Lisa Fucito

The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in Alzheimer's disease and other degenerative conditions. Numerous animal studies described cholinergic and non-cholinergic neuronal responses in the BNM; however, work in humans has been hampered by the difficulty of defining the BNM anatomically. Here, on the basis of a previous study that delineated the BNM of post-mortem human brains in a standard stereotaxic space, we sought to examine functional connectivity of the BNM, as compared to the nucleus accumbens (or ventral striatum, VS), in a large resting state functional magnetic resonance imaging data set. The BNM and VS shared but also showed a distinct pattern of cortical and subcortical connectivity. Compared to the VS, the BNM showed stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and midbrain, as well as the anterior cingulate cortex, ...

Continued high alcohol consumption levels by college students highlight the need for more effective alcohol interventions and novel treatment engagement strategies. The purpose of this study was to investigate a behavioral sleep intervention as a means to engage heavy-drinking college students in treatment and reduce alcohol use and alcohol-related consequences. Heavy-drinking college students (N = 42) were assigned to 1 of 2 web-based interventions comprised of 4 modules delivered over 4 weeks. The experimental intervention focused primarily on sleep and included evidence-based sleep content (i.e., stimulus control instructions, sleep scheduling [consistent bed/rise times; ideal sleep duration for adolescents/young adults], sleep hygiene advice, relaxation training, cognitive strategies to target sleep-disruptive beliefs), and alcohol content (i.e., normative and blood alcohol level feedback, moderate drinking guidelines, controlled drinking strategies, effects of alcohol on sleep and the body, advice to moderate drinking for improved sleep) in young adults. The control condition Healthy Behaviors provided basic advice about nutrition, exercise, sleep (i.e., good sleep hygiene only), and drinking (i.e., effects of alcohol on the body, moderate drinking guidelines, advice to moderate drinking for sleep). Participants in both conditions monitored their sleep using daily web-based diaries and a wrist-worn sleep tracker. Recruitment ads targeting college students with sleep concerns effectively identified heavy-drinking students. The program generated a high number of inquiries and treatment completion rates were high. Both interventions significantly reduced typical week drinking and alcohol-related consequences and improved sleep quality and sleep-related impairment ratings. The control condition yielded greater reductions in total drinks in a heaviest drinking week. The effects on drinking were larger than those observed in typical brief alcohol intervention studies for college students. Greater sleep improvement tended to predict better subsequent drinking outcomes. The results suggest that sleep treatment may be a promising strategy for targeting and treating heavy-drinking college students.

Heavy drinking among young adults is a serious public health problem. Naltrexone, an opioid antagonist, has been shown to reduce drinking in young adults compared to placebo and can be taken on a targeted (i.e., as needed) basis. Understanding risk factors for drinking and naltrexone effects within-person in young adults may help to optimize the use of targeted naltrexone. The current study was a secondary analysis of daily diary data from 127 (n = 40 female) young adults (age 18-25) enrolled in a double-blind clinical trial of daily (25 mg) plus targeted (25 mg) naltrexone versus placebo. Hierarchical linear models were used to examine the effects of daily affect, urge, and taking targeted medication on same-day risk of drinking to intoxication (defined as estimated blood-alcohol-concentration, BAC ≥ .08 g%). Results indicated urge significantly mediated within-person positive affect-drinking relations on a daily level. Specifically, positive affect was associated with greater urge...

Young adults with higher trait urgency (i.e., a tendency to act rashly in response to heightened affect) may be especially vulnerable to heavy drinking. The current study examined 1) the influence of urgency on daily relations between affect and drinking to intoxication, and 2) whether urgency influenced the effectiveness of naltrexone (vs. placebo) for reducing alcohol use. This study is a secondary analysis of data from 126 (n=40 female) heavy drinking young adults, ages 18-25, enrolled in a double-blind, 8-week clinical trial comparing brief motivational intervention and either naltrexone or placebo. Multilevel models examined whether trait urgency moderated daily relations between positive and negative affect and drinking to intoxication, measured by an estimated blood-alcohol concentration (eBAC) at or above the legal limit (≥0.08g%). Person-level interactions examined whether naltrexone was more effective than placebo at reducing the odds of eBAC≥0.08g% for individuals with hi...

Male sexuality in adolescence and early adulthood is characterized by autonomous, predictable erections. As males age, however, their arousal becomes less predictable and more dependent on partner interaction. This transition can produce anxiety. Many males view this change as a medical dysfunction requiring pharmacologic treatment or specialist intervention. New medical interventions, including Viagra, have been developed promising to return males to their automatic erections. A medical approach, however, fails to address the multidimensional nature of male sexuality and reinforces sex as intercourse performance. This article outlines a biopsychosocial approach to the assessment, treatment, and relapse prevention of male sexual dysfunction.

Smoking cessation is crucial for reducing cancer risk and premature mortality. The US Preventive Services Task Force (USPSTF) has recommended annual lung cancer screening with low-dose computed tomography (LDCT), and the Center for Medicare and Medicaid Services recently approved lung screening as a benefit for patients ages 55 to 77 years who have a 30 pack-year history. The Society for Research on Nicotine and Tobacco (SRNT) and the Association for the Treatment of Tobacco Use and Dependence (ATTUD) developed the guideline described in this commentary based on an illustrative literature review to present the evidence for smoking-cessation health benefits in this high-risk group and to provide clinical recommendations for integrating evidence-based smoking-cessation treatment with lung cancer screening. Unfortunately, extant data on lung cancer screening participants were scarce at the time this guideline was written. However, in this review, the authors summarize the sufficient evidence on the benefits of smoking cessation and the efficacy of smoking-cessation interventions for smokers ages 55 to 77 years to provide smoking-cessation interventions for smokers who seek lung cancer screening. It is concluded that smokers who present for lung cancer screening should be encouraged to quit smoking at each visit. Access to evidence-based smoking-cessation interventions should be provided to all smokers regardless of scan results, and motivation to quit should not be a necessary precondition for treatment. Follow-up contacts to support smoking-cessation efforts should be arranged for smokers. Evidence-based behavioral strategies should be used at each visit to motivate smokers who are unwilling to try quitting/reducing smoking or to try evidence-based treatments that may lead to eventual cessation. Cancer 2016;122:1150-9. © 2016 American Cancer Society.

Stress and anxiety have been shown to increase smoking motivation. There is limited experimental data on depressed or sad mood and smoking. This study investigated the effects of two induced moods on smoking behavior. Depression scores were examined as a potential moderator and mood changes were tested as a potential mediator. Smokers (N = 121) were randomly assigned to receive either a sad induction or a neutral induction via standardized film clips. Among participants with higher depression scores, smoking duration and the number of cigarette puffs were greater in response to the sad condition. There was also a marginal interactive effect on the change in expired air carbon monoxide among this subsample; however, no differences in smoking latency or craving were observed. Changes in positive mood partially mediated the effect of condition on smoking behavior among participants with high depression scores. There was no modifying effect of gender or mediating effect of negative mood changes. The results provide preliminary support that decreases in positive mood may have a greater influence on smoking behavior among depression-prone smokers than less psychiatrically vulnerable smokers.

Behavioral interventions for young adults show limited effects 1-year posttreatment. Few studies have examined the longitudinal outcomes of pharmacotherapy trials to reduce heavy drinking. This study examined the posttreatment, longitudinal effects of the first placebo-controlled trial of naltrexone in young adult heavy drinkers. Randomized, double-blind, placebo-controlled, 8-week trial. Follow-up assessments at posttreatment (8 weeks [8W]), 3 months [3M], 6 months [6M], and 12 months [12M]). Participants were young adults ages 18-25 (N = 118) who reported ≥4 heavy drinking days in the prior 4 weeks. Outcomes were percent days heavy drinking (PHDD), percent days abstinent (PDA), and drinks per drinking day (DPDD). There were no time effects on PHDD. Treatment improvements were maintained posttreatment. A main effect of time was found for PDA. Both conditions continued to increase PDA posttreatment. For DPDD, a Treatment ×Time interaction emerged. In the naltrexone condition, DPDD i...

Neuroimaging studies have dramatically advanced our understanding of the neurochemical basis of alcohol dependence, a major public health issue. In this paper, we review the research generated from neurochemical specific imaging modalities including magnetic resonance spectroscopy, positron emission tomography, and single-photon emission computed tomography in studies of alcohol dependence and withdrawal. We focus on studies interrogating γ-aminobutyric acid (GABA), glutamate, and dopamine, as these are prominent neurotransmitter systems implicated in alcohol dependence. Highlighted findings include diminished dopaminergic functioning and modulation of the GABA system by tobacco smoking during alcohol withdrawal. Then, we consider how these findings impact the clinical treatment of alcohol dependence and discuss directions for future experiments to address existing gaps in the literature, for example, sex differences and smoking comorbidity. These and other considerations provide op...

Cigarette smoking creates a substantial public health burden. Identifying new, effective smoking cessation interventions that optimize existing interventions and promoting effective use of approved medications is a priority. When used as directed, nicotine replacement therapy (NRT) aids smoking cessation, but there is opportunity for improving its effectiveness. Until recently, NRT use guidelines advised smokers to begin using NRT on their quit date, only to use 1 NRT formulation at a time, to refrain from using NRT while smoking, and to stop NRT within 3 months regardless of progress. The Food and Drug Administration (FDA) issued a recent announcement allowing for NRT labeling changes with applications from pharmaceutical companies for such changes, and we applaud this decision. Nevertheless, additional revisions are warranted by current research. There is robust evidence that combining a longer-acting form (e.g., patch) with a shorter-acting form (e.g., lozenge) is more effective ...

The goal of the current study was to use tree-based methods (Zhang and Singer, 2010, Recursive Partitioning and Applications, 2nd ed. Springer, New York) to identify predictors of abstinence from heavy drinking in COMBINE (Anton et al. JAMA 2006; 295:2003), the largest study of pharmacotherapy for alcoholism in the United States to date, and to validate these results in PREDICT (Mann et al. Addict Biol 2012; 18:937), a parallel study conducted in Germany. We compared a classification tree constructed according to purely statistical criteria to a tree constructed according to a combination of statistical criteria and clinical considerations for prediction of no heavy drinking during treatment in COMBINE. We considered over 100 baseline predictors. The tree approach was compared to logistic regression. The trees and a deterministic forest identified the most important predictors of no heavy drinking for direct testing in PREDICT. The tree built using both clinical and statistical considerations consisted of 4 splits based on consecutive days of abstinence (CDA) prior to randomization, age, family history of alcoholism, and confidence to resist drinking in response to withdrawal and urges. The tree based on statistical considerations with 4 splits also split on CDA and age but also on gamma-glutamyl transferase level and drinking goal. Deterministic forest identified CDA, age, and drinking goal as the most important predictors. Backward elimination logistic regression among the top 18 predictors identified in the deterministic forest analyses identified only age and CDA as significant main effects. Longer CDA and goal of complete abstinence were associated with better outcomes in both data sets. The most reliable predictors of abstinence from heavy drinking were CDA and drinking goal. Trees provide binary decision rules and straightforward graphical representations for identification of subgroups based on response and may be easier to implement in clinical settings.

Introduction:Smokers’ treatment expectancies may influence their choice of a particular medication as well as their medication experience.Aims:This study examined the role of smokers’ treatment expectancies to their smoking cessation outcomes in a completed, randomized, placebo-controlled trial of naltrexone for smoking cessation, controlling for perceptions of treatment assignment.Methods:Treatment-seeking cigarette smokers (N= 315) were randomized to receive either naltrexone (50 mg) or placebo in combination with nicotine patch and behavioural counselling. Expectancies for naltrexone as a smoking cessation aid were assessed at baseline and four weeks after the quit date.Results:More positive baseline medication expectancies predicted higher quit rates at one month in the naltrexone group (OR = 1.45,p= 0.04) but were associated with lower quit rates in the placebo group (OR = 0.66,p= 0.03). Maintaining and/or increasing positive medication expectancies in the first month of treatm...

Stress and anxiety have been shown to increase smoking motivation. There is limited experimental data on depressed or sad mood and smoking. This study investigated the effects of two induced moods on smoking behavior. Depression scores were examined as a potential moderator and mood changes were tested as a potential mediator. Smokers (N = 121) were randomly assigned to receive either a sad induction or a neutral induction via standardized film clips. Among participants with higher depression scores, smoking duration and the number of cigarette puffs were greater in response to the sad condition. There was also a marginal interactive effect on the change in expired air carbon monoxide among this subsample; however, no differences in smoking latency or craving were observed. Changes in positive mood partially mediated the effect of condition on smoking behavior among participants with high depression scores. There was no modifying effect of gender or mediating effect of negative mood changes. The results provide preliminary support that decreases in positive mood may have a greater influence on smoking behavior among depression-prone smokers than less psychiatrically vulnerable smokers.

Negative affect is an important psychological factor in the promotion and maintenance of cigarette smoking, though the underlying factors that account for this relationship remain to be determined. One possible mechanism may be smokers' emotion regulation strategies. Preliminary research among adolescents and young adults suggests that greater utilization of expressive suppression versus cognitive reappraisal is associated with higher rates of smoking initiation. There is limited research, however, on the role of emotion regulation strategies in smoking maintenance in adult smokers. Data from participants in a laboratory study (N = 121) were used to examine whether utilization of cognitive reappraisal and/or expressive suppression were related to smoking characteristics and subjective (i.e., mood, urge to smoke ratings) and behavioral reactions (i.e., Emotional Stroop Task performance, smoking behavior) to a mood induction procedure. Data were evaluated for the full sample and subsample who endorsed current depressive symptoms (n = 46). Frequent reappraisal was associated with weaker expectancies that smoking alleviates unpleasant feelings, greater positive mood, and fewer depressive symptoms. In contrast, frequent suppression was related to longer smoking history and greater attentional bias to smoking cues on an Emotional Stroop Task. Among the depressed subsample, reappraisal moderated the effect of mood condition on smoking duration, number of cigarette puffs, and carbon monoxide boost. These results provide preliminary support that emotion regulation strategies may be associated with motivational correlates of smoking as well as actual smoking behavior among depressed smokers.

Male sexuality in adolescence and early adulthood is characterized by autonomous, predictable erections. As males age, however, their arousal becomes less predictable and more dependent on partner interaction. This transition can produce anxiety. Many males view this change as a medical dysfunction requiring pharmacologic treatment or specialist intervention. New medical interventions, including Viagra, have been developed promising to return males to their automatic erections. A medical approach, however, fails to address the multidimensional nature of male sexuality and reinforces sex as intercourse performance. This article outlines a biopsychosocial approach to the assessment, treatment, and relapse prevention of male sexual dysfunction.

Alcohol consumption is associated with smoking cessation failure in both community and clinical research. However, little is known about the relation between alcohol consumption and smoking cessation milestones (i.e., achieving initial abstinence, avoiding lapses and relapse). Our objective in this research was to examine the relations between pretreatment alcohol consumption patterns (non/infrequent drinker, moderate drinker, binge drinker) and smoking cessation milestones and tobacco dependence. Data were collected from 1,504 smokers (58.2% women; 83.9% White; mean age = 44.67 years, SD = 11.08) making an aided smoking cessation attempt as part of a clinical trial. Alcohol consumption pattern was determined with the Composite International Diagnostic Interview. Tobacco dependence was assessed with the Wisconsin Inventory of Smoking Dependence Motives (WISDM). Alcohol consumption pattern was significantly associated with initial cessation and lapse, and these findings remained after controlling for the effects of treatment, race, gender, and cigarettes per day. Relative to moderate drinkers, both non/infrequent drinkers and binge drinkers were less likely to achieve initial cessation (p < .05), and binge drinkers were more likely to lapse (p < .01). When drinking categories were compared on tobacco dependence indices, results showed that relative to moderate drinkers, non/infrequent drinkers scored higher on several WISDM Primary Dependence Motives subscales (Tolerance, Loss of Control, and Automaticity) and binge drinkers scored higher on WISDM Secondary Dependence Motives subscales (Cue Exposure and Social-Environmental Goads). Non/infrequent drinkers' smoking cessation difficulties may be particularly related to core features of tobacco dependence, whereas binge drinkers' difficulties may be related to environmental and social influences.

Illnesses that are caused by smoking remain as the world's leading cause of preventable death. Smoking and tobacco use constitute approximately 30% of all cancer-related deaths and nearly 90% of lung cancer-related deaths. Thus, improving smoking cessation interventions is crucial to reduce tobacco use and assist in minimizing the burden of cancer and other diseases in the United States. This review focuses on the existing research on framed messages to promote smoking cessation. Consistent with the tenets of prospect theory and recent meta-analysis, gain-framed messages emphasizing the benefits of quitting seem to be preferable when working with adult patients who smoke tobacco products. The evidence also suggests that moderators of treatment should guide framed statements made to patients. Meta-analyses have provided consistent moderators of treatment such as need for cognition, but future studies should further define the specific framed interventions that would be most helpful for subgroups of smokers. In conclusion, instead of using loss-framed statements like "Smoking will harm your health by causing problems like lung and other cancers, heart disease, and stroke," as a general rule, physicians should use gain-framed statements like "Quitting smoking will benefit your health by preventing problems like lung and other cancers, heart disease, and stroke."

The goal of the current study was to use tree-based methods to identify moderators of acamprosate effect on abstinence from heavy drinking in COMBINE, the largest study of pharmacotherapy for alcoholism in the United States to date. We used three different tree-based methods for identification of subgroups with enhanced treatment response on acamprosate based on over 100 predictors measured at baseline in COMBINE. No heavy drinking during the last two months of treatment was the considered outcome. All three methods identified consecutive days of abstinence prior to treatment as the most important moderator of treatment effect. Acamprosate was beneficial for participants with shorter abstinence (1 week or less) especially when body mass index was low or normal. In this group, 46% of participants receiving active acamprosate abstained from heavy drinking compared to 23% of those receiving placebo acamprosate. Prior treatment, age, drinking goal and cognitive inefficiency were identified as moderators of acamprosate effects by one of the three methods. In conclusion, acamprosate may be beneficial for participants with shorter abstinence who are not overweight or obese. One hypothesis for this finding is that this subgroup may have greater glutamatergic hyperactivity, a target of acamprosate, and may achieve better drug plasma levels based on their lower BMI. In contrast, those with extended pretreatment abstinence who have anotherwise good prognosis did not benefit from acamprosate. Further validation of the results in independent data sets is necessary.

Achieving high protocol adherence is essential for ensuring the overall success and scientific merit of clinical trials. Strategies for maximizing recruitment and treatment adherence have been previously explored in the literature. There has been less focus, however, on effective methods for maintaining participants in research follow-up. This article examines factors associated with poor follow-up rates as well as strategies for facilitating research commitment and addressing sources of nonadherence. Special attention is devoted to alcohol- and substance-dependent populations, groups known to have poor adherence rates. Examples are drawn from the COMBINE Study, an NIAAA-funded, nationwide, multisite, combined behavioral and pharmacotherapy trial for alcohol problems that achieved high one-year follow-up rates. The important role of coordinating centers in facilitating research retention is also discussed.

There is consistent evidence that the binge drinking standard of 5+ drinks per drinking occasion for men (4+ for women) is associated with risk for negative consequences. Yet, many have questioned the adequacy of this measure as an index of intoxication (e.g., a blood alcohol concentration [BAC] of 0.08 g%). In response to these concerns, a National Institute on Alcohol Abuse and Alcoholism task force recommended adding a time qualifier of 2 hours to this criterion. Although conceptually appealing, there has been little effort to determine whether this new measure better captures drinking that leads to negative consequences. This study examined the new binge standard (2-hour period) and old binge standard (no time qualifier) in relation to frequency of drinking to an estimated BAC of 0.08 g% and the experience of negative drinking consequences. These relations were examined within both a social drinking sample of adults (N = 200) and a sample of heavy-drinking young adults (N = 168)...

Sleep disturbance and heavy drinking increase risk of negative consequences in college students. Limited research exists on how they act synergistically, and the overall nature of sleep and sleep-related impairment in college student drinkers is poorly understood. A latent profile analysis was conducted on the sleep characteristics and daytime sleep-related consequences of college student drinkers who were at-risk based on Alcohol Use Disorders Identification Test-Consumption scores. Participants (N = 312, mean age = 18.90 (0.97) years) consumed a mean (SD) of 20.93 (13.04) drinks per week. Scores on the 10 items of the Sleep/Wake Behavior Problems Scale (SWPS) were the class indicators. Four classes best described the sleep and sleep-related consequences of at-risk college drinkers. Classes represented different gradients and types of sleep patterns and sleep-related impairment; nearly half the sample reported late bedtimes and daytime consequences of insufficient sleep. Subsequent...

The purpose of this mixed methods study was to describe the sleep and psychological characteristics of heavy-drinking college students, their perceptions of sleep and sleep/alcohol interactions, and their reactions to a proposed integrated sleep and alcohol Web-based intervention. Students (N = 24) completed standardized surveys and participated in semistructured focus group interviews. Participants reported a high degree of sleep disturbance, sleep obstacles, and sleep-related consequences, which were validated by both quantitative and qualitative investigations. Sleep disturbance and sleep-related impairment were associated with more frequent drinking and greater risks from drinking. Participants perceived that alcohol has positive and negative effects on sleep latency, continuity, and quality. They expressed overall enthusiasm for the intervention but had specific content and format preferences.

Naltrexone, an opioid antagonist, may facilitate reduction in drinking among young adults. We compared the efficacy and safety of naltrexone administered daily plus targeted dosing with placebo to reduce drinking in young adults who engage in heavy drinking. A randomized, double-blind, placebo-controlled study was conducted in an outpatient research center in March 2008-January 2012. Participants were aged 18-25 years and reported ≥ 4 heavy drinking days in the prior 4 weeks. Interventions included naltrexone 25 mg daily plus 25 mg targeted (at most daily) in anticipation of drinking (n = 61) or daily/targeted placebo (n = 67). All participants received a personalized feedback session and brief counseling every other week. Primary outcomes were percent heavy drinking days and percent days abstinent over the 8-week treatment period. Secondary outcomes included number of drinks per drinking day and percentage of days with estimated blood alcohol concentration (BAC) levels ≥ 0.08 g/dL....

Sleep disturbance is common among cigarette smokers and predicts smoking cessation failure. The purpose of this study was to conduct a pilot test of whether provision of a sleep intervention might bolster smoking cessation outcomes among this vulnerable group. Smokers with insomnia (N = 19) seeking smoking cessation treatment were randomly assigned to receive 8 sessions over 10 weeks of either: (1) cognitive-behavioural therapy for insomnia + smoking cessation counselling (CBT-I+SC; n = 9) or (2) smoking cessation counselling alone (SC; n = 10). Counselling commenced 4 weeks prior to a scheduled quit date, and nicotine patch therapy was also provided for 6 weeks starting on the quit date. There was no significant effect of counselling condition on smoking cessation outcomes. Most participants had difficulty initiating and maintaining smoking abstinence in that 7-day point prevalence abstinence rates at end of treatment (CBT-I+SC: 1/7, 14%; SC: 2/10, 20%) and follow-up (CBT-I+SC: 1/7, 14%; SC: 0/10, 0%) were low for both conditions. CBT-I+SC participants reported improvements in sleep efficiency, quality, duration and insomnia symptoms. Sleep changes were not associated with the likelihood of achieving smoking abstinence. This randomised pilot study suggests that behavioural interventions may improve sleep among smokers with insomnia, but a larger sample is needed to replicate this finding and evaluate whether these changes facilitate smoking cessation.