Abstinent Alcohol Dependence Research Articles

Alterations in white matter microstructure in alcohol and alcohol‐polydrug dependence: Associations with lifetime alcohol and nicotine exposure

Evidence suggests that alcohol dependence (AD) is associated with microstructural deficits in white matter, but the relationship with lifetime alcohol exposure and the impact of polydrug dependence is not well understood. Using diffusion tensor magnetic resonance (MR) imaging, we examined white matter microstructure in relation to alcohol and polydrug dependence using data from the Imperial College Cambridge Manchester (ICCAM) platform study. Tract‐based spatial statistics were used to examine fractional anisotropy (FA) in a cohort of abstinent AD participants, most of whom had a lifetime history of dependence to nicotine. A further subgroup also had a lifetime history of dependence to cocaine and/or opiates. Individuals with AD had lower FA throughout the corpus callosum, and negative associations with alcohol and nicotine exposure were found. A group‐by‐age interaction effect was found showing greater reductions with age in the alcohol‐dependent group within corpus callosum, overlapping with the group difference. We found no evidence of recovery with abstinence. A comparison of alcohol‐only‐ and alcohol‐polydrug‐dependent groups found no differences in FA. Overall, our findings show that AD is associated with lower FA and suggest that these alterations are primarily driven by lifetime alcohol consumption and cigarette smoking, showing no relationship with exposure to other substances such as cocaine, opiates or cannabis. Reductions in FA across the adult lifespan are more pronounced in AD and offer further support for the notion of accelerated ageing in relation to alcohol dependence. These findings highlight there may be lasting structural differences in white matter in alcohol dependence, despite continued abstinence.

Predictors of abstinence, no heavy drinking days, and a 2-level reduction in World Health Organization drinking levels during treatment for alcohol use disorder in the COMBINE study.

Data from trials of medications for alcohol use disorder (AUD) can be used to identify predictors of drinking outcomes regardless of treatment, which can inform the design of future trials with heterogeneous populations. Here, we identified predictors of abstinence, no heavy drinking days, and a 2-level reduction in World Health Organization (WHO) drinking levels during treatment for AUD in the Combined Pharmacotherapies and Behavioral Interventions (COMBINE) Study. We utilized data from the COMBINE Study, a randomized placebo-controlled trial evaluating the efficacy of naltrexone and acamprosate, both alone and in combination, for AUD (n=1168). A tree-based machine learning algorithm was used to construct classification trees predicting abstinence, no heavy drinking days, and a 2-level reduction in WHO drinking levels in the last 4 weeks of treatment, based on 89 baseline variables. The final tree for predicting abstinence had one split based on consecutive days abstinent prior to randomization, with a higher proportion of subjects achieving abstinence among those classified as abstinent for >2 versus ≤2 consecutive weeks prior to randomization (66% vs. 29%). The final tree for predicting no heavy drinking days in the last 4 weeks of treatment had three splits based on consecutive days abstinent, age, and total Alcohol Dependence Scale score at baseline. Seventy-three percent of the subjects classified as abstinent for >2 consecutive weeks prior to randomization had no heavy drinking days in the last 4 weeks of treatment. Among those classified as abstinent ≤2 consecutive weeks prior, three additional splits showed that younger subjects (age ≤44 years; 37%), and older subjects (age >44) with a total Alcohol Dependence Scale score >13 and complete abstinence (56%) or other drinking goals (35%), were less likely to have no heavy drinking days than older subjects with a total Alcohol Dependence Scale score ≤13 (67%). The final tree for predicting a 2-level reduction in WHO levels had no splits. Consecutive days abstinent prior to randomization may predict abstinence and no heavy drinking days and total Alcohol Dependence Scale score and age may predict no heavy drinking days. The 2-level reduction in WHO levels outcome may be less likely to discriminate based on multiple patient characteristics.

Comparison of food cue reactivity and eating behaviours in obesity, ex-smokers and abstinent alcohol dependence.

Comparison of food cue reactivity and eating behaviours in obesity, ex-smokers and abstinent alcohol dependence.

P.021 Comparison of food cue reactivity, eating behaviours, mood and impulsivity in obesity, ex-smokers and abstinent alcohol dependence

A curious correspondence has been known between Landau models and non-linear sigma models: Reinterpreting the base-manifolds of Landau models as field manifolds, the Landau models are transformed to non-linear sigma models with same global and local symmetries. With the idea of the dimensional hierarchy of higher dimensional Landau models, we exploit this correspondence to present a systematic procedure for construction of non-linear sigma models in higher dimensions. We explicitly derive O(2k+1) non-linear sigma models in 2k dimension based on the parent tensor gauge theories that originate from non-Abelian monopoles. The obtained non-linear sigma models turn out to be Skyrme-type non-linear sigma models with O(2k) local symmetry. Through a dimensional reduction of Chern-Simons tensor field theories, we also derive Skyrme-type O(2k) non-linear sigma models in 2k−1 dimension, which realize the original and other Skyrme models as their special cases. As a unified description, we explore Skyrme-type O(d+1) non-linear sigma models and clarify their basic properties, such as stability of soliton configurations, scale invariant solutions, and field configurations with higher winding number.

Comparison of food cue reactivity and eating behaviours in obesity, ex-smokers and abstinent alcohol dependence

Comparison of food cue reactivity and eating behaviours in obesity, ex-smokers and abstinent alcohol dependence

Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals

Addiction has been proposed as a ‘reward deficient’ state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.

A Comparative Study of Factors Associated with Relapse in Alcohol Dependence and Opioid Dependence.

Background:Alcohol and opiates are among the most addictive substances posing significant public health problems due to the biopsychosocial impact that they have on individuals. Research shows that majority of abstinent alcohol and/or opioid dependence subjects relapse within 1 year. It has also been estimated that 26–36 million people worldwide abuse opiates, with exceptionally high-relapse rates. The purpose of this study was to compare the sociodemographic factors and correlates relapse in alcohol dependence and opioid dependence.Methodology:This research uses a cross-sectional comparative study design with a sample size of 60 drawn from a population of clinically diagnosed patients of alcohol dependence (n = 30) or opioid dependence (n = 30) and seeking treatment for relapse. In addition to collecting sociodemographic data, other factors such as craving, affect, self-efficacy, and expressed emotions were measured using standardized instruments including brief substance craving scale, Bradburn affect balance scale, drug avoidance and self-efficacy scale and family emotional involvement, and conflict scale. The data were statistically analyzed.Results:Disparity in sociodemographic factors was seen in both the groups with opioid group being more likely to be single, unemployed, belonging to lower socioeconomic status, and having a criminal record (P = 0.025). Among factors associated with relapse, the opioid group scored significantly higher on craving, perceived criticism (P = 0.0001), and lower on self-efficacy (P = 0.016). Most common reason cited for relapse in both the groups was desire for positive mood.Conclusion:This study highlights the role of social determinants in drug dependence and relapse. Relapse was found to be a complex multifactorial phenomenon. Despite differences in presentation, somewhat similar relapse mechanisms were seen in both groups.

Blunted amygdala functional connectivity during a stress task in alcohol dependent individuals: A pilot study

BackgroundScant research has been conducted on neural mechanisms underlying stress processing in individuals with alcohol dependence (AD). We examined neural substrates of stress in AD individuals compared with controls using an fMRI task previously shown to induce stress, assessing amygdala functional connectivity to medial prefrontal cortex (mPFC). Materials and methodsFor this novel pilot study, 10 abstinent AD individuals and 11 controls completed a modified Trier stress task while undergoing fMRI acquisition. The amygdala was used as a seed region for whole-brain seed-based functional connectivity analysis. ResultsAfter controlling for family-wise error (p = 0.05), there was significantly decreased left and right amygdala connectivity with frontal (specifically mPFC), temporal, parietal, and cerebellar regions. Subjective stress, but not craving, increased from pre-to post-task. ConclusionsThis study demonstrated decreased connectivity between the amygdala and regions important for stress and emotional processing in long-term abstinent individuals with AD. These results suggest aberrant stress processing in individuals with AD even after lengthy periods of abstinence.

Using [11C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism

The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [11C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [11C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [11C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [11C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n=12) underwent an [11C]Ro15 4513 PET scan and compared with matched healthy controls (n=13). We found a significant reduction in [11C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [11C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [11C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [11C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates.

Gender effects in alcohol dependence: an fMRI pilot study examining affective processing.

Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing. Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping. Fearful Condition-The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition-AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals. Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing.

Neural substrates of impulsive decision making modulated by modafinil in alcohol-dependent patients.

Impulsive decision making is a hallmark of frequently occurring addiction disorders including alcohol dependence (AD). Therefore, ameliorating impulsive decision making is a promising target for the treatment of AD. Previous studies have shown that modafinil enhances cognitive control functions in various psychiatric disorders. However, the effects of modafinil on delay discounting and its underlying neural correlates have not been investigated as yet. The aim of the current study was to investigate the effects of modafinil on neural correlates of impulsive decision making in abstinent AD patients and healthy control (HC) subjects. A randomized, double-blind, placebo-controlled, within-subjects cross-over study using functional magnetic resonance imaging (fMRI) was conducted in 14 AD patients and 16 HC subjects. All subjects participated in two fMRI sessions in which they either received a single dose of placebo or 200mg of modafinil 2h before the session. During fMRI, subjects completed a delay-discounting task to measure impulsive decision making. Modafinil improved impulsive decision making in AD pateints, which was accompanied by enhanced recruitment of frontoparietal regions and reduced activation of the ventromedial prefrontal cortex. Moreover, modafinil-induced enhancement of functional connectivity between the superior frontal gyrus and ventral striatum was specifically associated with improvement in impulsive decision making. These findings indicate that modafinil can improve impulsive decision making in AD patients through an enhanced coupling of prefrontal control regions and brain regions coding the subjective value of rewards. Therefore, the current study supports the implementation of modafinil in future clinical trials for AD.

Behavioral and neuroimaging evidence for overreliance on habit learning in alcohol-dependent patients

Substance dependence is characterized by compulsive drug-taking despite negative consequences. Animal research suggests an underlying imbalance between goal-directed and habitual action control with chronic drug use. However, this imbalance, and its associated neurophysiological mechanisms, has not yet been experimentally investigated in human drug abusers. The aim of the present study therefore was to assess the balance between goal-directed and habit-based learning and its neural correlates in abstinent alcohol-dependent (AD) patients. A total of 31 AD patients and 19 age, gender and education matched healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during completion of an instrumental learning task designed to study the balance between goal-directed and habit learning. Task performance and task-related blood oxygen level-dependent activations in the brain were compared between AD patients and healthy matched controls. Findings were additionally associated with duration and severity of alcohol dependence. The results of this study provide evidence for an overreliance on stimulus-response habit learning in AD compared with HC, which was accompanied by decreased engagement of brain areas implicated in goal-directed action (ventromedial prefrontal cortex and anterior putamen) and increased recruitment of brain areas implicated in habit learning (posterior putamen) in AD patients. In conclusion, this is the first human study to provide experimental evidence for a disturbed balance between goal-directed and habitual control by use of an instrumental learning task, and to directly implicate cortical dysfunction to overreliance on inflexible habits in AD patients.

S15 * ALCOHOL DEPENDENCE AND NEUROENDOCRINOLOGY - NEW FINDINGS AND PERSPECTIVES

S15 * ALCOHOL DEPENDENCE AND NEUROENDOCRINOLOGY - NEW FINDINGS AND PERSPECTIVES

Disrupted Ventromedial Prefrontal Function, Alcohol Craving, and Subsequent Relapse Risk

Alcohol dependence is a chronic relapsing illness; stress, alcohol-related cues, and neutral-relaxing states significantly influence craving and relapse risk. However, neural mechanisms underlying the association between these states and alcohol craving and relapse risk remain unclear. To identify neural correlates associated with alcohol craving and relapse outcomes in 45 treatment-engaged, 4- to 8-week abstinent alcohol-dependent (AD) patients, and to compare brain responses of 30 demographically matched AD patients and 30 healthy control subjects during stress, alcohol, and neutral-relaxing cues. Functional magnetic resonance imaging study while participants were engaging in brief individualized script-driven imagery trials of stress, alcohol cues, and neutral-relaxing scenarios, and a prospective clinical outcome design to assess alcohol relapse 90 days postdischarge from inpatient treatment in the AD group. Inpatient treatment setting in a community mental health center and hospital-based research unit. Forty-five recovering AD patients in inpatient treatment for examining relapse, and 30 healthy control subjects demographically matched to 30 AD patients (subgroup of the relapse sample) for group comparisons. Twelve-step recovery-based addiction treatment for the patient group. Brain response, alcohol craving, and relapse outcome measures (time to relapse and relapse severity). Increased ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) activation during neutral-relaxing trials was correlated with high alcohol cue-induced and stress-induced craving in early recovering AD patients (x = 6, y = 43, z = -6; P < .01, whole-brain corrected). This vmPFC/ACC hyperactivity significantly predicted subsequent alcohol relapse, with a hazards ratio greater than 8 for increased relapse risk. Additionally, vmPFC/ACC hyperactivation during neutral trials and reduced activity during stress trials were each predictive of greater days of alcohol used after relapse (P < .01, whole-brain corrected). In contrast, matched control subjects showed the reverse pattern of vmPFC/ACC responses to stress, alcohol cues, and relaxed trials (F = 6.42; P < .01, whole-brain corrected). Findings indicate that disrupted vmPFC/ACC function plays a role in jeopardizing recovery from alcoholism and may serve as a neural marker to identify those at risk for alcohol relapse.

Influence of OPRM1 Asn40Asp variant (A118G) on [11C]carfentanil binding potential: preliminary findings in human subjects

The Asn40Asp variant (A118G) of the μ opioid receptor (OPRM1) gene is thought to contribute to the development and treatment of alcohol dependence. Employing positron emission tomography (PET), we first examined whether the single nucleotide polymorphism (SNP) modifies binding potential (BP(ND)) of the μ-selective ligand [(11)C]carfentanil in healthy control (Con) and 5-d abstinent alcohol-dependent (AD) subjects (unblocked basal scan). Second, we examined whether the allelic variants were associated with differences in OPRM1 occupancy by naltrexone (50 mg) in AD subjects. Con and AD carriers of the G allele (AG) had lower global BP(ND) at the basal scan than subjects homozygous for the A allele (AA). In AD subjects, naltrexone occupancy was slightly higher in AG subjects (98.9%) compared to AA subjects (93.1%), but this was not significant. We are the first to demonstrate using PET in healthy normal and AD subjects that the A118G SNP alters OPRM1 availability.

The relationship between impulsivity and craving in alcohol dependent patients

Impulsivity and craving are both associated with higher relapse rates and a worse prognosis in patients with a substance use disorder, but the relationship between these two phenomena has been largely ignored in the field of alcohol use disorders. The primary aim of this study was to investigate the relationship between different dimensions of impulsivity and different forms of self-reported craving. Additionally, the influence of the severity of alcohol dependence on impulsivity, craving, and on their relationship was exploed. Impulsivity and craving levels were investigated in 87 abstinent alcohol-dependent (AD) patients using a broad range of self-report questionnaires and behavioral impulsivity measures. Alcohol use was measured by means of the timeline followback method. Higher scores of emotional craving (Alcohol Urge Questionnaire-AUQ) were significantly related to higher self-reported impulsivity (Barratt Impulsiveness Scale, version 11) and to higher cognitive impulsivity (information sampling task). Additionally, exploratory analyses suggest that these relationships are more pronounced in severe AD patients compared to less severe AD patients. No significant relationships were found between emotional craving (AUQ) and motor impulsivity (stop signal task) or delay discounting and between obsessive-compulsive craving (Obsessive Compulsive Drinking Scale) and measures of impulsivity. Emotional craving is related to self-reported impulsivity and to cognitive impulsivity. These relationships seem to be more pronounced in AD patients with severe alcohol dependence. Further research is needed to explore the effect of this relationship on treatment outcome and relapse.

Antisocial Symptoms Decrease to Normal Levels in Long‐Term Abstinence

We have previously shown highly elevated antisocial symptoms and measures of social deviance proneness and antisocial disposition in long-term abstinent alcohol dependence versus non-substance-abusing controls (NSAC). Current antisocial symptoms were reduced to subdiagnostic levels in long-term abstinence; however, the number of current symptoms was not measured beyond its being subdiagnostic. Here we measured social deviance proneness, antisocial disposition, and both lifetime and current antisocial symptoms in short-term and long-term abstinent substance-dependent and NSAC samples. Lifetime antisocial symptoms (and diagnoses) and social deviance proneness and antisocial disposition were highly elevated in both short- and long-term abstinence, replicating earlier findings. Current antisocial symptoms were dramatically reduced in long-term versus short-term abstinent samples, close to levels in controls. In contrast, social deviance proneness and antisocial disposition remain highly elevated in long-term abstinence. These findings suggest that antisocial behavior is reduced in extended abstinence, despite continued elevated social deviance proneness an antisocial disposition. This suggests a top-down model in extended abstinence, whereby executive control inhibits deviance-prone tendencies.

Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers

Although the effects of alcohol on brain-derived neurotrophic factor (BDNF) have been extensively studied in rodents, BDNF levels have rarely been measured in abstinent, alcohol-dependent (AD) individuals. Interpretation of reported group comparisons of serum BDNF levels is difficult due to limited information regarding analytical variance, biological variability, and the relative contribution of platelet and plasma pools to serum BDNF. Analytical variance (intra- and inter-assay coefficients of variation) of the enzyme-linked immunosorbent assay (ELISA) was characterized. Within- and between-subject variability, and group differences in serum and plasma BDNF, was assessed on three separate days in 16, 4-week abstinent AD individuals (7M/9F) and 16 social drinkers (SDs; 8M/8F). Significantly higher mean (±sd) serum BDNF levels were observed for the AD group compared to the SD (p = 0.003). No significant difference in mean baseline plasma BDNF levels was observed between AD and SD groups. The low analytical variance, high day-to-day within-individual stability and the high degree of individuality demonstrates the potential clinical utility of measuring serum BDNF levels. The low correlations that we observed between plasma and serum levels are congruent with their representing separate pools of BDNF. The observation of higher basal serum BDNF in the AD group without a concomitant elevation in plasma BDNF levels indicates that the elevated serum BDNF in AD patients is not due to greater BDNF exposure. Further research is warranted to fully elucidate mechanisms underlying this alteration and determine the utility of serum BDNF as a predictor or surrogate marker of chronic alcohol abuse.

Cognitive-behavioral therapy for insomnia in alcohol dependent patients: A randomized controlled pilot trial

In a randomized controlled trial, we evaluated the efficacy of cognitive-behavioral treatment for insomnia to improve sleep and daytime symptoms, and to reduce relapse in recovering alcohol dependent (AD) participants. Seventeen abstinent AD patients with insomnia (6 women, mean age 46.2 ± 10.1 years) were randomized to 8 sessions of cognitive-behavioral treatment for insomnia for AD (CBTI-AD, n = 9) or to a behavioral placebo treatment (BPT, n = 8). Subjective measures of sleep, daytime consequences of insomnia and AD, alcohol use, and treatment fidelity were collected at baseline and post-treatment. Diary-rated sleep efficiency and wake after sleep onset, and daytime ratings of General Fatigue on the Multidimensional Fatigue Inventory improved more in the CBTI-AD compared to the BPT group. In addition, more subjects were classified as treatment responders following CBTI-AD. No group differences were found in the number of participants who relapsed to any drinking or who relapsed to heavy drinking. The findings suggest that cognitive-behavioral insomnia therapy benefits subjective sleep and daytime symptoms in recovering AD participants with insomnia more than placebo. The benefits of treating insomnia on drinking outcomes are less apparent.

Smoking history, nicotine dependence, and changes in craving and mood during short-term smoking abstinence in alcohol dependent vs. control smokers

ObjectiveThe goal of this study was to compare lifetime cigarette smoking, severity of nicotine dependence, and subjective effects of short-term tobacco abstinence in abstinent alcohol dependent (AD) and control smokers. MethodAD (n=119) and control (n=55) ever-smokers were compared on tobacco use history and nicotine dependence. Negative affect and craving to smoke were examined in a subsample of currently smoking AD (N=34) and control (N=19) participants during a 6-h period of tobacco abstinence using the Profile of Mood States (POMS) and the Questionnaire on Smoking Urges-Brief (QSU-B). ResultsAlthough AD smokers did not differ from controls on heaviness of smoking, they were more likely to meet lifetime criteria for nicotine dependence. AD smokers also reported more withdrawal symptoms and were more likely to endorse withdrawal-related depressed mood during past smoking reduction or abstinence periods. During short-term abstinence, AD smokers were more likely to report high craving to smoke for negative affect relief within the first 150min of tobacco abstinence, but did not differ from controls on overall craving to smoke or withdrawal-related negative affect on the POMS. ConclusionsResults support previous findings that AD smokers have a greater prevalence of nicotine dependence and more severe nicotine withdrawal, with a greater propensity toward withdrawal-related depressed mood. These results, along with our novel finding that greater craving to smoke in abstaining smokers with AD is specific to negative affect-related craving, suggest that negative reinforcement may be a particularly salient factor in the maintenance of tobacco use among individuals with AD.