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Not all smokers are alike: the hidden cost of sustained attention during nicotine abstinence.

ABSTRACT: Nicotine Withdrawal Syndrome (NWS)-associated cognitive deficits are notably heterogeneous, suggesting underlying endophenotypic variance. However, parsing this variance in smokers has remained challenging. In this study, we identified smoker subgroups based on response accuracy during a Parametric Flanker Task (PFT) and then characterized distinct neuroimaging endophenotypes using a nicotine state manipulation. Smokers completed the PFT in two fMRI sessions (nicotine sated, abstinent). Based on response accuracy in the stressful, high cognitive demand PFT condition, smokers split into high (HTP, n = 21) and low task performer (LTP, n = 24) subgroups. Behaviorally, HTPs showed greater response accuracy (88.68% ± 5.19 SD) vs. LTPs (51.04% ± 4.72 SD), independent of nicotine state, and greater vulnerability to abstinence-induced errors of omission (EOm, p = 0.01). Neurobiologically, HTPs showed greater BOLD responses in attentional control brain regions, including bilateral insula, dorsal ACC, and frontoparietal Cx for the [correct responses (-) errors of commission] PFT contrast in both states. A whole-brain functional connectivity (FC) analysis with these subgroup-derived regions as seeds identified two circuits: Precentral Cx↔Insula and Insula↔Occipital Cx, with abstinence-induced FC strength increases seen only in HTPs. Finally, abstinence-induced FC and behavior (EOm) differences were positively correlated for HTPs in a Precentral Cx↔Orbitofrontal cortical circuit. In sum, only the HTP subgroup demonstrated sustained attention deficits following 48-hr nicotine abstinence, a stressor in dependent smokers. Unpacking underlying smoker heterogeneity with this 'dual (task and abstinence) stressor' approach revealed discrete smoker subgroups with differential attentional deficits to withdrawal that could be novel pharmacological/behavioral targets for therapeutic interventions to improve cessation outcomes.

SUBMITTER: Deshpande HU

PROVIDER: S-EPMC9283548 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionAlthough exogenous progesterone may hold promise as a treatment for nicotine use disorders, it is unclear whether it is similarly effective in males and females. This study examined the effects of progesterone on nicotine use disorder comprehensively using behavioral, psychological, and neural measures in male and female smokers exposed to brief abstinence.Aims and methodsThirty-three male and 33 female non-treatment-seeking smokers participated in a double-blind, randomized, placebo-controlled crossover study of 200 mg of progesterone or placebo daily over a four-day abstinence period. Smoking behavior and subjective effects of nicotine were assessed at baseline and after final drug administration. Nicotine withdrawal, smoking urges, mood states, and neural response to smoking cues were measured at baseline, after the first drug administration, and after the final drug administration.ResultsNo main effect of drug (progesterone vs. placebo) emerged for any outcome. Significant sex by drug interactions emerged for nicotine withdrawal (p = .020), perceived strength of nicotine (p = .040), and perceived bad effects of nicotine (p = .029). Males receiving progesterone reported worse nicotine withdrawal (p = .046) and a trend towards decreased bad effects of nicotine (p = .070). Males on progesterone also reported greater tension and anxiety relative to placebo (p = .021). Females on progesterone perceived nicotine's effects as being stronger relative to placebo (p = .046).ConclusionsProgesterone causes sex-dependent effects on smoking-related outcomes during brief abstinence. Specifically, progesterone in males may increase rather than decrease nicotine withdrawal and negative affect during abstinence, potentially hindering efforts to quit smoking.ImplicationsIn male and female smokers undergoing a brief period of abstinence, we examined the effects of progesterone on smoking outcomes. While progesterone had limited effects in female smokers, in males, it worsened nicotine withdrawal and negative affect. Our findings emphasize the importance of analyzing sex differences in future studies examining progesterone as a potential treatment and suggest that progesterone in males could potentially exacerbate aspects of nicotine dependence.Clinicaltrials.gov registrationNCT01954966. https://clinicaltrials.gov/ct2/show/NCT01954966.

Project description:IntroductionPsychological, physiological and social factors play an important role in the initiation, persistence, dependence and relapse of smoking behaviors, and coping style and smoking abstinence self-efficacy can all affect nicotine dependence.MethodsA cross-sectional sample of 568 quitters from 19 communities in Beijing in 2019 was surveyed. Demographic information and psychological characteristics of smokers were collected by an interview questionnaire, and psychological traits scales including the Smoking Abstinence Self-Efficacy (SASE) and the Trait Coping Style Questionnaire (TCSQ). We compared differences in psychological traits across demographic information and explored the relationship between nicotine dependence and coping styles and self-efficacy in refusing to smoke.ResultsSignificant differences were identified in self-efficacy in refusing to smoke and across dimensions among quitters by gender, job type, education level, and monthly income level (all p<0.05). Males had lower self-efficacy in the habitual/addictive context than females; retirees had better overall self-efficacy and self-efficacy in the negative/emotional context than business service workers and professionals; and high-educated, high-income quitters had lower self-efficacy in the negative/emotional context. There are significant differences in positive coping styles among quitters of different ages, levels of education, and types of work (all p<0.05). The results further showed that the underage population, highly educated population, and practitioners other than those in retirement, are less likely to use positive coping styles. Interventional effects analysis showed that a higher sense of self-efficacy in addictive contexts can counteract some of the negative coping styles that induce smoking.ConclusionsSelf-efficacy played an indirect mediating role between negative coping style and nicotine dependence; individuals who used more negative coping styles were more likely to engage in smoking and therefore were more nicotine dependent. Hence, it is necessary to reduce the use of negative coping strategies and improve the self-efficacy of smoking abstinence in the face of addiction.

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Not all smokers are alike: the hidden cost of sustained attention during nicotine abstinence.

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