Background Although the amygdala and insula are regarded as critical neural substrates perpetuating cigarette smoking, little is known about their circuit-level interactions with interconnected regions during nicotine withdrawal or following pharmacotherapy administration. To elucidate neurocircuitry associated with early smoking abstinence, we examined the impact of varenicline and nicotine, two modestly efficacious pharmacological cessation aids, on amygdala- and insula-centered circuits using resting-state functional connectivity (rsFC). Methods In a fMRI study employing a two-drug, placebo-controlled design, 24 overnight-abstinent smokers and 20 nonsmokers underwent ~17 days of varenicline and placebo pill administration and were scanned, on different days under each condition, wearing a transdermal nicotine or placebo patch. We examined the impact of varenicline and nicotine (both alone and in combination) on amygdala- and insula-centered rsFC using seed-based assessments. Results Beginning with a functionally-defined amygdala seed, we observed that rsFC strength in an amygdala-insula circuit was down-regulated by varenicline and nicotine in abstinent smokers. Using this identified insula region as a new seed, both drugs similarly decreased rsFC between the insula and constituents of the canonical default-mode network (DMN: posterior cingulate cortex, ventro/dorsomedial prefrontal cortex, parahippocampus). Drug-induced rsFC modulations were critically linked with nicotine withdrawal as similar effects were not detected in nonsmokers. Conclusions These results suggest that nicotine withdrawal is associated with elevated amygdala-insula and insula-DMN interactions. As these potentiated interactions were down-regulated by two pharmacotherapies, this effect may be a characteristic shared by pharmacological agents promoting smoking cessation. Decreased rsFC in these circuits may contribute to amelioration of subjective withdrawal symptoms. (http://www.clinicaltrials.gov, ID:NCT00830739).

Rationale Alexithymia is a personality trait characterized by difficulty indentifying and describing subjective emotional experiences. Decreased aptitude in the perception, evaluation, and communication of affectively laden mental states has been associated with reduced emotion regulation, more severe drug craving in addicts, and structural/functional alterations in insula and anterior cingulate cortex (ACC). The insula and ACC represent sites of convergence between the putative neural substrates of alexithymia and those perpetuating cigarette smoking. Objectives We examined the interrelations between alexithymia, tobacco craving, and insula/ACC neurocircuitry using resting-state functional connectivity (rsFC). Methods Overnight-deprived smokers (n=24) and non-smokers (n=20) completed six neuroimaging assessments on different days both in the absence of, and following, varenicline and/or nicotine administration. In this secondary analysis of data from a larger study, we assessed trait alexithymia and state tobacco craving using self-reports and examined the rsFC of bilateral insular subregions (anterior, middle, posterior) and dorsal ACC. Results Higher alexithymia in smokers predicted reduced rsFC strength between the right anterior insula (aI) and ventromedial prefrontal cortex (vmPFC). Higher alexithymia also predicted more severe tobacco craving during nicotine withdrawal. Critically, the identified aI–vmPFC circuit fully mediated this alexithymia–craving relation. That is, elevated alexithymia predicted decreased aI–vmPFC rsFC and, in turn, decreased aI–vmPFC rsFC predicted increased craving during withdrawal. A moderated mediation analysis indicated that this aI–vmPFC mediational effect was not observed following drug administration. Conclusions These results suggest that a weakened right aI–vmPFC functional circuit confers increased liability for tobacco craving during smoking abstinence. Individual differences in alexithymia and/or aI–vmPFC functional coupling may be relevant factors for smoking cessation success.

Objective The purpose of this study is to understand how cancer risk behaviors cluster in U.S. college students and vary by race and ethnicity. Methods Using the fall 2010 wave of the National College Health Assessment (NCHA), we conducted a latent class analysis (LCA) to evaluate the clustering of cancer risk behaviors/conditions: Tobacco use, physical inactivity, unhealthy diet, alcohol binge drinking, and overweight/obesity. The identified clusters were then examined separately by students’ self-reported race and ethnicity. Results Among 30,093 college students surveyed, results show a high prevalence of unhealthy diet as defined by insufficient fruit and vegetable intake (>95%) and physical inactivity (>60%). The LCA identified behavioral clustering for the entire sample and distinct clustering among Black and American Indian students. Conclusions Cancer risk behaviors/conditions appear to cluster among college students differentially by race. Understanding how risk behaviors cluster in young adults can lend insight to racial disparities in cancer through adulthood. Health behavior interventions focused on modifying multiple risk behaviors and tailored to students’ racial group could potentially have a much larger effect on cancer prevention than those targeting any single behavior.

Injection drug use plays a critical role in the spread of HIV/AIDS, with an estimated 19,000 drug users infected each year. Counselling and testing services can be an important gateway for engaging HIV-infected individuals into medical care and can positively influence the preventive behaviours of IDUs. This study seeks to document and understand the complexity and range of motivations and deterrents to HIV testing among IDUs. Participants were recruited using a convenience sampling method. Interviews consisted of a qualitative guide and a quantitative survey to collect HIV testing histories, sex and drug risk behaviours, and demographic information. Interview data was coded and content analyzed to identify emerging themes and clarify the processes that drug users employ in deciding whether or not to test. Sixty-six drug users were interviewed. The sample reported a median of four lifetime HIV tests. Participants described a range of motivating and deterring factors to HIV testing across personal, interpersonal and structural categories. Drug users' decision to test is influenced by a complex network of factors. Better understanding of these motivators and deterrents can help providers develop a more holistic approach to targeting this high-risk population for HIV prevention efforts.

This study demonstrated that data from a production clinical decision support system can be used to build an accurate machine learning model to predict obesity in children after age two.

Hyperactive amygdala functioning may underlie emotional dysregulation during smoking abstinence and represents one neurobiological target for pharmacological cessation aids. Available pharmacotherapies (e.g., nicotine replacement and varenicline) aid only a subset of individuals with smoking cessation and therefore elucidating the neurobiological impact of these medications is critical to expedite improved interventions. In a fMRI study employing a within-subject, double-blind, placebo-controlled design, we assessed task performance and amygdala functioning during an emotional face matching paradigm following administration of nicotine and varenicline to 24 abstinent smokers and 20 nonsmokers. All participants underwent ~17 days of varenicline and placebo pill administration and were scanned, on different days under each condition, wearing a transdermal nicotine or placebo patch. During the amygdala reactivity paradigm, nicotinic acetylcholine receptor (nAChR) stimulation by nicotine and varenicline decreased reaction time (RT) in abstinent smokers but not in nonsmokers. When considering all smokers as a single homogenous group, no drug-induced effects on amygdala reactivity were detected. However, in an exploratory analysis we parsed participants into subgroups according to individual differences in the propensity to demonstrate stable performance augmentation following nAChR stimulation (stable RT-improvers [SI] vs. variable RT-improvers [VI]). Using this exploratory approach, drugs appeared to modulate amygdala reactivity in only one smoker subgroup but not in either nonsmoker subgroup. Specifically, in the SI-smoker cohort abstinence-induced elevated amygdala reactivity was down-regulated by nAChR stimulation. In contrast, varenicline and nicotine did not modulate amygdala functioning in the VI-smoker cohort who displayed moderate levels of amygdala reactivity in the absence of drug administration. These results suggest that pharmacotherapies most robustly dampened amygdala functioning in smokers appearing susceptible to abstinence-induced effects. Such findings provide a step towards fractionating the smoker phenotype by discrete neurobiological characteristics.

Based on this review, the authors address clinical implications, particularly incorporating psychological treatment for sexual problems in comprehensive cancer care, and provide recommendations for further study.

The benefits of varenicline for treating tobacco dependence among cancer patients may depend upon boosting adherence by addressing early signs of depression and reducing the reinforcing dimensions of cigarettes.