The Serotonin Transporter Polymorphism (5-HTTLPR) and Alcohol Problems in Heavy Drinkers: Moderation by Depressive Symptoms.

Heavy alcohol use in young adults has been prospectively associated with a host of psychosocial and alcohol-related problems. Recent studies have supported the interaction between serotonin transporter polymorphism and adverse environmental factors, as a predictor of alcohol use and the development of alcohol dependence. The current study examined the role of depressive symptoms in combination with the serotonin transporter polymorphism as a predictor of alcohol use and alcohol-related problems. Results revealed a significant genotype by depressive symptom interaction, such that heavier alcohol use was associated with depressive symptoms in L allele homozygotes but not among S allele carriers. These results remained significant after controlling for ethnicity and gender effects. These findings extend the emerging literature supporting 5-HTTLPR genotype as a risk factor for alcohol-related problems in the context of co-occurring symptoms of depression

Relationship between tonic and phasic craving for alcohol.

BackgroundMultiple measures are utilized to assess alcohol craving, often interchangeably. Little is known about the relationship between tonic and phasic craving. This study fills this gap in the literature by examining the association between tonic levels of alcohol craving and phasic craving for alcohol that is provoked by alcohol administration.MethodsForty-three non-treatment seeking problem drinkers underwent an initial interview and two laboratory testing sessions, where either alcohol or a saline placebo was administered intravenously. Tonic craving was assessed via the Penn Alcohol Craving Scale (PACS) and Obsessive Compulsive Drinking Scale (OCDS) at the initial interview. Phasic craving was assessed during the laboratory sessions (i.e., alcohol and saline administrations, single blinded) at baseline and at 3 subsequent breath alcohol concentrations (0.02, 0.04, and 0.06 g/dl).ResultsThere was a main effect of PACS in predicting phasic craving across both saline and alcohol administration conditions (p < 0.05). The OCDS was predictive of phasic craving when alcohol, but not saline, was administered (p = 0.058); the obsessive subscale (p = 0.01), but not the compulsive subscale (p > 0.10), predicted phasic craving during alcohol, as compared to saline administration.ConclusionIn sum, tonic craving captured by the OCDS was predictive of phasic craving during alcohol administration whereas the PACS more generally captured the increase in phasic craving. Therefore, these measures of tonic craving may function differently in capturing the experience of phasic craving. Implications for the utilization of the PACS and OCDS as well as assessments of craving in alcoholism research are discussed

Convergence between the Penn Alcohol Craving Scale and diagnostic interview for the assessment of alcohol craving.

IntroductionThe Penn Alcohol Craving Scale (PACS) is one of the most widely used instruments to measure craving for alcohol. Recent research has suggested that scores on the PACS can be used as a "stand in" for the diagnostic criterion of alcohol craving with a proposed cutoff of >20 on the PACS indicating a "positive" alcohol craving symptom. The present study examined the convergence between the PACS and face-to-face diagnostic interview for the assessment of alcohol craving.MethodA sample of non-treatment seeking heavy drinkers (N = 338) enrolled in experimental studies of AUD completed the PACS as well as a face-to-face diagnostic interview for AUD, which included the craving item from the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA).ResultsUsing the PACS cut-off score of >20, 12.9% (N = 43) of the sample met criteria for alcohol craving compared to 21% (N = 74) of the sample meeting criteria based on the diagnostic interview. Using the PACS cutoff of >20, sensitivity (i.e., true positive rate) was 41% and specificity (i.e., true negative rate) was 95%. Exploratory analyses suggested that a cut-off score of ≥15 achieved the optimal balance of sensitivity (67%) and specificity (81%) in our sample.ConclusionsAdvancing the assessment of alcohol craving and the conversion from DSM-IV to DSM-5 diagnostic criteria represents an important research direction. The present study recommends that a PACS score cut off of ≥15 should be used as an indicator of clinically significant alcohol craving in community samples of non-treatment seekers

Examining the moderating role of cannabis use on the relationship between alcohol consumption and inflammation in individuals with alcohol use disorder.

Inflammation appears to be a critical mechanism in the development of alcohol use disorder (AUD) and a consequence of chronic alcohol use. The potential anti-inflammatory properties of cannabis may modulate the proinflammatory effects of alcohol. This study sought to extend previous work investigating the relationship between alcohol consumption, cannabis use and circulating interleukin (IL)-6 levels in a sample with AUD. One hundred and thirty-three individuals with an AUD provided blood samples to assess IL-6 and answered questions regarding alcohol and cannabis use. An ordinary least squares multiple regression analysis was conducted to assess the effect of alcohol and cannabis use on IL-6. A moderation analysis examined cannabis use as a potential moderator of the relationship between alcohol use and circulating IL-6 levels. Alcohol use was predictive of higher log IL-6 levels (standardized β = 0.16, p = 0.03), while cannabis use was not predictive of log IL-6 levels (p = 0.36). Days of cannabis use moderated the relationship between alcohol use and IL-6 levels, such that the relationship between alcohol use and IL-6 levels was only significant in individuals with AUD without recent cannabis use. This study extends previous work to a clinical sample with an AUD and underscores the importance of considering cannabis use in studies on alcohol use and inflammation. This study also indicates the need for in-depth analyses on cannabinoids and inflammation and the interaction between cannabinoids and alcohol use on inflammation

An Examination of Motivation to Change and Neural Alcohol Cue Reactivity Following a Brief Intervention.

Background: Brief interventions represent a promising psychological intervention targeting individuals with heavy alcohol use. Motivation to change represents an individual's openness to engage in a behavior change strategy and is thought to be a crucial component of brief interventions. Neuroimaging techniques provide a translational tool to investigate the neurobiological mechanisms underlying potential mediators of treatment response, including motivation to change. Therefore, this study aimed to examine the effect of a brief intervention on motivation to change drinking behavior and neural alcohol taste cue reactivity. Methods: Non-treatment-seeking heavy drinkers were randomized to receive a brief drinking intervention (n = 22) or an attention-matched control (n = 24). Three indices of motivation to change were assessed at baseline and after the intervention or control session: importance, confidence, and readiness. Immediately following the intervention or control session, participants also underwent an functional magnetic resonance imaging (fMRI) during which they completed an alcohol taste cues paradigm. Results: There was a significant effect of the brief intervention on increasing ratings of importance of changing drinking behavior, but not on ratings of confidence or readiness to change. Ratings of importance after the intervention or control session were associated with neural alcohol taste cue reactivity, but notably, this effect was only significant for participants who received the intervention. Individuals in the intervention condition showed a positive association between ratings of importance and activation in the precuneus, posterior cingulate, and insula. Conclusions: The brief drinking intervention was successful at improving one dimension of motivation to change among non-treatment-seeking heavy drinkers. The brief intervention moderated the relationship between ratings of importance and brain activation in circuitry associated with interoceptive awareness and self-reflection. Together, findings represent an initial step toward understanding the neurobiological mechanisms through which a brief intervention may improve motivation to change

The Effect of Olanzapine on Craving and Alcohol Consumption

Previous studies have indicated that olanzapine decreases craving after a priming dose of alcohol, that craving after a priming dose of alcohol is greater among individuals with the seven-repeat allele of the DRD4 variable number of tandem repeats (VNTR) polymorphism, and that the effect of olanzapine (a D2/D4 antagonist) is more pronounced among individuals with this allele. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving and differentially effective as a treatment for alcohol dependence over the course of a 12-week, randomized, placebo-controlled trial among individuals with and without the seven-repeat allele. Participants who met DSM IV criteria for alcohol dependence were randomly assigned to receive olanzapine (5 mg) or a placebo over the course of the trial. After 2 weeks of treatment, participants completed a cue reactivity assessment. The results suggested that participants who were homozygous or heterozygous for the seven (or longer)-repeat allele of the DRD4 VNTR responded to olanzapine with reductions in cue-elicited craving as well as reductions in alcohol consumption over the course of the 12-week trial, whereas individuals with the shorter alleles did not respond favorably to olanzapine

Endpoints for Pharmacotherapy Trials for Alcohol Use Disorder.

Alcohol use disorder (AUD) is a debilitating disorder, yet currently approved pharmacotherapies to treat AUD are under-utilized. The three medications approved by the US Food and Drug Administration (FDA) for the indication of AUD are disulfiram, acamprosate, and naltrexone. The current landscape of pharmacotherapies for AUD suggests opportunities for improvement. Clinical trials investigating novel pharmacotherapies for AUD traditionally use abstinence-based drinking outcomes or no heavy drinking days as trial endpoints to determine the efficacy of pharmacotherapies. These outcomes are typically measured through patient self-report endorsements of their drinking. Apart from these traditional outcomes, there have been recent developments in novel endpoints for AUD pharmacotherapies. These novel endpoints include utilizing the World Health Organization (WHO) risk drinking level reductions to promote a harm-reduction endpoint rather than an abstinence-based endpoint. Additionally, in contrast to patient self-report measurements, biological markers of alcohol use may serve as objective endpoints in AUD pharmacotherapy trials. Lastly, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) definition of recovery from AUD and patient-oriented outcomes offer new frameworks to consider endpoints associated with more than alcohol consumption itself, such as the provider-patient experiences with novel pharmacotherapies. These recent developments in new endpoints for AUD pharmacotherapies offer promising future opportunities for pharmacotherapy development, so long as validity and reliability measures are demonstrated for the endpoints. A greater breadth of endpoint utilization may better capture the complexity of AUD symptomatology

The Effects of Naltrexone Among Alcohol Non-Abstainers: Results from the COMBINE Study

These analyses of the COMBINE Study examined the effects of naltrexone among non-abstainers. Given that one of the most well-established mechanisms of action of naltrexone involves blunting of alcohol reward, it is hypothesized that naltrexone should be more effective among individuals who drank during treatment. Participants were 952 (78% of the total COMBINE Study sample) treatment-seeking alcohol-dependent men and women who received pharmacotherapy for alcoholism and drank at least once during the 16-week trial. Mixed model analyses revealed that individuals who drank more regularly during the trial seemed to benefit most from naltrexone and the effects of naltrexone on heavy drinking was significant in treatment months 2 through 4 among individuals who reported drinking on 81, 68, and 60% or more of days, respectively. Those drinking frequencies were observed in 11, 15, and 19% of the sample. Similar effects were not observed for drinks per drinking day. These results suggest that a small subgroup of non-abstainers, composed primarily of very regular drinkers, appears to benefit from naltrexone in reducing heavy drinking days. Naltrexone may be effective in the context of controlled-drinking approaches, even among very frequent drinkers

Friction stir welding of HT9 ferritic-martensitic steel: an assessment of microstructure and properties

This thesis explores the processing-microstructure-property relationships in friction stir welded (FSW) HT9A ferritic-martensitic steel. HT9 has previously been studied as a structural component for fusion/fission based reactors; however, the changes in material microstructure and properties after friction stir welding have not been considered. HT9A steel plate was friction stir welded with a series of increasing heat inputs. The microstructure of this welded material was characterized using optical and electron microscopy. The mechanical properties of the welded material were determined using nanoindentation and microhardness measurements. In addition, electrochemical impedance spectroscopy (EIS) in molten lithium fluoride was used to assess the high temperature corrosion resistance of the welded material in the harsh environments found in fusion reactors. The quality of the friction stir welds was excellent, and the basic ferritic-martensitic microstructure was maintained for all of the conditions used. Some reduction in hardness was observed in the welded material, particularly in the heat affected zones. The high temperature corrosion response of the welded material was comparable to, or slightly better than, the base plate material.http://archive.org/details/frictionstirweld1094534726Outstanding ThesisLieutenant, United States NavyApproved for public release; distribution is unlimited