Impact of vitamin C supplementation on placental DNA methylation changes related to maternal smoking: association with gene expression and respiratory outcomes.

BACKGROUND: Maternal smoking during pregnancy (MSDP) affects development of multiple organ systems including the placenta, lung, brain, and vasculature. In particular, children exposed to MSDP show lifelong deficits in pulmonary function and increased risk of asthma and wheeze. Our laboratory has previously shown that vitamin C supplementation during pregnancy prevents some of the adverse effects of MSDP on offspring respiratory outcomes. Epigenetic modifications, including DNA methylation (DNAm), are a likely link between in utero exposures and adverse health outcomes, and MSDP has previously been associated with DNAm changes in blood, placenta, and buccal epithelium. Analysis of placental DNAm may reveal critical targets of MSDP and vitamin C relevant to respiratory health outcomes. RESULTS: DNAm was measured in placentas obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (37 supplemented with vitamin C, 35 with placebo) and 24 never-smokers for reference. Methylation at one CpG, cg20790161, reached Bonferroni significance and was hypomethylated in vitamin C supplemented smokers versus placebo. Analysis of spatially related CpGs identified 93 candidate differentially methylated regions (DMRs) between treatment groups, including loci known to be associated with lung function, oxidative stress, fetal development and growth, and angiogenesis. Overlap of nominally significant differentially methylated CpGs (DMCs) in never-smokers versus placebo with nominally significant DMCs in vitamin C versus placebo identified 9059 candidate "restored CpGs" for association with placental transcript expression and respiratory outcomes. Methylation at 274 restored candidate CpG sites was associated with expression of 259 genes (FDR < 0.05). We further identified candidate CpGs associated with infant lung function (34 CpGs) and composite wheeze (1 CpG) at 12 months of age (FDR < 0.05). Increased methylation in the DIP2C, APOH/PRKCA, and additional candidate gene regions was associated with improved lung function and decreased wheeze in offspring of vitamin C-treated smokers. CONCLUSIONS: Vitamin C supplementation to pregnant smokers ameliorates changes associated with maternal smoking in placental DNA methylation and gene expression in pathways potentially linked to improved placental function and offspring respiratory health. Further work is necessary to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes of offspring exposed to MSDP. Clinical trial registration ClinicalTrials.gov, NCT01723696. Registered November 6, 2012. https://clinicaltrials.gov/ct2/show/record/NCT01723696 .

Blood pressure-lowering effect of repeated Waon therapy in non-smokers with hypertension.

ABSTRACT: Waon therapy (WT) has been used as a thermal therapy in chronic heart failure patients. However, its effect in patients with hypertension is unclear. This study aimed to reveal the hypotensive effect of WT in patients with hypertension. WT was performed on 31 patients with hypertension (63.9 ±â€Š11.9 years, male: 17) on standard hypertension treatment focusing on lifestyle modification and medication. Systolic and diastolic blood pressures were measured before and after WT using an upper arm automated sphygmomanometer. We investigated the effect of single and repeated (1 time/d, >5 times) WT sessions on blood pressure and further compared its effect between current smoking (n = 11, 55.4 ±â€Š6.4 years, 8.5 ±â€Š2.4 times) and non-smoking (n = 11, 66.9 ±â€Š8.5 years, 12.2 ±â€Š5.9 times) groups. A total of 370 sessions of WT were conducted. Systolic and diastolic blood pressures significantly decreased after a single WT session (systolic blood pressure: 118.5 ±â€Š10.1 to 115.1 ±â€Š9.0 mm Hg, P < .001; diastolic blood pressure: 70.5 ±â€Š6.4 to 65.9 ±â€Š5.3 mm Hg, P < .001). The blood pressure decrease following repeated WT was not significant when all participants were considered (systolic blood pressure: 122.3 ±â€Š15.2 to 116.9 ±â€Š19.6 mm Hg; diastolic blood pressure: 73.8 ±â€Š16.7 to 68.2 ±â€Š13.2 mm Hg); however, it was significant in the non-smoking group (systolic blood pressure: 124.2 ±â€Š11.3 to 108.8 ±â€Š13.4 mm Hg, P < .001; diastolic blood pressure: 73.6 ±â€Š4.9 to 62.1 ±â€Š7.6 mm Hg, P < .001). Repeated WT (at least 5 sessions) decreased blood pressure in patients with hypertension, especially in non-smokers. WT is a simple method to reduce blood pressure in non-smoking patients with hypertension.

Factors Contributing to Vitamin D Status at Hospital Admission for Pulmonary Exacerbation in Adults With Cystic Fibrosis.

BACKGROUND: Individuals with cystic fibrosis (CF) have difficulty maintaining optimal vitamin D status due to pancreatic insufficiency-induced malabsorption, inadequate sunlight exposure, and poor intake of vitamin D containing foods. Vitamin D deficiency may increase the risk of pulmonary exacerbations of CF. The objective of this study was to assess factors impacting vitamin D status in patients with CF recently hospitalized for a pulmonary exacerbation of CF. METHODS: This was a pre-planned analysis of vitamin D intake in patients enrolled in a multi-center, double-blind, randomized controlled study examining vitamin D therapy for pulmonary exacerbation of CF. Demographic information, responses from a habitual sun exposure questionnaire and food frequency questionnaire, and vitamin D supplement usage were queried and compared to serum 25-hydroxyvitamin D (25(OH)D) concentrations. RESULTS: A total of 48 subjects were included in this analysis. Subjects were taking approximately 1,200 IU of vitamin D daily. Reported vitamin D intake, age, race, employment, and education were not significantly associated with vitamin D status in this population. However, smoking status, sunlight exposure in the last 3 years, and skin type (in the bivariate model) were all significantly associated with vitamin D status (all p<0.05). CONCLUSIONS: Sunlight exposure was the most predictive determinant of vitamin D status in patients with CF prior to pulmonary exacerbation. Subjects reported vitamin D intake below the recommended amounts. The role and mode of optimizing vitamin D status prior to a pulmonary exacerbation needs further investigation.

Randomized controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics.

BACKGROUND: Smoking worsens underlying asthma inflammation and also induces resistance to inhaled corticosteroids (ICS). Small airways dysfunction measured by impulse oscillometry (IOS) is associated with worse control. OBJECTIVES: We investigated the effects on small airways of adding long-acting beta-agonist (LABA) alone or with long-acting muscarinic antagonist (LAMA) to ICS in asthmatic smokers. METHODS: Sixteen current smokers were enrolled: mean age 44 year, FEV1 84%, FEF25-75 47%, R5 158%, ACQ 1.69, 20 pack year . Patients were converted to a reference ICS as HFA-BDP during initial run-in at median dose of 800 µg/day. Open label olodaterol 5 µg od (OLO) or olodaterol 5 µg/tiotropium 5 µg od (OLO/TIO) was added to HFA-BDP for median duration of 3 weeks in a randomized cross over design, including run-in and washout periods on HFA-BDP. IOS and spirometry were measured after each treatment (BDP/OLO/TIO or BDP/OLO) and at baseline after run-in and washout (BDP). RESULTS: After chronic dosing, IOS outcomes at trough except for R20 were all significantly improved with OLO/TIO compared to OLO. For the primary end-point of total airway resistance (as R5), the mean difference (95%CI) at trough was 0.06 (0.015-0.10) kPa/l/s, peripheral airways resistance (as R5-R20) 0.03 (0.003-0.06) kPa/l/s, peripheral lung reactance area (as AX) 0.38 (0.08-0.68) kPa/l and resonant frequency (as RF) 2.28 (0.45-4.12) Hz. FEF25-75 at trough was also better with OLO/TIO vs TIO: 0.93 (0.86 - 0.95) l/s while FEV1 was not different. CONCLUSIONS: ICS/LABA/LAMA was superior to ICS/LABA on trough small airway outcomes in asthma patients who smoke.

The effects of mindfulness-based yogic breathing on craving, affect, and smoking behavior.

Breathing practices are often incorporated into treatments for tobacco dependence, but there is little direct research testing the efficacy of breathing practices. This study examined the effects of a mindfulness-based yogic breathing (MB) intervention versus active treatment (cognitive strategy [CS]) and no-treatment (NT) control groups on craving, affect, withdrawal, and smoking behavior. Smokers (N = 60; 50% female; 83% African American) were randomized to receive 20 min of MB, CS, or NT. Participants completed self-report measures before and after the manipulation and then took part in a 50-min smoking choice procedure. Afterward, participants were advised to use the techniques they learned and self-monitor smoking for 24 hr. They received 3 reminder text messages and returned to the lab the following day. MB and CS were more effective than NT in decreasing craving to smoke and perceived nicotine withdrawal. MB, but not CS, was more effective than NT in reducing negative affect. MB reduced the risk of smoking by more than twofold relative to both CS and NT during the smoking choice procedure. Participants in the MB condition smoked fewer cigarettes than those in the CS and NT conditions in the 24 hr following the manipulation. There were no differential effects of the manipulations on state mindfulness or positive affect. Mindful yogic breathing appears to be particularly effective in alleviating the acute negative effects of smoking abstinence and decreasing smoking behavior. Mindful breathing techniques are safe, simple, and cost-effective strategies that deserve additional research attention, especially among underserved populations of smokers. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Laboratory test based assessment of WHO alcohol risk drinking levels.

Low-risk thresholds for alcohol use differ across various national guidelines. To assess the novel WHO risk drinking levels in light of alcohol-sensitive common laboratory tests, we analysed biomarkers of liver status, inflammation and lipid profiles from a population-based survey of individuals classified to abstainers and different WHO risk drinking levels defined in terms of mean alcohol consumption per day. The study included 22,327 participants aged 25-74 years from the National FINRISK Study. Data on alcohol use, health status, diet, body weight and lifestyle (smoking, coffee consumption and physical activity) were recorded from structured interviews. Alcohol data from self-reports covering the past 12 months were used to categorize the participants into subgroups of abstainers and WHO risk drinking categories representing low, moderate, high and very high risk drinkers. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Alcohol risk category was roughly linearly related with the occurrence of elevated values for GGT, ALT and CRP. Alcohol drinking also significantly influenced the incidence of abnormalities in serum lipids. Significantly higher odds for abnormal GGT, ALT and altered lipid profiles remained in alcohol drinkers even after adjustment for age, waist circumference, physical inactivity, smoking and coffee consumption. A more systematic use of laboratory tests during treatment of individuals classified to WHO risk drinking categories may improve the assessment of alcohol-related health risks. Follow-ups of biomarker responses may also prove to be useful in health interventions aimed at reducing alcohol consumption.

Lifestyle behavior patterns and mortality among adults in the NHANES 1988-1994 population: A latent profile analysis.

Evidence suggests interdependent associations of individual modifiable behaviors with health outcomes. However, such interrelations have not been accounted for in previous behavior-outcome associations. We conducted latent profile analysis (LPA) on self-reported levels of alcohol consumption, restaurant dining, vitamin/mineral supplement use, physical activity (PA) and smoke exposure (first- and second-hand smoke) separately for smokers (N = 4530) and non-smokers (N = 13,421) using data from the third National Health and Nutrition Examination Survey (NHANES III) to identify subgroups with similar levels within and across behaviors. Cox-proportional hazards models were used to compare mortality rates between subgroups from cancer, cardiovascular disease (CVD) and all-causes at an average of 16.4 (±6.1) years follow-up. Five behavioral typologies were identified in non-smokers ("Moderates", "Low Risk Factors", "Restaurant Diners", "Moderate Passive Smokers" and "Heavy Passive Smokers"), and four in smokers ("Moderates", "Low Risk Factors", "Heavy Smokers" and "Physically Active"). As a group, "Moderates" had levels of each behavior that were not significantly different from at least one other group. Compared to "Moderates", in non-smokers "Restaurant Diners" had lower hazard from all-cause (hazard ratio (HR):0.84, 95% CI:0.74-0.97) and CVD (HR:0.59, 0.43-0.82) mortality, while "Low Risk Factors" had higher cancer mortality (HR:1.38,1.03-1.84). In smokers, compared to "Moderates", higher hazards for mortality were found for "Heavy Smokers" (all cause: HR:1.34, 1.12-1.60; CVD: HR:1.52, 1.04-2.23; cancer: HR:1.41 1.02-1.96) and "Low Risk Factors" (all-cause: HR:1.58, 1.14-2.17). Taken together, when restaurant dining, PA and smoking exposures are grouped together, novel predictions for mortality occur, suggesting data on multiple behaviors may be informative for risk stratification.

Effect of pesticide exposure on the cholinesterase activity of the occupationally exposed tea garden workers of northern part of West Bengal, India.

Context: Pesticide poisoning and related deaths are a global concern, but there is little information about its effect on the occupationally exposed tea garden workers of North Bengal. Objective: This study investigates the level of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the blood of the tea garden workers at risk of exposure to a mixture of pesticides. Materials and methods: The study sample consisted of pesticide exposed workers, non-exposed (control), smokers and alcoholics. AChE and BuChE activity was measured and tested for significance. Results: Results showed that AChE activity was half in the pesticide exposed individuals than controls (p≤ 0.001). BuChE activity was also significantly decreased in the pesticide exposed individuals than controls (p≤ 0.001), while AChE and BuChE activity in smokers and alcoholics were not different from that of controls. However, significantly decreased AChE and BuChE activities were recorded in pesticide exposed workers compared to smokers and alcoholics. Conclusions: The results indicated that the decrease in enzyme activities in tea garden workers was due to mixed pesticides (containing organophosphates) exposure. Age was not found to influence the enzyme activities. However, the gender had little effect on the enzyme activities but the effect was not so prominent.

The top-down regulation from the prefrontal cortex to insula via hypnotic aversion suggestions reduces smoking craving.

Hypnosis has been shown to have treatment effects on nicotine addiction. However, the neural basis of these effects is poorly understood. This preliminary study investigated the neural mechanisms of hypnosis-based treatment on cigarette smoking, specifically, whether the hypnosis involves a top-down or bottom-up mechanism. Two groups of 45 smokers underwent a smoking aversion suggestion and viewed smoking-related pictures and neutral pictures. One group underwent functional magnetic resonance imaging scanning twice (control and hypnotic states), whereas the other group underwent two electroencephalograph sessions. Our study found that self-reported smoking craving decreased in both groups following hypnosis. Smoking cue-elicited activations in the right dorsal lateral prefrontal cortex (rDLPFC) and left insula (lI) and the functional connectivity between the rDLPFC and lI were increased in the hypnotic state compared with the control state. The delta band source waveforms indicated the activation from 390 to 862 ms at the rDLPFC and from 490 to 900 ms at the lI was significantly different between the smoking and neutral conditions in the hypnotic state, suggesting the activation in the rDLPFC preceded that in the lI. These results suggest that the decreased smoking craving via hypnotic aversion suggestions may arise from the top-down regulation of the rDLPFC to the lI. Our findings provide novel neurobiological evidence for understanding the therapeutic effects of hypnosis on nicotine addiction, and the prefrontal-insula circuit may serve as an imaging biomarker to monitor the treatment efficacy noninvasively.

Cigarette smoking causes a worse long-term outcome in persistent atrial fibrillation following catheter ablation.

INTRODUCTION: Cigarette smoking contributes to the development of atrial fibrosis via nicotine. The impact of smoking on ablation results in persistent atrial fibrillation (AF) is unknown. We aimed to investigate the triggers and long-term outcome between smokers and nonsmokers in the patients with persistent AF after catheter ablation. METHODS: This study included 201 (177 males, 53 ± 10 years old) patients who received index catheter ablation, including pulmonary vein isolation (PVI) and complex fractionated atrial electrograms (CFAEs) ablation for persistent AF, retrospectively. Electrophysiological characteristics at the index procedure and long-term outcome were investigated to determine the differences between smokers and nonsmokers. RESULTS: Baseline characteristics were similar between two groups. Pulmonary vein (PV) triggers were found in all patients in the two groups. There was a higher incidence of nonpulmonary vein (NPV) triggers in smokers than in nonsmokers (61% vs. 31%, P < 0.05). There were no differences of the long-term ablation outcomes between smokers and nonsmokers in Kaplan-Meier analysis. Smokers with PV plus right atrial NPV (RA-NPV) triggers had a higher incidence of recurrence (log-rank P < 0.05) than those without RA-NPV triggers, but not in nonsmokers, after a mean follow-up of 31 ± 25 months. CONCLUSIONS: Smoking increases the incidence of NPV triggers in patients with persistent AF. Smokers who have RA-NPV triggers during index procedure do have a worse outcome after catheter ablation, indicating the harmful effects of nicotine to right atrium.

The thalamo-cortical resting state functional connectivity and abstinence-induced craving in young smokers.

Craving is a significant predicator of smoking relapse. Thus, revealing the neural correlates of craving to smoke in young smokers is important to improve the success of quit attempts. The abstinence-induced craving to smoke has not been explored extensively, although previous studies had investigated the neural substrates of cue-induced craving. Especially, the critical roles of thalamus had been revealed in cigarettes smoking. However, the implication of thalamus resting state functional connectivity (RSFC) in abstinence-induced craving remains unclear. In the current study, by employing a within-subject design in 25 young smokers, both the left and right thalamus RSFC patterns differences were investigated between smoking abstinence condition and smoking satiety condition in young smokers. Moreover, a correlation analysis was employed to assess the relationship between these RSFC changes and abstinence-induced changes in subjective craving. We found young smokers in abstinence state showed reduced RSFC between the left thalamus and right dorsal lateral prefrontal cortex (dlPFC) as well as the right anterior cingulate cortex (ACC) compared with smoking satiety state. There were no significant different RSFC of right thalamus detected across the two sessions. Additionally, the left thalamus-right dlPFC RSFC changes were correlated with the changes in craving induced by 12-h abstinence (i.e., abstinence minus satiety). The present findings provides new evidence that abstinence-induced cravings to smoke are associated with abnormal thalamus RSFC and may shed new insights into the neural mechanism of abstinence-induced craving in young smokers.

Tailoring a NICU-Based Tobacco Treatment Program for Mothers Who Are Dependent on Opioids.

OBJECTIVE: To collect formative information to design a tailored tobacco treatment intervention for women with newborns treated or evaluated for neonatal abstinence syndrome and to explore current tobacco use behaviors and facilitators and barriers to smoking cessation. DESIGN: Qualitative descriptive study. SETTING: An academic medical center in the southern United States. PARTICIPANTS: Mothers (N = 11) of newborns who were treated or evaluated for neonatal abstinence syndrome at birth within the preceding 3 months. Women recruited were older than 18 years and reported opioid dependence and smoking during pregnancy. METHODS: Participants took part in semistructured individual interviews that lasted approximately 1 hour. Interviews were professionally transcribed and analyzed in MAXQDA using content analysis. RESULTS: Five themes emerged from the data: Strategizing to Reduce Risk, Desire to Quit Smoking in the Future, Holding on to Smoking While Working Through Recovery, Feeling Judged by Nurses, and Feeling Supported and Empowered by Nurses. Participants reported that they to reduce risk to their newborns by avoiding second- and thirdhand smoke exposure. Participants wanted to stop smoking but reported many barriers, including multiple life stressors compounded by their newborns' extended stays in the hospital. However, most participants described overall positive experiences and the support of health care providers. CONCLUSION: Holistic tobacco treatment programs that incorporate stress relief and social support and are led by trusted health care providers have the potential to be effective to reduce smoking in new mothers with histories of opioid dependence disorders and smoking and whose newborns are in the NICU.

Forecasting Chronic Diseases Using Data Fusion.

Data fusion, that is, extracting information through the fusion of complementary data sets, is a topic of great interest in metabolomics because analytical platforms such as liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy commonly used for chemical profiling of biofluids provide complementary information. In this study, with a goal of forecasting acute coronary syndrome (ACS), breast cancer, and colon cancer, we jointly analyzed LC-MS, NMR measurements of plasma samples, and the metadata corresponding to the lifestyle of participants. We used supervised data fusion based on multiple kernel learning and exploited the linearity of the models to identify significant metabolites/features for the separation of healthy referents and the cases developing a disease. We demonstrated that (i) fusing LC-MS, NMR, and metadata provided better separation of ACS cases and referents compared with individual data sets, (ii) NMR data performed the best in terms of forecasting breast cancer, while fusion degraded the performance, and (iii) neither the individual data sets nor their fusion performed well for colon cancer. Furthermore, we showed the strengths and limitations of the fusion models by discussing their performance in terms of capturing known biomarkers for smoking and coffee. While fusion may improve performance in terms of separating certain conditions by jointly analyzing metabolomics and metadata sets, it is not necessarily always the best approach as in the case of breast cancer.

Association Between Baseline Corticothalamic-Mediated Inhibitory Control and Smoking Relapse Vulnerability.

Importance: Tobacco use disorder is associated with dysregulated neurocognitive function in the right inferior frontal gyrus (IFG)-one node in a corticothalamic inhibitory control (IC) network. Objective: To examine associations between IC neural circuitry structure and function and lapse/relapse vulnerability in 2 independent studies of adult smokers. Design, Setting, and Participants: In study 1, treatment-seeking smokers (n = 81) completed an IC task during functional magnetic resonance imaging (fMRI) before making a quit attempt and then were followed up for 10 weeks after their quit date. In study 2, a separate group of smokers (n = 26) performed the same IC task during fMRI, followed by completing a laboratory-based smoking relapse analog task. Study 1 was performed at Duke University Medical Center between 2008 and 2012; study 2 was conducted at the Medical University of South Carolina between 2013 and 2016. Main Outcomes and Measures: Associations between corticothalamic-mediated IC, gray-matter volume, and smoking lapse/relapse. Results: Of the 81 study participants in study 1 (cessation study), 45 were women (56%), with mean (SD) age, 38.4 (10.2) years. In study 1, smoking relapse was associated with less gray-matter volume (F1,74 = 28.32; familywise error P threshold = 0.03), greater IC task-related blood oxygenation level-dependent (BOLD) response in the right IFG (F1,78 = 14.87) and thalamus (F1,78 = 14.97) (P < .05), and weaker corticothalamic task-based functional connectivity (tbFC) (F1,77 = 5.87; P = .02). Of the 26 participants in study 2 (laboratory study), 15 were women (58%), with mean (SD) age, 34.9 (10.3). Similar to study 1, in study 2, greater IC-BOLD response in the right IFG (t23 = -2.49; ß = -0.47; P = .02), and weaker corticothalamic tbFC (t22 = 5.62; ß = 0.79; P < .001) were associated with smoking sooner during the smoking relapse-analog task. In both studies, corticothalamic tbFC mediated the association between IC performance and smoking outcomes. Conclusions and Relevance: In these 2 studies, baseline differences in corticothalamic circuitry function were associated with mediated IC and smoking relapse vulnerability. These findings warrant further examination of interventions for augmenting corticothalamic neurotransmission and enhancing IC during the course of tobacco use disorder treatment.

Breathing SPACE-a practical approach to the breathless patient.

Breathlessness is a common symptom that may have multiple causes in any one individual and causes that may change over time. Breathlessness campaigns encourage people to see their General Practitioner if they are unduly breathless. Members of the London Respiratory Network collaborated to develop a tool that would encourage a holistic approach to breathlessness, which was applicable both at the time of diagnosis and during ongoing management. This has led to the development of the aide memoire "Breathing SPACE", which encompasses five key themes-smoking, pulmonary disease, anxiety/psychosocial factors, cardiac disease, and exercise/fitness. A particular concern was to ensure that high-value interventions (smoking cessation and exercise interventions) are prioritised across the life-course and throughout the course of disease management. The approach is relevant both to well people and in those with an underling diagnosis or diagnoses. The inclusion of anxiety draws attention to the importance of mental health issues. Parity of esteem requires the physical health problems of people with mental illness to be addressed. The SPACE mnemonic also addresses the problem of underdiagnosis of heart disease in people with lung disease and vice versa, as well as the systematic undertreatment of these conditions where they do co-occur.

[Real Time Fuctional Magnetic Resonance Imaging Biofeedback: a New Generation of Neurotherapy].

The review summarizes the data related to the potential of the real time fMRI biofeedback (the rt-fMRI), a novel technology implementing instructing patients to modify the neural activity in the certain brain regions related to the disordered function. The recent positive results were gained for a treatment of the post-stroke impairments, the Parkinson disease, the pain syndrome, the tinnitus, the alcohol and nicotine abuse, the major depression, and phobias of contamination and spiders. The intervention Was found to be less promising for schizophrenia and nearly ineffective for the criminal antisocial personality disorder. The reliability of the results is mostly poor due to suboptimal study designs, lack of the control groups, and insufficient sample sizes. The article deals with biological basis of the technology, its current applications and perspectives; and also its method- ologicdl and methodical problems.

Quit Intentions Moderate Subjective and Physiological Responses to Acute Nicotine Replacement Therapy Administration in Dependent Smokers.

INTRODUCTION: This study assessed the impact of expectancy and administration components of acute nicotine inhaler use on craving, heart rate, and smoking behavior in smokers with varying intentions to quit. METHODS: 47 dependent smokers that differed in self-reported intention to quit (no intention to quit during the next month N = 26 vs. intention to initiate a quit attempt within 2 weeks N = 21) were randomly administered a 4 mg nicotine or nicotine-free inhaler across two sessions. Instructions regarding the inhaler's nicotine content (expect nicotine vs. expect nicotine-free; nicotine expectancy) and flavor (mint vs. citrus) varied across sessions. Craving and heart rate were assessed before and after inhaler administration (two-second inhalations every 10 seconds over 20 minutes). Next, participants were offered an opportunity to self-administer puffs of their preferred tobacco brand during an hour-long progressive ratio task. RESULTS: Across participants, nicotine expectancy independently reduced withdrawal related craving (p = .018), but no comparable effects of nicotine administration were evident. In quitting motivated smokers, nicotine expectancy and administration interacted to reduce intention to smoke (p = .040), while nicotine expectancy (p = .047) and administration (p = .025) independently reduced intention to smoke in quitting unmotivated smokers. Blunted heart rate reactivity to nicotine administration was observed in quitting motivated relative to unmotivated smokers (p = .042); however, neither expectancy nor administration impacted smoking behavior in either group (p values > .25). CONCLUSIONS: Findings indicate that participant quitting intentions moderate acute nicotine replacement therapy responses. In quitting motivated smokers, a combination of pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving. IMPLICATIONS: Findings from this study demonstrate that motivations to quit smoking moderate subjective and physiological responses to acute nicotine administration and expectancy in dependent cigarette smokers. Quitting motivated smokers showed blunted heart rate reactivity to nicotine administration, suggesting that they may be less sensitive to the rewarding aspects of nicotine consumption. Nicotine administration and expectancy were found to interact to reduce craving in quitting motivated but not in unmotivated smokers, suggesting that pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving in smokers who plan to quit.

Are addiction-related memories malleable by working memory competition? Transient effects on memory vividness and nicotine craving in a randomized lab experiment.

BACKGROUND AND OBJECTIVES: Experimental research suggests that working memory (WM) taxation reduces craving momentarily. Using a modified Eye Movement Desensitization and Reprocessing (EMDR) procedure, prolonged reductions in craving and relapse rates in alcohol dependence have been demonstrated. Modified EMDR-procedures may also hold promise in smoking cessation attempts. A proof-of-concept study was conducted to narrow the gap between WM-taxation experiments and clinical EMDR studies. To this end the clinical EMDR-procedure was modified for use in a laboratory experiment. METHODS: Daily smokers (n = 47), abstaining overnight, were allocated (by minimization randomization) to one of two groups using a parallel design. In both cases a modified EMDR-procedure was used. In the experimental group (n = 24) eye movements (EM) were induced while control group participants (n = 23) fixed their gaze (not taxing WM). During 6 min trials, craving-inducing memories were recalled. Craving, vividness of target memories, and smoking behavior were assessed at several variable-specific time-points between baseline (one week pre-intervention) and one week follow-up. RESULTS: The experimental group showed significant immediate reductions of craving and vividness of targeted memories. However, these effects were lost during a one-week follow-up period. CONCLUSIONS: A limited dose of WM-taxation, in the form of EM in a modified EMDR-procedure, resulted in transient effects on memory vividness and nicotine craving. EM provide a valuable way of coping with the acute effects of craving during smoking cessation attempts. Other aspects of the EMDR-procedure may provide additional effects. Component and dose-response studies are needed to establish the potential of EMDR-therapy in smoking cessation.

Tobacco use is associated with reduced amplitude and intensity dependence of the cortical auditory evoked N1-P2 component.

RATIONALE: Tobacco use is linked to cerebral atrophy and reduced cognitive performance in later life. However, smoking-related long-term effects on brain function remain largely uncertain. Previous studies suggest that nicotine affects serotonergic signaling, and the intensity dependence (alias loudness dependence) of the auditory evoked N1-P2 potential has been proposed as a marker of serotonergic neurotransmission. OBJECTIVE: In the present study, we assesed the effects of chronic smoking on amplitude and intensity dependence of the auditory evoked N1-P2 potential. METHODS: Subjects underwent a 15-min intensity dependence of auditory evoked potentials (IAEP) paradigm. From N = 1739 eligible subjects (40-79 years), we systematically matched current smokers, ex-smokers, and never-smokers by sex, age, alcohol and caffeine consumption, and socioeconomic status. Between-group differences and potential dose-dependencies were evaluated. RESULTS: Analyses revealed higher N1-P2 amplitudes and intensity dependencies in never-smokers relative to ex- and current smokers, with ex-smokers exhibiting intermediate intensity dependencies. Moreover, we observed pack years and number of cigarettes consumed per day to be inversely correlated with amplitudes in current smokers. CONCLUSIONS: According to the IAEP serotonin hypothesis, our results suggest serotonin activity to be highest in current smokers, intermediate in ex-smokers, and lowest in never-smokers. To our knowledge, the present study is the first providing evidence for a dose-dependent reduction in N1-P2 amplitudes. Further, we extend prior research by showing reduced amplitudes and intensity dependencies in ex-smokers even 25 years, on average, after cessation. While we can rule out several smoking-related confounders to bias observed associations, causal inferences remain to be established by future longitudinal studies.