicotine addiction and relapse than has been previously appreciated in preclinical research into nicotine dependence. Given the diverse beneficial effects of nicotine under these conditions, individuals might smoke for quite different reasons. This review suggests that inter-individual differences in the diverse effects of nicotine associated with self-medication and negative reinforcement are an important consideration in studies attempting to understand the causes of nicotine addiction, as well as in the development of effective, individualized nicotine cessation treatments.

Keywords: Cognitive impairment; Negative affect; Negative reinforcement; Nicotine.

Figure 1. Possible contribution to nicotine dependence and continued use

Although a psychiatric diagnosis is not a pre-requisite for nicotine dependence, such a diagnosis greatly increases the likelihood of dependence. Natural tendencies (sub-clinical behaviors) tending toward a) negative affective states, e.g., lower reward processing capabilities, or b) cognitive deficits, e.g., inattention or impulsivity, could contribute toward initial nicotine use given nicotine-induced improvements in these behaviors in non-smokers. Once dependent however, the more pronounced negative reinforcement resulting from alleviation of nicotine withdrawal (exacerbating natural affective or cognitive impairments) likely strongly contributes to failed quite attempts (relapse). The mechanism(s) underlying the acquisition of nicotine dependence based upon positive reinforcement of nicotine intake likely differ from those underlying withdrawal-induced impact on affect or cognition (negative reinforcement of nicotine intake), suggesting that treatments to prevent relapse should be developed to counter negative reinforcement mechanisms. Withdrawal-induced effects on specific affective or cognitive domains often vary by individual and treatments developed to enhance quit attempts could be tailored to those domains.

Figure 2. Theoretical model of the opponent-process theory of smoking and withdrawal-induced relapse

Initiation of smoking likely produces cognitive benefits which dissipate over time with chronic use. Upon withdrawal, cognitive performance drops. For some, performance may not drop too far and eventually their performance normalizes again before a relapse incident (blue). In some individuals, cognitive performance may drop to intolerable levels and so they relapse and start smoking again (relapse, shown in green). Developing a treatment that could predate nicotine withdrawal however, to minimize withdrawal-induced deficits in cognition, would greatly enhance the likelihood of successfully quitting (red).