Neuropsychological Trajectories Associated with Adolescent Alcohol and Cannabis Use: A Prospective 14-Year Study.

OBJECTIVES: Alcohol and cannabis remain the substances most widely used by adolescents. Better understanding of the dynamic relationship between trajectories of substance use in relation to neuropsychological functioning is needed. The aim of this study was to examine the different impacts of within- and between-person changes in alcohol and cannabis use on neuropsychological functioning over multiple time points. METHODS: Hierarchical linear modeling examined the effects of alcohol and cannabis use on neuropsychological functioning over the course of 14 years in a sample of 175 adolescents (aged 12-15 years at baseline). RESULTS: Time-specific fluctuations in alcohol use (within-person effect) predicted worse performance across time on the Wechsler Abbreviated Scale of Intelligence Block Design subtest (B = -.05, SE = .02, p = .01). Greater mean levels of percent days of cannabis use across time (between-person effect) were associated with an increased contrast score between Delis-Kaplan Executive Function System Color Word Inhibition and Color Naming conditions (B = .52, SE = .14, p < .0001) and poorer performance over time on Block Design (B = -.08, SE = .04, p = .03). Neither alcohol and/nor cannabis use over time was associated with performance in the verbal memory and processing speed domains. CONCLUSIONS: Greater cumulative cannabis use over adolescence may be linked to poorer inhibitory control and visuospatial functioning performance, whereas more proximal increases in alcohol consumption during adolescence may drive alcohol-related performance decrements in visuospatial functioning. Results from this prospective study add to the growing body of literature on the impact of alcohol and cannabis use on cognition from adolescent to young adulthood.

Effects of sleep on substance use in adolescents: a longitudinal perspective.

Substance use (SU) and sleep problems appear interrelated, but few studies have examined the influence of adolescent sleep patterns on development of SU disorders. This study prospectively examined the influence of sleep habits on subsequent SU in youth who later transitioned into heavy drinking. At time 1 (T1), participants (n = 95) were substance-naive 12- to 14-year-olds. Path-analytic models examined whether the effects of T1 risk factors (familial SU disorder, inhibition control, and externalizing and internalizing traits) on time 3 (M = 19.8 years old) tobacco, alcohol, and cannabis were mediated by time 2 (M = 15.1 years old) sleep chronotype, daytime sleepiness, and erratic sleep/wake behaviors. Significant direct path effects of T1 risk factors and time 2 sleep behaviors on time 3 SU were found, Ps < 0.05. In models that examined the effect of each individual sleep behavior separately on SU, more erratic sleep/wake and greater daytime sleepiness predicted higher lifetime use events for all substances (Ps < 0.01). Higher evening chronotype tendencies predicted lower tobacco and higher alcohol and cannabis lifetime use events (Ps < 0.01). Erratic sleep/wake behaviors mediated the effect of inhibitory control on subsequent SU; less erratic sleep/wake behaviors predicted better inhibition control ( ß̂= -0.20, P < 0.05). Early-mid adolescent psychiatric health and sleep behaviors prior to drinking onset predicted greater SU 5 years later. Participants were substance-naïve at baseline, allowing for the examination of temporal order in the relationship between sleep problems and alcohol use. Early adolescent sleep problems may be an important risk factor for SU in later life.

A Randomized Trial Evaluating Whether Topiramate Aids Smoking Cessation and Prevents Alcohol Relapse in Recovering Alcohol-Dependent Men.

BACKGROUND: Alcohol and nicotine dependence frequently co-occur, and quitting smoking might enhance long-term alcohol abstinence. Topiramate appears to help non-alcohol-dependent individuals quit smoking, and our pilot work suggested efficacy only in men. It also prevents relapse to alcohol in recently detoxified alcoholics. We evaluated topiramate in abstinent alcohol-dependent men to assess whether this medication (i) promotes smoking cessation and (ii) prevents alcohol and other drug relapse in the context of smoking cessation treatment. METHODS: One hundred and twenty-nine alcohol-abstinent (mean ~6 months) alcohol-dependent male smokers (80% with other substance use disorders) participated in this 12-week randomized, double blind, parallel group comparison of topiramate (up to 200 mg/d) and placebo with a 24-week nontreatment follow-up period. The study was carried out sequentially at 2 academic centers in the Midwest and Southern California between March 23, 2009 and November 20, 2014. All participants received manual-guided smoking cessation counseling combined with medication-focused compliance enhancement therapy. Randomization was block designed by the research pharmacist in a 1:1 ratio. Participants, investigators, and research personnel were masked to treatment assignment. The primary smoking end point was biochemically confirmed 4-week continuous abstinence from smoking during weeks 9 to 12, while the secondary end point was relapse to any drinking or drug use during the entire 36-week evaluation period. Logistic regression was used to determine the effects of topiramate on quitting smoking and alcohol relapse, controlling for relevant covariates. The trial is registered at ClinicalTrials.gov (number NCT00802412) and is now closed. RESULTS: Only a small proportion (7.9%) of topiramate-treated participants were able to quit smoking, and this cessation rate was similar to placebo (10.6%; odds ratio = 1.60; 95% confidence interval 0.4, 6.5; p = 0.51). Roughly 30% of the sample had a documented relapse to drinking or drug use during the study, and these rates were similar in the topiramate (20/63; 31.8%) and placebo groups (18/66; 27.3%; p = 0.58). Results of a longitudinal logistic regression model examining time to any alcohol relapse revealed no medication effect. CONCLUSIONS: Topiramate at a daily dosage of up to 200 mg per day, combined with smoking cessation and medication adherence counseling, had no effects on smoking cessation or the prevention of alcohol or drug relapse in male smokers who were in early or sustained full remission from alcohol and motivated to make a quit attempt. Alternative approaches for treating this high-risk, dually dependent population are needed.

Neural predictors of alcohol use and psychopathology symptoms in adolescents.

Adolescence is a period marked by increases in risk taking, sensation seeking, and emotion dysregulation. Neurobiological models of adolescent development propose that lagging development in brain regions associated with affect and behavior control compared to regions associated with reward and emotion processing may underlie these behavioral manifestations. Cross-sectional studies have identified several functional brain networks that may contribute to risk for substance use and psychopathology in adolescents. Determining brain structure measures that prospectively predict substance use and psychopathology could refine our understanding of the mechanisms that contribute to these problems, and lead to improved prevention efforts. Participants (N = 265) were healthy substance-naïve adolescents (ages 12-14) who underwent magnetic resonance imaging and then were followed annually for up to 13 years. Cortical thickness and surface area measures for three prefrontal regions (dorsolateral prefrontal cortex, inferior frontal gyrus, and orbitofrontal cortex) and three cortical regions from identified functional networks (anterior cingulate cortex, insular cortex, and parietal cortex) were used to predict subsequent binge drinking, externalizing symptoms, and internalizing symptoms. Thinner dorsolateral prefrontal cortex and inferior frontal cortex in early adolescence predicted more binge drinking and externalizing symptoms, respectively, in late adolescence (ps < .05). Having a family history of alcohol use disorder predicted more subsequent binge drinking and externalizing symptoms. Thinner parietal cortex, but not family history, predicted more subsequent internalizing symptoms (p < .05). This study emphasizes the temporal association between maturation of the salience, inhibition, and executive control networks in early adolescence and late adolescent behavior outcomes. Our findings indicate that developmental variations in these brain regions predate behavioral outcomes of substance use and psychopathology, and may therefore serve as prospective biomarkers of vulnerability.

Social network moderators of naltrexone and behavioral treatment effects on heavy drinking in the COMBINE study.

BACKGROUND: Oral naltrexone is an efficacious medication for treatment of alcohol dependence, but small effect sizes and variability in outcomes suggest the presence of person-level moderators of naltrexone response. Identification of contextual or psychosocial moderators may assist in guiding clinical recommendations. Given the established importance of social networks in drinking outcomes, as well as the potential effects of naltrexone in reducing cue reactivity which may be especially important among those with more heavy drinkers and more alcohol cues in their networks, we examined pretreatment social network variables as potential moderators of naltrexone treatment effects in the COMBINE study. METHODS: The sample included all COMBINE study participants in medication conditions with full data on the Important People Inventory (IPI) and covariates at intake (N = 1,197). The intake IPI assessed whether participants had any frequent drinkers in their network and the average frequency of contact with these drinkers. The effects of treatment condition, pretreatment network variables, and their interactions on percent heavy drinking days were tested in hierarchical linear models, controlling for demographics and baseline clinical covariates. RESULTS: In treatment conditions involving medical management and combined behavioral intervention (CBI), the effects of active naltrexone on heavy drinking were significantly greater for individuals with frequent drinkers in their network (z = -2.66, p < 0.01) and greater frequency of contact with those drinkers (z = -3.19, p < 0.01). These network variables did not moderate the effects of active naltrexone without CBI. CONCLUSIONS: When delivered in conjunction with behavioral interventions, naltrexone can be more potent for alcohol-dependent adults who have greater contact with frequent drinkers prior to treatment, which may indicate patterns of environmental exposure to alcohol. Contextual, social risk factors are a potential avenue to guide personalized treatment of alcohol dependence.

Up in smoke? A preliminary open-label trial of nicotine replacement therapy and cognitive behavioral motivational enhancement for smoking cessation among youth in Los Angeles.

In 2008-2009, we conducted a 6-week, open-label trial of transdermal nicotine replacement therapy and practical counseling for 34 adolescents seeking smoking cessation in Los Angeles. Dependent outcomes were study retention, use of the patch, and 7-day quit status at the end-of-study and at follow-up visits. Predictors of outcomes included cigarette dependence, withdrawal symptoms, demographic and psychiatric measures, and other substance use. Variables significant in bivariate analysis (p < .10) were retained in a multivariate model. Subjects had significant pre-to-post reductions in quit rates, dependence, and withdrawal symptoms. Subjects also reported a high number of comorbidities. Implications for clinicians are discussed.

12-step affiliation and attendance following treatment for comorbid substance dependence and depression: a latent growth curve mediation model.

Among substance-dependent individuals, comorbid major depressive disorder (MDD) is associated with greater severity and poorer treatment outcomes, but little research has examined mediators of posttreatment substance use outcomes within this population. Using latent growth curve models, the authors tested relationships between individual rates of change in 12-step involvement and substance use, utilizing posttreatment follow-up data from a trial of group Twelve-Step Facilitation (TSF) and integrated cognitive-behavioral therapy (ICBT) for veterans with substance dependence and MDD. Although TSF patients were higher on 12-step affiliation and meeting attendance at end-of-treatment as compared with ICBT, they also experienced significantly greater reductions in these variables during the year following treatment, ending at similar levels as ICBT. Veterans in TSF also had significantly greater increases in drinking frequency during follow-up, and this group difference was mediated by their greater reductions in 12-step affiliation and meeting attendance. Patients with comorbid depression appear to have difficulty sustaining high levels of 12-step involvement after the conclusion of formal 12-step interventions, which predicts poorer drinking outcomes over time. Modifications to TSF and other formal 12-step protocols or continued therapeutic contact may be necessary to sustain 12-step involvement and reduced drinking for patients with substance dependence and MDD.

Detailed Mechanisms Underlying Neutrophil Bactericidal Activity against Streptococcus pneumoniae.

Neutrophils are an essential cellular component of innate immunity and control bacterial infections through a combination of intracellular and extracellular killing methods. Although the importance of neutrophils has been established, the exact methods used to handle particular bacterial challenges and the efficiency of bacterial killing remain not well understood. In this study, we addressed how neutrophils eliminate Streptococcus pneumoniae (Spn), a leading cause of community acquired and post-influenza bacterial pneumonia. We analyzed killing methods with variable bacterial:neutrophil concentrations and following priming with PAM3CSK4 (P3CSK), an agonist for Toll-like-receptor 2 (TLR2). Our results show that murine neutrophils display surprisingly weak bactericidal activity against Spn, employing a predominantly extracellular mode of killing at lower concentrations of bacteria, whereas challenges with higher bacterial numbers induce both extracellular and intracellular elimination modes but require TLR2 activation. TLR2 activation increased reactive oxygen species (ROS) and neutrophil extracellular trap (NET) formation in response to Spn. Despite this, supernatants from P3CSK-stimulated neutrophils failed to independently alter bacterial replication. Our study reveals that unstimulated neutrophils are capable of eliminating bacteria only at lower concentrations via extracellular killing methods, whereas TLR2 activation primes neutrophil-mediated killing using both intracellular and extracellular methods under higher bacterial burdens.

The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis.

INTRODUCTION: Ketamine intravenous therapy (KIT) appears effective for treating depression in controlled trials testing a short series of infusions. A rapidly proliferating number of clinics offer KIT for depression and anxiety, using protocols without a strong evidence basis. Controlled comparison of mood and anxiety from real-world KIT clinics, and the stability of outcomes, is lacking. METHODS: We performed a retrospective controlled analysis on patients treated with KIT in ten community clinics across the US, between 08/2017-03/2020. Depression and anxiety symptoms were evaluated using the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS) and the Generalized Anxiety Disorder 7-item (GAD-7) scales, respectively. Comparison data sets from patients who did not undergo KIT were obtained from previously published real-world studies. RESULTS: Of 2758 patients treated, 714 and 836 met criteria for analysis of KIT induction and maintenance outcomes, respectively. Patients exhibited significant and concordant reduction in both anxiety and depression symptoms after induction (Cohen's d = -1.17 and d = -1.56, respectively). Compared to two external datasets of KIT-naive depressed patients or patients starting standard antidepressant therapy, KIT patients experienced a significantly greater reduction in depression symptoms at eight weeks (Cohen's d = -1.03 and d = -0.62 respectively). Furthermore, we identified a subpopulation of late-responders. During maintenance, up to a year post-induction, increases in symptoms were minimal. LIMITATIONS: Due to the retrospective nature of the analyses, interpreting this dataset is limited by incomplete patient information and sample attrition. CONCLUSIONS: KIT treatment elicited robust symptomatic relief that remained stable up to one year of follow-up.

Neutrophils drive pulmonary vascular leakage in MHV-1 infection of susceptible A/J mice.

Background: Lung inflammation, neutrophil infiltration, and pulmonary vascular leakage are pathological hallmarks of acute respiratory distress syndrome (ARDS) which can lethally complicate respiratory viral infections. Despite similar comorbidities, however, infections in some patients may be asymptomatic while others develop ARDS as seen with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections for example. Methods: In this study, we infected resistant C57BL/6 and susceptible A/J strains of mice with pulmonary administration of murine hepatitis virus strain 1 (MHV-1) to determine mechanisms underlying susceptibility to pulmonary vascular leakage in a respiratory coronavirus infection model. Results: A/J animals displayed increased lung injury parameters, pulmonary neutrophil influx, and deficient recruitment of other leukocytes early in the infection. Moreover, under basal conditions, A/J neutrophils overexpressed primary granule protein genes for myeloperoxidase and multiple serine proteases. During infection, myeloperoxidase and elastase protein were released in the bronchoalveolar spaces at higher concentrations compared to C57BL/6 mice. In contrast, genes from other granule types were not differentially expressed between these 2 strains. We found that depletion of neutrophils led to mitigation of lung injury in infected A/J mice while having no effect in the C57BL/6 mice, demonstrating that an altered neutrophil phenotype and recruitment profile is a major driver of lung immunopathology in susceptible mice. Conclusions: These results suggest that host susceptibility to pulmonary coronaviral infections may be governed in part by underlying differences in neutrophil phenotypes, which can vary between mice strains, through mechanisms involving primary granule proteins as mediators of neutrophil-driven lung injury.

Examining attendance patterns across integrated therapies for posttraumatic stress disorder and alcohol use disorder.

A substantial body of evidence supports the use of integrated treatments for posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD). Integrated trauma-focused exposure therapies reduce PTSD symptoms more than comparison treatments, including integrated coping skills therapies, but demonstrate lower attendance, raising questions regarding the relationships between attendance, outcomes, and treatment type. We aimed to examine these relationships in a RCT comparing integrated prolonged exposure (Concurrent Treatment for PTSD and Substance Use Disorders Using Prolonged Exposure, COPE; n = 58), to integrated coping skills therapy (Seeking Safety, SS; n = 52) offered in 12 sessions, with an option to extend up to four additional sessions. Participants were categorized based on number of sessions attended (0-4; 5-8; 9-12; 13-16). Multilevel modeling revealed that only when examining therapy attendance segments individually, clinical outcomes were comparable across treatments except in the 9-12 group, with COPE resulting in greater reductions in PTSD symptoms (p < 0.001), but not in alcohol use. Extending past 12 sessions was not associated with additional clinically meaningful symptom improvement for either treatment. These results suggest that attending a complete or near complete course of exposure therapy may enhance PTSD outcomes relative to non-trauma-focused therapies.

Mediating influences of negative affect and risk perception on the relationship between sensation seeking and adolescent cigarette smoking.

INTRODUCTION: A substantial number of adolescents are current and regular cigarette smokers, and there is a need to better understand factors that contribute to smoking behavior during these years. Sensation seeking (SS) is one factor that has consistently been associated with smoking, but less is known about mechanisms that may explain this relationship. METHODS: The present study tested the hypothesis that high school students high in SS would report heavier cigarette smoking and that this relationship would be mediated by negative affect and by perceptions about the risks of smoking. Students (n = 1,688) participated in an annual survey of substance use and related attitudes and characteristics. RESULTS: As expected, higher SS was associated with greater levels of past 30-day (odds ratio [OR] = 1.46, p = .004) and lifetime (OR = 1.37, p = .004) smoking, particularly for males. Multiple mediation models indicated that effect of SS on both 30-day (combined indirect effect z = 5.38, p < .001) and lifetime (z = 6.14, p < .001) smoking was mediated by both negative affect and risk perception. CONCLUSIONS: These findings suggest a need for increasing the sensation value of anti-tobacco messages to increase their efficacy for high SS youth. High SS youth may also benefit from prevention efforts designed to teach healthy ways of coping with negative affect.

Bidirectional relationship of posttraumatic stress disorder (PTSD) symptom severity and alcohol use over the course of integrated treatment.

Posttraumatic stress disorder (PTSD) and alcohol use disorder commonly co-occur. Little is known about how symptoms of one affect subsequent week symptoms of the other during the course of integrated treatment for both disorders. The sample included 107 veterans who were randomized to receive either Concurrent Treatment of PTSD and Substance Use Disorder Using Prolonged Exposure (COPE; an exposure-based trauma focused treatment) or Seeking Safety (SS; a present-focused coping skills-based treatment) and completed measures of PTSD and alcohol use at every other session. Multilevel models estimated the prospective associations between PTSD and alcohol use during treatment. Results indicated that greater PTSD symptom severity was associated with greater future alcohol use (b = 0.20, p = .024), and greater alcohol use was associated with greater future PTSD symptom severity (b = 0.13, p = .003). The effect size for PTSD symptoms to future alcohol use was larger than the reciprocal relationship. When using lagged PTSD severity to predict future drinking, results revealed that clinically significant differences in PTSD severity levels were associated with comparably large differences in drinking. Treatment condition did not moderate the effect of PTSD symptom severity on alcohol use (or the reciprocal relationship). Findings lend support to the mutual maintenance model of addiction. Integrated treatments that treat both PTSD and alcohol use may be preferential to sequential model of care where individuals are expected to achieve abstinence or reduced use prior to receiving trauma-focused treatment. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Effects of craving on opioid use are attenuated after pain coping counseling in adults with chronic pain and prescription opioid addiction.

OBJECTIVE: Risk for prescription opioid addiction is an endemic public health concern, especially for adults with chronic pain. This study examined craving as a mediator from pain to opioid use outcomes during prescription opioid addiction treatment and tested whether counseling in pain coping skills moderated the effects of craving on treatment outcomes. METHOD: Secondary analysis on a sample (N = 148) randomized to standard or enhanced counseling for 12 weeks with adjunct opioid maintenance medication. Multilevel analyses examined mediated effects between weekly pain, craving, and opioid use, and tested the interaction between craving and a counseling module on pain coping skills. RESULTS: Greater pain predicted greater craving (ß = 0.25, p < .001), which predicted next-week opioid use (ß = 0.17, p < .001). A statistically significant indirect effect of craving (ß = 0.04, 95% CI [0.02, 0.06]) mediated 95% of the total effect from pain to opioid use. A significant interaction (b = -0.22, p < .01) revealed that after receiving the pain coping module, the association between craving and next-week opioid use was reduced, with greater exposure to the module associated with stronger effects (b = -0.12, p < .01). CONCLUSION: More severe pain predicts greater opioid use due to the association between pain and cravings. Pain coping skills counseling suppressed the association between cravings and opioid use. For adults with chronic pain receiving treatment for prescription opioid addiction, interventions that address cravings through behavioral pain coping skills may be crucial for achieving optimal treatment outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Short Communication: Effect of Seminal Plasma on Functions of Monocytes and Granulocytes.

Most HIV-1 transmissions occur at mucosae and involve exposure to semen. Semen contains immunomodulatory factors, which inhibit anti-HIV-1 natural killer cell and T cell responses. We demonstrate high concentrations (1:2 dilution) of seminal plasma (SP) inhibit monocyte phagocytosis and anti-HIV-1 Fc-dependent functions of both neutrophils and monocytes. In addition, slightly lower SP concentrations (1:2-1:10 dilutions) inhibit granulocyte phagocytosis and oxidative burst of both monocytes and granulocytes. These observations may have implications for HIV-1 infectivity after mucosal exposure.

Additional treatment services in a cocaine treatment study: level of services obtained and impact on outcome.

The objective of this study was to examine the level of additional treatment services obtained by patients enrolled in the NIDA Cocaine Collaborative Study, a multi-center efficacy trial of four treatments for cocaine dependence, and to determine whether these services impact treatment outcome. Cocaine-dependent patients (N = 487) were recruited at five sites and randomly assigned to six months of one of four psychosocial treatments. Assessments were made at baseline, monthly during treatment, and at follow-ups at 9, 12, 15, and 18 months post-randomization. On average, patients received little or no additional treatment services during active treatment (first six months), but the rate of obtaining most services increased during the follow-up phase (month 7 to 18). In general, the treatment groups did not differ in the rates of obtaining non-protocol services. For all treatment groups, patients with greater psychiatric severity received more medical and psychiatric services during active treatment and follow-up. Use of treatment services was unrelated to drug use outcomes during active treatment. However, during the follow-up period, increased use of psychiatric medication, twelve-step attendance, and twelve-step participation was related to less drug use. The results suggest that during uncontrolled follow-up phases, additional non-protocol services may potentially confound the interpretation of treatment group comparisons in drug use outcomes.

Supportive-Expressive Psychodynamic Therapy for Cocaine Dependence: A Closer Look.

Using data from the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, this article focuses on the outcomes of patients who received supportive-expressive (SE) psychodynamically-oriented psychotherapy (plus group drug counseling; GDC). Short-term SE for cocaine dependent individuals, while not the most efficacious treatment examined in the study (individual drug counseling [IDC] plus GDC was), produced large improvements in cocaine use. In addition, there was evidence that SE was superior to IDC on change in family/social problems at the 12 month follow-up assessment, particularly for those patients with relatively more severe difficulties in this domain at baseline. For patients who achieved abstinence early in treatment, SE produced comparable drug use outcomes to IDC, with mean drug use scores numerically lower for SE at all of the follow-up assessments (9, 12, 15, and 18 months). SE patients who achieved initial abstinence decreased cocaine use from a mean 10.1 days per month at baseline to a mean of 1.3 days at 12 months.

Improvement in Negative Symptoms and Functioning in Cognitive-Behavioral Social Skills Training for Schizophrenia: Mediation by Defeatist Performance Attitudes and Asocial Beliefs.

Psychosocial interventions have significant but modest impact on negative symptoms and functioning in schizophrenia. Identifying mechanisms of change in these interventions can inform treatment targets to strengthen these interventions. A number of studies have found associations between dysfunctional attitudes negative symptoms and functioning in schizophrenia. We previously found improvement in experiential negative symptoms and functioning in cognitive-behavioral social skills training (CBSST) in participants with schizophrenia (N = 149), and the present study examined whether improvements in CBSST in that trial were mediated by the group effect on defeatist performance attitudes and asocial beliefs. In multilevel mediation analyses, the effect of treatment group on experiential negative symptoms and functioning was mediated prospectively through defeatist attitudes but asocial beliefs only mediated effects on experiential negative symptoms. The findings suggest that cognitive-behavioral therapy interventions that target dysfunctional attitudes can lead to improvement in negative symptoms and functioning in schizophrenia.

The effects of alcohol hangover on future drinking behavior and the development of alcohol problems.

INTRODUCTION: Alcohol hangover experiences in young adulthood have been shown to predict more subsequent alcohol problems. Hangover susceptibility appears to be partially heritable and related to family history of alcohol use disorders. However, very little is known about the developmental course of these associations and whether they are accounted for by an individual's drinking history. The goal of this study is to investigate the prospective and unique relationships between family history of alcohol use disorders, severity of alcohol hangover experiences in adolescence, and later alcohol use and related problems measured over 13years. METHODS: Participants were first assessed on family history at age 12-14, prior to initiating drinking, and re-assessed annually on hangover severity, drinks per drinking day (DPDD), and alcohol-related problems throughout the 13-year follow-up period (n=205; 59% male). RESULTS: In mixed effects negative binomial regression models, greater family history density scores predicted more future DPDD (Incidence Rate Ratio [IRR]=1.19, p=0.04), alcohol problems (IRR=1.64, p=0.05), and future hangover severity (IRR=1.24; p=0.01). In turn, greater hangover severity predicted more future DPDD (IRR=1.03; p=0.002) and alcohol problems (IRR=1.12, p<0.001), and hangover severity mediated the relationship between family history and alcohol use/problems. All models controlled for participant age, sex, and past drinking behavior (where relevant). CONCLUSIONS: These results advance the alcohol hangover experience during late adolescence as a clinically relevant and uniquely informative marker of future alcohol use and problems, above and beyond that of prior personal or familial drinking history.

Predictors of reduced smoking quantity among recovering alcohol dependent men in a smoking cessation trial.

INTRODUCTION: Adults with alcohol dependence (AD) have exceptionally high smoking rates and poor smoking cessation outcomes. Discovery of factors that predict reduced smoking among AD smokers may help improve treatment. This study examined baseline predictors of smoking quantity among AD smokers in a pharmacotherapy trial for smoking cessation. METHODS: The sample includes male, AD smokers (N = 129) with 1-32 months of alcohol abstinence who participated in a 12-week trial of medication (topiramate vs. placebo) and adjunct counseling with 6 months of follow-up. Baseline measures of nicotine dependence, AD severity, psychopathology, motivation to quit smoking, and smoking-related cognitions were used to predict smoking quantity (cigarettes per day) at post-treatment and follow-up. RESULTS: Overall, the sample had statistically significant reductions in smoking quantity. Greater nicotine dependence (Incidence rate ratios (IRRs) = 0.82-0.90), motivation to quit (IRRs = 0.65-0.85), and intrinsic reasons for quitting (IRRs = 0.96-0.98) predicted fewer cigarettes/day. Conversely, greater lifetime AD severity (IRR = 1.02), depression severity (IRRs = 1.05-1.07), impulsivity (IRRs = 1.01-1.03), weight-control expectancies (IRRs = 1.10-1.15), and childhood sexual abuse (IRRs = 1.03-1.07) predicted more cigarettes/day. CONCLUSIONS: Smokers with AD can achieve large reductions in smoking quantity during treatment, and factors that predict smoking outcomes in the general population also predict greater smoking reductions in AD smokers. Treatment providers can use severity of nicotine dependence and AD, motivation to quit, smoking-related cognitions, and severity of depression to guide treatment and improve outcomes among AD smokers.