Nicotine withdrawal is associated with deficits in neurocognitive function including sustained attention, working memory, and response inhibition. Several convergent lines of evidence suggest that these deficits may represent a core dependence phenotype and a target for treatment development efforts. A better understanding of the mechanisms underlying withdrawal-related cognitive deficits may lead to improve nicotine dependence treatment. We begin with an overview of the neurocognitive effects of withdrawal in rodent and human models, followed by discussion of the neurobehavioral mechanisms that are thought to underlie these effects. We then review individual differences in withdrawal-related neurocognitive effects including genetics, gender, and psychiatric comorbidity. We conclude with a discussion of the implications of this research for developing improved therapies, both pharmacotherapy and behavioral treatments, that target cognitive symptoms of nicotine withdrawal.
[Show abstract][Hide abstract] ABSTRACT: The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype x drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment.Neuropsychopharmacology accepted article preview online, 24 June 2013; doi:10.1038/npp.2013.152.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 06/2013; 38(12). DOI:10.1038/npp.2013.152 · 7.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the early time course of smoking withdrawal effects has been characterized, the clinical significance of early withdrawal symptoms and their predictors are unknown. This study evaluated the relationships of early smoking withdrawal effects with quit attempt outcomes and the rate of nicotine metabolism.
Eleven treatment-seeking smokers abstained from smoking for 4hr in the laboratory, before a quit attempt. Withdrawal measures included heart rate, sustained attention, and self-report. Following baseline assessment, withdrawal measures were administered every 30min. At the conclusion of the 4-hr early withdrawal session, participants received a brief smoking cessation intervention and then returned 1 week and 12 weeks later for outcome assessments that included biochemically confirmed smoking abstinence, cigarettes smoked in the past 24hr, and self-reported withdrawal symptoms. The rate of nicotine metabolism was estimated at intake using the nicotine metabolite ratio (trans-3'-hydroxycotinine/cotinine) measured in saliva.
Greater self-reported negative affect and concentration difficulty during early withdrawal, most notably anxiety, were related with poorer quit attempt outcomes. There was some indication that although a faster increase in craving and greater hunger during early withdrawal were associated with more favorable outcomes, a greater decrease in heart rate during this time was associated with poorer outcomes. Faster nicotine metabolism was related to a faster increase in anxiety but a slower increase in craving during early withdrawal.
These findings lend support to the clinical significance of early smoking withdrawal effects. The rate of nicotine metabolism may be a useful predictor of early withdrawal symptoms.
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