Nicotine-dependent Subjects Research Articles

Biochemical and genetic biomarkers associated with nicotine dependence in Mexican smokers.

Cigarette smoking remains an important health concern and is still a leading cause of preventable mortality. Nicotine is the substance responsible for sustained tobacco use and dependence. Identification of biomarkers underlying nicotine dependence behavior is important to identify people at risk for this dependence. In the present study, we identified biochemical and genetic biomarkers of nicotine dependence detected by the Fagerström Test for Nicotine Dependence (FTDN) in Mexican smokers. The nicotine metabolites nicotine-N'-oxide, trans-3'-hydroxycotinine-glucuronide (3HC-O-Gluc), and nicotine-N-Gluc (Gluc) were useful to differentiate nicotine-dependent from non-dependent subjects (p < .0001) with an area under the curve (AUC) of 0.7818. Genetic variants in CYP2A6, FMO3, and UGT2B7 (rs2431413, rs28363545, and rs7439326, respectively) were associated with nicotine dependence (p = .03, p = .01, p = .01, respectively). Variations in the enzymatic activity of CYP2A6 were associated with altered nicotine-N'-oxide and 3HC-O-Gluc levels. Decreased urinary levels of 3HC-O-Gluc and increased nicotine-N'-oxide were associated with a decrease in the functional activity of CYP2A6. A strong positive correlation was observed between the ratio of urinary 3HC/cotinine, a measure of CYP2A6 activity, and the levels of 3HC-O-Gluc (p < .0001, r = .6835), while a strong negative correlation was observed with nicotine-N'-oxide (p < .0001, r = .6522) in nicotine-dependent subjects. No correlations were observed in non-nicotine-dependent subjects. These data suggest that particular urinary nicotine metabolites and genetic variants involved in nicotine metabolism are useful to identify subjects with nicotine dependence in the Mexican population.

Relación entre impulsividad, inflexibilidad psicológica y síntomas de psicopatología en pacientes con dependencia de nicotina

Introduction: high levels of impulsivity and psychological inflexibility characterize nicotine dependent subjects and some psychopathology symptoms are also related to the tobacco consumption but it is unknown if there is a relationship between these. Objective: to evaluate the correlation of impulsivity with psychological inflexibility, and symptoms of psychopathology in nicotine dependent subjects. Method: an observational study was carried out, the universe of which was 24 patients who attended the smoking clinic of the State Center for Mental Health of Puebla for the first time (January-March 2020). The instruments were applied: the Fagerström test to measure nicotine dependence, the Barratt impulsivity scale, the Acceptance and Action questionnaire to measure the inflexibility score and the symptom list, to identify psychopathology symptoms. Correlations were made with the Spearman test. Results: in nicotine dependence subjects (moderate and severe) no correlation was found between impulsivity and psychological inflexibility. There was a moderate correlation of impulsivity with anxiety (rs = .467, p () .05), somatization (rs = .451, p () .05) and hostility (rs = .426, p () .05). None of the psychopathology symptoms correlated with psychological inflexibility. The comparison between high and low impulsivity and psychological inflexibility showed that the high impulsivity and low inflexibility groups had high scores for psychopathology symptoms. Only the anxiety scale marked significant differences according to the level of impulsivity. Discussion and conclusions: in the subjects of the sample the correlations between impulsivity and symptoms of anxiety somatization and hostility suggest identifying these characteristics early to improve abstinence rates in them.

DNA Methylation of the Dopamine Transporter DAT1 Gene-Bliss Seekers in the Light of Epigenetics.

DNA methylation (leading to gene silencing) is one of the best-studied epigenetic mechanisms. It is also essential in regulating the dynamics of dopamine release in the synaptic cleft. This regulation relates to the expression of the dopamine transporter gene (DAT1). We examined 137 people addicted to nicotine, 274 addicted subjects, 105 sports subjects and 290 people from the control group. After applying the Bonferroni correction, our results show that as many as 24 out of 33 examined CpG islands had statistically significantly higher methylation in the nicotine-dependent subjects and athletes groups compared to the control group. Analysis of total DAT1 methylation revealed a statistically significant increase in the number of total methylated CpG islands in addicted subjects (40.94%), nicotine-dependent subjects (62.84%) and sports subjects (65.71%) compared to controls (42.36%). The analysis of the methylation status of individual CpG sites revealed a new direction of research on the biological aspects of regulating dopamine release in people addicted to nicotine, people practicing sports and people addicted to psychoactive substances.

Association of Polymorphism CHRNA5 and CHRNA3 Gene in People Addicted to Nicotine.

Smoking is a chronic and relapsing addictive trait that harms public health. Among the many identified genetic variants of nicotine dependence, the variants in the CHRNA5/A3/B4 gene cluster on chromosome 15 that encode the α5, α3, and β4 subunits have recently received a lot of attention. Importantly, variants in this gene cluster have been associated with nicotine addiction. Among the many significant variants in this cluster, the polymorphism SNP rs16969968 seems to be the most interesting factor in nicotine addiction. This polymorphism causes an amino acid change from aspartate to asparagine at position 398 of the α5 nicotinic receptor protein sequence. Our study aimed to analyze three polymorphic variants: the rs16969968 located in the CHRNA5 gene, the rs578776 and rs1051730 located in the CHRNA3 gene in nicotine-addicted subjects, and in controls. Our study encompasses an association analysis of genotypes and haplotypes. A group of 401 volunteers was recruited for the study and divided into two groups: the study group consisted of addicted smokers and a control group of 200 unrelated non-smokers who were not dependent on any substance and healthy. A statistically significant difference was observed in the frequency of genotypes of the rs1051730 polymorphism of the CHRNA3 gene (χ2 = 6.704 p = 0.035). The T/T genotype was statistically significantly more frequent in the group of nicotine-dependent subjects. The haplotypes rs16969968, rs578776, and rs1051730 were distinguished, of which the G-T-T and G-C-T haplotypes were present only in the study group. With differences in frequencies, statistical significance was noted—for the G-T-T haplotype p = 0.01284 and the G-C-T haplotype p = 0.00775. The research stated that novel haplotypes G-T-T and G-C-T, though with very low-frequency variants in CHRNA3, were associated with nicotine addiction.

Methylation in the Promoter Region of the Dopamine Transporter DAT1 Gene in People Addicted to Nicotine

The dopaminergic system is a crucial element of the addiction processes. The dopamine transporter modulates the dynamics and levels of released dopamine in the synaptic cleft. Therefore, regulation of dopamine transporter (DAT1) gene expression is critical for maintaining homeostasis in the dopaminergic system. The aim of our study is evaluation of the methylation status of 33 CpG islands located in the DAT1 gene promoter region related to nicotine dependency. We investigated 142 nicotine-dependent subjects and 238 controls. Our results show that as many as 14 of the 33 CpG islands tested had statistically significantly higher methylation in the nicotine-dependent group compared to the control group. After applying Bonferroni correction, the total number of methylation sites was also significantly higher in the dependent subjects group. The analysis of the methylation status of particular CpG sites revealed a new direction of research regarding the biological aspects of nicotine addiction.

SmoCuDa: A Validated Smoking Cue Database to Reliably Induce Craving in Tobacco Use Disorder

Background: Cue-reactivity paradigms provide valuable insights into the underlying mechanisms of nicotine craving in nicotine-dependent subjects. In order to study cue-driven nicotine craving, robust and validated stimulus datasets are essential. Objectives: The aim of this study was to generate and validate a large set of individually rated smoking-related cues that allow for assessment of different stimulus intensities along the dimensions craving, valence, and arousal. Methods: The image database consisted of 330 visual cues. Two hundred fifty smoking-associated pictures (Creative Commons license) were chosen from online databases and showed a widespread variety of smoking-associated content. Eighty pictures from previously published databases were included for cross-validation. Forty volunteers with tobacco use disorder rated “urge-to-smoke,” “valence,” and “arousal” for all images on a 100-point visual analogue scale. Pictures were also labelled according to 18 categories such as lit/unlit cigarettes in mouth, cigarette end, and cigarette in ashtray. Results: Ratings (mean ± SD) were as follows: urge to smoke, 44.9 ± 13.2; valence, 51.2 ± 7.6; and arousal, 54.6 ± 7.1. All ratings, particularly “urge to smoke,” were widely distributed along the whole scale spectrum. Conclusions: We present a novel image library of well-described smoking-related cues, which were rated on a continuous scale along the dimensions craving, valence, and arousal that accounts for inter-individual differences. The rating software, image database, and their ratings are publicly available at https://smocuda.github.io.

Emotion recognition and its relation to prefrontal function and network in heroin plus nicotine dependence: a pilot study.

Many patients with substance use disorders (SUDs) live in a stressful environment, and comorbidity is not uncommon. Understanding the neural mechanisms underlying heroin and nicotine dependences and their relationships to social cognition could facilitate behavioral therapy efficacy. We aimed to provide a translational approach that leads to identifying potential biomarkers for opioid use disorder (OUD) susceptibility during recovery. We examined the clinical characters and the relationships between theory of mind (ToM) and executive functions in three groups: heroin plus nicotine-dependent (HND) patients who had remained heroin abstinent ( months), nicotine-dependent (ND) subjects, and healthy controls (C). The domains included emotion recognition, inhibition, shifting, updating, access, and processing speed. Resting-state functional connectivity (rsFC), ToM task-induced functional connectivity, and brain networks were then explored among 21 matched subjects using functional near-infrared spectroscopy. HND enhanced the severities of anxiety, depression, and hyperactivity. Inhibition domain was impaired in both HND and ND. No impairment in domains of emotion recognition, access, and update was observed. HND demonstrated enhanced rsFC in the medial prefrontal cortex and orbitofrontal cortex (OFC) and decreased ToM-induced connectivity across the PFC. The right superior frontal gyrus in the OFC (oSFG; , , and ) was associated with working memory and emotion recognition in HND. Using a neuroimaging tool, these results supported the prominent reward-deficit-and-stress-surfeit hypothesis in SUDs, especially OUD, after protracted withdrawal. This may provide an insight in identifying potential biomarkers related to a dynamic environment.

Affective temperaments in nicotine-dependent and non-nicotine-dependent individuals

&lt;b&gt;Background&lt;/B&gt;&lt;br /&gt; One of the smoking risk factors influencing nicotine dependency may be human personality; however, few studies have examined the association between Akiskal’s affective temperaments and smoking in adults. Our study aims to evaluate the associations between nicotine dependence and affective temperaments using the TEMPS-A.&lt;br /&gt; &lt;br /&gt; &lt;b&gt;Participants and procedure&lt;/B&gt;&lt;br /&gt; The sample in this study consisted of 678 healthy Caucasian adults aged from 17 to 69 years, including 134 self-declared nicotine-dependent subjects (89 females and 45 males) and 544 self-declared non-nicotine-dependent subjects (352 females and 192 males). The Polish version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) was used to assess affective temperaments (depressive, cyclothymic, hyperthymic, irritable and anxious).&lt;br /&gt; &lt;br /&gt; &lt;b&gt;Results&lt;/B&gt;&lt;br /&gt; Nicotine-dependent individuals scored higher on cyclothymic, irritable and anxious temperaments than non-nicotine-dependents (no significant differences with regard to depressive and hyperthymic temperaments). Among the nicotine-dependent individuals, females scored higher on anxious temperaments than males (no differences with regard to the other affective temperaments), and among the non-nicotine-dependent individuals, females exhibited more depressive, cyclothymic and anxious temperaments than males, while males exhibited more hyperthymic temperaments than females.&lt;br /&gt; &lt;br /&gt; &lt;b&gt;Conclusions&lt;/B&gt;&lt;br /&gt; The results suggest that affective, cyclothymic and irritable temperaments in both genders and anxious temperaments in females may be predictors of nicotine dependence in adults.

Study of pharmacotherapy role in smoking cessation giving an insight into the frequency of smoking among Zagazig University Hospitals’ staff in 2013

Background“Smoking is the main avoidable cause of death around the world”. It’s prevalence is about one billion smokers in the global adult population. “The most cost effective and well-documented methods for smoking cessation are professional advice combined with the nicotine replacement therapy”. So the main aim of hospital staff must be to give advices about smoking cessation and the ways to it. The aim of this work was to study the pharmacotherapy role in smoking cessation giving an insight into the frequency of smoking among Zagazig University Hospitals’ staff in 2013. Subjects and methodsThis epidemiological, observational and prospective study was carried out at Zagazig University Hospitals from the period January 2013 to December 2013. Subjects150 of those current smokers agreed to answer the study questionnaire and share in this study. The included subjects were 144 males and 6 females with a mean age of 39.48±11.95years. MethodsThe studied subjects were subjected to the following: (1) personal history including: smoking history and family history, (2) routine investigations and (3) plain X-ray. The studied subjects (150) were divided into 2 groups according to their agreement for taking pharmacotherapy: group I: included 111 subjects treated by behavioral therapy alone for 3months. Group II: included 39 subjects treated by behavioral therapy plus pharmacotherapy (Bupropion SR tablet) for 3months. ResultsA statistically highly significant percentage of subjects who did previous trial of quitting was found in group II than that in group I. Also, there was a statistically highly significant percentage of subjects who are less nicotine dependent in group II than that in group I, but the reverse was present in highly nicotine dependent subjects according to Fagerstrom score. The final outcome of quitting trial with a successful cessation rate was 48%, while the failed cessation rate was 52% and there was a statistically significant higher successful rate in group II (69.3%) than that in group I (40.5%). As regards occupation, the physicians had statistically highly significant higher levels of successful rate than para-medicals who had high levels of failed cessation rate. A statistically highly significant increase in the percentage of other smoker family member was found in failed cessation group than that in successful cessation one. Regarding Fagerstrom score, there were statistically significant increases in percentage of subjects who were less nicotine dependent in successful cessation group than that in failed cessation one and also in percentage of subjects who were highly nicotine dependent in failed cessation group than that in successful one. Conclusion(1) Programs promoting smoking cessation including behavioral therapy in addition to the complementary role of pharmacotherapy (Bubropion SR) enhanced the chance of success in smoking cessation. (2) This pilot study (regarding the number of the studied individuals) pointed to the smoking dilemma in a locality where smoking behavior should be brought to a minimum especially among physicians.

Agonist and antagonist effects of cytisine in vivo

Varenicline, the most successful smoking cessation aid, is a selective partial agonists at α4β2* nicotinic receptors. Its efficacy is likely to be shared by other drugs with similar receptor action, including cytisine. The present study aimed to characterize behavioral effects of cytisine compared with nicotine using locomotor activity tests, intracranial self-stimulation of ventral tegmental area (discrete-trial threshold current intensity titration procedure), drug discrimination (0.6 mg/kg nicotine from vehicle), physical dependence (osmotic minipumps delivering 6 mg/kg/day of nicotine) and intravenous nicotine self-administration (0.01 mg/kg per infusion) in adult Wistar rats. Cytisine (1–3 mg/kg) partially substituted for nicotine and at the highest dose tended to antagonize nicotine's discriminative stimulus effects. Nicotine (0.05–0.4 mg/kg), but not cytisine (0.3–3 mg/kg), lowered ICSS thresholds and cytisine dose-dependently reversed effects of nicotine. Nicotine (0.15–0.6 mg/kg), but not cytisine (0.3–3 mg/kg), stimulated locomotor activity and cytisine (3 mg/kg) fully reversed these effects of nicotine. Acute pretreatment with nicotine (0.15–0.6 mg/kg), but not cytisine (0.3–3 mg/kg), reinstated extinguished nicotine self-administration. Continuous infusion of nicotine induced physical dependence, as indicated by reduced rates of food-reinforced responding induced by a challenge dose of mecamylamine. At the highest tested dose (3 mg/kg), cytisine tended to reduce response rates irrespective of whether the rats were continuously exposed to nicotine or saline. Cytisine behaves like a weak partial agonist, mimicking effects of nicotine to a limited degree. Although cytisine reversed several effects of nicotine, it seemed to have a reduced potential to produce withdrawal signs in nicotine-dependent subjects.

Do nicotine dependent subjects show functional differences in response to risk?

Event Abstract Back to Event Do nicotine dependent subjects show functional differences in response to risk? Louise Curley1*, Rob R. Kydd2, Ian J. Kirk3, Bruce R. Russell1 and Robert Hester4 1 University of Auckland, School of Pharmacy, New Zealand 2 University of Auckland, Department of Psychological Medicine, New Zealand 3 University of Auckland, Department of Psychology, New Zealand 4 University of Melbourne, School of Psychological Sciences, Australia The National Institute on Drug Abuse in the US describes drug addiction as a chronic and complex brain disease. Research has shown prolonged drug use causes changes in the brain's reward system that prompts compulsive drug use. However, to date studies investigating regional activation associated with risk-based decision making in drug users have typically not dissociated probability from magnitude of reward i.e. the increase in reward has been associated with an increase in the risk associated decision. We developed two tasks to investigate aspects of reward based decision making and to evaluate if the outcome of the gamble (i.e. win or loss) affected future selection. Nicotine dependent and healthy control subjects (18-40 years) behavioural responses were recorded whilst completing the two tasks. Behavioural data was analysed using SPSS. The two groups were compared for Reaction Time (RT) and accuracy. The influence of previous outcomes on future decision making was assessed by the proportion of large/small magnitude bets that followed losses/ gains. Data analysis showed there were no significant differences in either RT or accuracy, however the effects of positive or negative outcomes showed differences in future decision making between the two groups. The study shows clear differences during the evaluation of risk between nicotine dependent and healthy control subjects. The differences in reward selection after feedback reflects possible changes in reward based decision making in those with nicotine dependence. Keywords: Humans, Reward, risky decision making, functional MRI, Nicotine dependence Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Cognition and Executive Processes Citation: Curley L, Kydd RR, Kirk IJ, Russell BR and Hester R (2015). Do nicotine dependent subjects show functional differences in response to risk?. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00161 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Dr. Louise Curley, University of Auckland, School of Pharmacy, Auckland, New Zealand, l.curley@auckland.ac.nz Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Louise Curley Rob R Kydd Ian J Kirk Bruce R Russell Robert Hester Google Louise Curley Rob R Kydd Ian J Kirk Bruce R Russell Robert Hester Google Scholar Louise Curley Rob R Kydd Ian J Kirk Bruce R Russell Robert Hester PubMed Louise Curley Rob R Kydd Ian J Kirk Bruce R Russell Robert Hester Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Effect of activated peripheral κ-opioid receptors on the action of nicotine and its withdrawal in nicotine-dependent rats.

We studied the possibilities of modulating the effects of nicotine and its withdrawal in nicotine-dependent rats by peripheral injection of κ-opioid receptor agonist ICI 204,448. Injection of nicotine to rats previously treated with nicotine for 14 days reduced motor activity, suppressed metabolism, and increased food intake. In rats receiving ICI 204,448 after chronic administration of nicotine, food intake did not differ from that in control animals receiving isotonic NaCl solution. ICI 204,448 had virtually no effect on suppression of motor activity and metabolism. The rats receiving the last injection of nicotine 24 h prior to the experiment demonstrated an increase in metabolism, locomotor activity, and food intake. In these animals, ICI 204,448 completely abolished the effects of nicotine withdrawal. It was found that peripheral administration of compound ICI 204,448 did not significantly inhibit the effect of nicotine in nicotine-dependent rats, but abolished symptoms of nicotine withdrawal. It can be hypothesized that nicotine withdrawal syndrome is related to inhibition of dopamine release in the nucleus accumbens probably caused by enhanced κ-opioid activity in presynaptic terminals. Activation of peripheral κ-opioid receptors apparently suppressed (via vagal afferent pathways) central κ-opioid activity and reduced nicotine withdrawal symptoms in nicotine-dependent subjects.

P.2.c.004 Frontopolar inefficiency and anterior cingulate overactivation during working memory: early stage abnormalities in bipolar disorder

When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking.We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (≤1.5 hours abstinence) and abstinence (≥14 hours abstinence) conditions.Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels.We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety.

Association study of 45 candidate genes in nicotine dependence in Han Chinese

Numerous genetic linkages, association studies have been performed in different ethnic groups and revealed many susceptibility loci and genes for nicotine dependence. However, limited similar researches were performed in Han Chinese. This study was designed to investigate the association of candidate genes with nicotine dependence in Han Chinese. We genotyped 384 SNPs within 45 candidate genes with nicotine dependence in a Han Chinese population consisting 223 high nicotine dependent subjects and 257 low nicotine dependent subjects by employing GoldenGate genotyping assay (Illumina). Following association analysis was performed using PLINK software. Individual SNP-based association analysis revealed that nine SNPs located in DRD3 (rs2630351), DRD5 (rs1967550), MAP3K4 (rs2314378), DDC (rs11575461), CHRNB3 (rs4954), GABBR2 (rs2779562), DRD2 (rs11214613 and rs6589377) and CHRNA4 (rs2236196) were significantly associated with FTND after correction for multiple testing with the p values from 2.59×10−7 to 9.99×10−5. Haplotype-based association analysis revealed haplotype G-A-A formed by rs2630351, rs167771 and rs324032 and haplotype G-G-G-A formed by rs3773678, rs2630349, rs2630351 and rs167771 in DRD3; haplotype of G-A formed by rs2779562 and rs2808566 in GABBR2 and haplotype of T-T-A-G-A formed by rs6832644, rs4057797, rs9764, rs4552421 and rs10033119 in NPY1R are associated with FTND (p=3.61×10−7–8.78×10−6). Our results provided confirmation of the previous findings that DRD2, DRD3, DDC, CHRNB3, GABBR2 and CHRNA4 are associated with nicotine dependence. Furthermore, we for the first time report a significant association between nicotine dependence and DRD5, MAP3K4 and NPY1R. These findings need independent replication in the future studies.

Factors underlying prefrontal and insula structural alterations in smokers

Based upon previous reports of alterations in white matter integrity and gray matter density in smokers, we examined these markers in a large, well-matched sample of smokers and non-smokers. We further investigated the effect of heavy cigarette exposure by using pack-years and the effects of two relatively stable, highly heritable traits in smokers (Fagerström Test of Nicotine Dependence (FTND), a measure of severity of nicotine dependence and Toronto Alexithymia Scale (TAS-20), a stable personality trait related to smoking). Forty-eight nicotine-dependent subjects and 48 matched controls were included in the analyses, with smokers also subdivided into high/low dependence and high/low pack-years smokers. White matter integrity (fractional anisotropy (FA)) and gray matter density (voxel-based morphometry (VBM)) were measured and compared across groups. Gray matter density was lower in left prefrontal cortex (PFC) in high pack-years smokers and was inversely related to pack-years. In contrast, left insular cortex gray matter density was higher in smokers and associated with TAS-20 total score and with difficulty-identifying-feelings factor. Further, the most highly dependent smokers showed lower prefrontal FA, which was negatively correlated with FTND. There was no correlation between pack-years and FTND in our smoker population. These data suggest chronic tobacco use is correlated with prefrontal gray matter damage , while differences in insula gray matter and PFC white matter appear to reflect stable and heritable differences between smokers and non-smokers.

An open-label study of naltrexone and bupropion combination therapy for smoking cessation in overweight and obese subjects

A combination of sustained release (SR) naltrexone (32 mg/day) and bupropion SR (360 mg/day) plus behavioral counseling was evaluated for the treatment of smoking cessation and mitigation of nicotine withdrawal and weight gain. Thirty overweight or obese nicotine-dependent subjects were enrolled in a 24-week, open-label study; 85% and 63% completed 12 and 24 weeks, respectively. The target quit date was Week 4. Week 4–12 continuous abstinence rate was 48%, 78% of subjects achieved CO ≤ 10 ppm, serum cotinine decreased from 185 to 48 μg/L, and tobacco use decreased from 129 to 14 cigarettes/week. Similar results were seen at Week 24. Body weight was essentially unchanged (Week 12: − 0.1%; Week 24: + 0.4%). Except for a transient significant increase 1 week after the target quit date ( p < 0.05), nicotine withdrawal scores did not change. The most common adverse events were nausea, insomnia, and constipation. These tended to be transient and mild or moderate in severity. In overweight or obese smokers, naltrexone/bupropion combination therapy with behavioral counseling was associated with decreased nicotine use, limited nicotine withdrawal symptoms, and no significant weight gain.

Relationship of Nicotine Dependence, Subsyndromal and Pathological Gambling, and Other Psychiatric Disorders

Nicotine dependence frequently co-occurs with subsyndromal and pathological levels of gambling. The relationship of nicotine dependence, levels of gambling pathology, and other psychiatric disorders, however, is incompletely understood. To use nationally representative data from the National Epidemiologic Survey on Alcohol and Related Conditions to examine the influence of DSM-IV nicotine dependence on the association between pathological gambling severities and other psychiatric disorders. Face-to-face interviews were conducted with 43,093 adults living in households and group-quarters in the United States. The main outcome measure was the co-occurrence of current nicotine dependence and Axis I and II disorders and severity of gambling based on the 10 inclusionary diagnostic criteria for pathological gambling. The study was conducted from 2001 to 2002. Among non-nicotine-dependent respondents, increasing gambling severity was associated with greater psychopathology for the majority of Axis I and II disorders. This pattern was not uniformly observed among nicotine-dependent subjects. Significant nicotine-by-gambling-group interactions were observed for multiple Axis I and II disorders. All significant interactions involved stronger associations between gambling and psychopathology in the non-nicotine-dependent group. In a large national sample, nicotine dependence influences the associations between gambling and multiple psychiatric disorders. Subsyndromal levels of gambling are associated with significant psychopathology. Nicotine dependence accounts for some of the elevated risks for psychopathology associated with subsyndromal and problem/pathological levels of gambling. Additional research is needed to examine specific prevention and treatment for individuals with problem/pathological gambling with and without nicotine dependence.

Association of Low Striatal Dopamine D 2 Receptor Availability With Nicotine Dependence Similar to That Seen With Other Drugs of Abuse

All drugs of abuse induce a phasic dopamine release within the striatum that does not undergo habituation. Prolonged substance consumption impairs the natural function of the mesolimbic dopamine system, as shown by a decrease in the availability of striatal dopamine 2 (D(2)) receptors in patients suffering from cocaine, heroin, amphetamine, and alcohol dependence. However, it is unclear whether similar changes can also be observed in heavy-smoking nicotine-dependent smokers. In vivo D(2)/D(3) receptor availability was determined with [ (18)F]fallypride positron emission tomography in 17 heavy-smoking nicotine-dependent subjects and in 21 age-matched never-smoking comparison subjects. The smokers were scanned twice: first, during a period of usual consumption and second, 24 hours after smoking cessation. Independent of the withdrawal status, the nicotine-dependent smokers displayed significantly less availability of D(2)/D(3) receptors within the bilateral putamen functionally covering parts of the dorsal striatum, as compared to the never-smoking subjects. Nicotine craving under the consumption condition correlated positively with D(2)/D(3) receptor availability within the ventral striatum but negatively with D(2)/D(3) receptor availability within the anterior cingulate and inferior temporal cortex. Similar to other types of substance abuse, nicotine dependence is associated with low availability of dorsal striatal D(2)/D(3) receptors. In contrast to previous findings on abstinent alcohol-dependent patients, nicotine craving seems to be maintained by a region-specific shift in D(2)/D(3) receptor availabilities, with higher availability within the ventral striatum but lower availability within the anterior cingulate and inferior temporal cortex.

Divided Doses for Methadone Maintenance

Divided Doses for Methadone Maintenance

Association of attentional network function with exon 5 variations of the CHRNA4 gene

Mutational analyses in xenopus oocyte and mice models indicate that the positive effect of nicotine on attention may be modulated by genetic variations within exon 5 of the alpha4 subunit of the nicotinergic acetylcholine receptor gene CHRNA4. The potential relevance of exon 5 is further emphasized by two recent family-based association studies of nicotine dependence because subgroups of nicotine-dependent subjects are thought to 'self-medicate' attentional deficits with nicotine. We investigated a synonymous single nucleotide polymorphisms (SNP): rs1044396, which has recently been associated with nicotine-dependence, plus two adjacent synonymous SNPs rs1044394 and rs1044393 in exon 5 of n = 47 unrelated healthy Caucasian subjects (age: 22.7 +/- 1.7 years; sex: n = 23 males; regular smokers: n = 19). Attentional network function was assessed in supplementary motor area/anterior cingulate (SMA/ACC) and parietal cortex with functional magnetic resonance imaging during an attention-requiring visual oddball task. SNP rs1044396 showed genotype effects on attentional network function both in the SMA/ACC and parietal cortex in the absence of overt behavioral effects. In the parietal cortex, a gene-dosage effect was seen. Comparable genotype effects were also found for the other two SNPs. This investigation provides first evidence that attentional network function may be modulated by genetic variations within CHRNA4 exon 5. If confirmed, future studies need to address what 'functional' polymorphisms are causative for the observed effects.