Working memory deficits predict short-term smoking resumption following brief abstinence

Abstract

As many as one-half of smokers relapse in the first week following a quit attempt, and subjective reports of cognitive deficits in early abstinence are associated with increased relapse risk. This study examined whether objective cognitive performance after 3 days of abstinence predicts smoking resumption in a 7-day simulated quit attempt. Sixty-seven treatment-seeking smokers received either varenicline or placebo (randomized double-blind) for 21 days. Following medication run-up (days 1–10), there was a 3-day mandatory (biochemically confirmed) abstinence period (days 11–13) during which working memory (Letter-N-Back Task) and sustained attention (Continuous Performance Task) were assessed (day 13). Participants were then exposed to a scheduled smoking lapse and instructed to try to remain abstinent for the next 7 days (days 15–21). Poorer cognitive performance (slower correct reaction time on Letter-N-Back task) during abstinence predicted more rapid smoking resumption among those receiving placebo (p = 0.038) but not among those receiving varenicline. These data lend further support for the growing recognition that cognitive deficits involving working memory are a core symptom of nicotine withdrawal and a potential target for the development of pharmacological and behavioral treatments.

Introduction

Following a quit attempt, smokers commonly report withdrawal-related cognitive symptoms (Hughes, 2007, Ward et al., 2001), and objective deficits in attention and working memory have been documented in human laboratory studies (Mendrek et al., 2006, Myers et al., 2008). Nicotine re-exposure following deprivation reverses these cognitive deficits in animals (Davis et al., 2005) and humans (Myers et al., 2008), supporting the hypothesis that relapse to smoking may occur as an attempt to ameliorate these deficits. Efficacious medications, such as varenicline, also reverse abstinence-induced cognitive deficits, suggesting that cognition may be a valuable target for the development of pharmacological and behavioral therapies (Lerman et al., 2007, Patterson et al., 2009, Raybuck et al., 2008).

Few studies have examined the relationship between withdrawal-related cognitive deficits and smoking relapse. In smokers with schizophrenia, poor performance on sustained attention (Culhane et al., 2008) and working memory tasks (Dolan et al., 2004) predicts relapse, with similar findings among depressed smokers (Kassel et al., 2007). Only one study has examined the role of cognitive deficits in relapse among healthy smokers (Rukstalis et al., 2005), showing that self-reported inattention predicts relapse.

This human laboratory study examined whether objective cognitive performance after 3–days of abstinence predicts resumption to smoking in a 7-day simulated quit attempt. We hypothesized that slower performance on working memory and sustained attention tasks during abstinence would predict faster smoking resumption among smokers treated with placebo. No such relationship was expected among smokers treated with varenicline, because varenicline attenuates abstinence-induced cognitive deficits (Patterson et al., 2009).