Showing papers in "Alcoholism: Clinical and Experimental Research in 2007"

AUDIT-C as a Brief Screen for Alcohol Misuse in Primary Care

Abstract: Background: The Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questions have been previously validated as a 3-item screen for alcohol misuse and implemented nationwide in Veterans Affairs (VA) outpatient clinics. However, the AUDIT-C's validity and optimal screening threshold(s) in other clinical populations are unknown. Methods: This cross-sectional validation study compared screening questionnaires with standardized interviews in 392 male and 927 female adult outpatients at an academic family practice clinic from 1993 to 1994. The AUDIT-C, full AUDIT, self-reported risky drinking, AUDIT question #3, and an augmented CAGE questionnaire were compared with an interview primary reference standard of alcohol misuse, defined as a Diagnostic and Statistical Manual, 4th ed. alcohol use disorder and/or drinking above recommended limits in the past year. Results: Based on interviews with 92% of eligible patients, 128 (33%) men and 177 (19%) women met the criteria for alcohol misuse. Areas under the receiver operating characteristic curves (AUROCs) for the AUDIT-C were 0.94 (0.91, 0.96) and 0.90 (0.87, 0.93) in men and women, respectively (p=0.04). Based on AUROC curves, the AUDIT-C performed as well as the full AUDIT and significantly better than self-reported risky drinking, AUDIT question #3, or the augmented CAGE questionnaire (p-values <0.001). The AUDIT-C screening thresholds that simultaneously maximized sensitivity and specificity were ≥4 in men (sensitivity 0.86, specificity 0.89) and ≥3 in women (sensitivity 0.73, specificity 0.91). Conclusions: The AUDIT-C was an effective screening test for alcohol misuse in this primary care sample. Optimal screening thresholds for alcohol misuse among men (≥4) and women (≥3) were the same as in previously published VA studies.

The Alcohol Use Disorders Identification Test: An Update of Research Findings

Abstract: Background: The Alcohol Use Disorders Identification Test (AUDIT) has been extensively researched to determine its capability to accurately and practically screen for alcohol problems. Methods: During the 5 years since our previous review of the literature, a large number of additional studies have been published on the AUDIT, abbreviated versions of it, its psychometric properties, and the applicability of the AUDIT for a diverse array of populations. The current article summarizes new findings and integrates them with results of previous research. It also suggests some issues that we believe are particularly in need of further study. Results: A growing body of research evidence supports the criterion validity of English version of the AUDIT as a screen for alcohol dependence as well as for less severe alcohol problems. Nevertheless, the cut-points for effective detection of hazardous drinking as well as identification of alcohol dependence or harmful use in women need to be lowered from the originally recommended value of 8 points. The AUDIT-C, the most popular short version of the AUDIT consisting solely of its 3 consumption items, is approximately equal in accuracy to the full AUDIT. Psychometric properties of the AUDIT, such as test–retest reliability and internal consistency, are quite favorable. Continued research is urged to establish the psychometric properties of non-English versions of the AUDIT, use of the AUDIT with adolescents and with older adults, and selective inclusion of alcohol biomarkers with the AUDIT in some instances. Conclusions: Research continues to support use of the AUDIT as a means of screening for the spectrum of alcohol use disorders in various settings and with diverse populations.

Client language as a mediator of motivational interviewing efficacy: where is the evidence?

Abstract: Background: Identifying in-session indicators of client outcomes is important in determining the mechanisms of psychotherapeutic treatments, including Motivational Interviewing (MI) The current studies sought to determine if clinician behavior influences client speech, and the extent to which client speech predicted treatment outcome in clients receiving treatment for substance abuse Methods: Study 1 examined 38 sessions from 5 sites in Project MATCH Sessions were coded using the Sequential Code for Process Exchanges (SCOPE) behavioral coding system Transition probabilities and inter-rater reliability were calculated Study 2 examined 45 sessions from the New Mexico site in Project MATCH Sessions were coded using the MISC 10 behavioral coding system Distal outcome measures were calculated for proportion of days abstinent (PDA) and drinks per drinking day (DDD) Hierarchical multiple regression and hierarchical logistic regression were used to characterize the relationship between client speech and outcome Results: In Study 1, inter-rater reliability estimates indicate that coders reliably distinguished between the categories within the SCOPE Behaviors consistent with MI (MICO) were significantly likely to be followed by client Change Talk (CT) and behaviors inconsistent with MI (MIIN) were significantly likely to be followed by Counterchange Talk (CCT) There was also a significant negative transition probability between MICO and CCT In Study 2, CT was found to account for significant portions of outcome variability beyond that attributable to baseline measures of problem severity Conclusions: Client speech during early therapy sessions appears to be a powerful predictor of substance abuse outcome The pattern of therapist behaviors and subsequent client language found in this data supports the intervention test in the causal chain we have described for motivational interviewing These studies provide preliminary support for a causal chain between therapist behaviors, subsequent client speech, and drinking outcomes within motivational interviewing sessions The results of both studies provide further support to the proposition that client speech impacts the likelihood of behavioral change, and that the occurrence of such speech is influenced by the therapist

Stress-Induced and Alcohol Cue-Induced Craving in Recently Abstinent Alcohol-Dependent Individuals

Abstract: Background: Research has shown that exposure to stress/negative affect and to alcohol cues can each increase alcohol craving and relapse susceptibility in alcohol-dependent individuals. However, whether the emotional and physiological states associated with stress-induced and alcohol cue-induced craving are comparable has not been well studied. Therefore, this study examined the craving, emotional, and physiological responses to stress and to alcohol cues in treatment-engaged, 4-week abstinent, alcohol-dependent individuals using analogous stress and alcohol cue imagery methods. Method: Twenty treatment-seeking, alcohol-dependent participants (18 males/2 females) were exposed to a brief 5-minute guided imagery procedure that involved imagining a recent personal stressful situation, a personal alcohol cue-related situation, and a neutral-relaxing situation, 1 imagery per session presented in random order. Alcohol craving, anxiety and emotion rating scales, cardiovascular measures, and salivary cortisol were compared across the 3 conditions. Results: Exposure to stress and to alcohol cues each produced significant increases in alcohol craving, anxiety, and negative emotions and decreases in positive emotions. Stress-induced alcohol craving was significantly correlated with increases in sadness, anger, and anxiety ratings, but alcohol cue-induced craving was associated with decreases in positive affect (joy and neutral relaxed state) and increases in anxiety and fear ratings. Furthermore, stress increased systolic and diastolic blood pressure responses, but significant increases in salivary cortisol were only observed in the alcohol cue condition. Conclusions: Although both stress and alcohol cues produce increases in anxiety associated with alcohol craving, each produced a dissociable psychobiological state involving subjective emotional, cardiovascular, and cortisol responses. These data could have significant implications for understanding the specific psychobiology associated with stress or alcohol cue exposure and their potential effects on alcohol relapse susceptibility.

Decision making and binge drinking: a longitudinal study.

Abstract: Alcohol dependent individuals perform worse than controls on tests of neurocognitive functions. For example, persons with a history of alcohol dependence display disadvantageous decision making compared with persons without substance dependence (Bechara et al., 2001). Also, diminished executive functions, that is, self-regulatory functions necessary for goal-directed behavior, have been found in persons with alcohol dependence (for a review, see Giancola and Moss, 1998). Heavy social drinkers (i.e., 21 drinks or more per week) have also been found to display mild deficits on a variety of neurocognitive functions, such as attention, memory, and visuospatial abilities (for a review, see Parsons and Nixon, 1998). Notably, recent neurobehavioral addiction theories have highlighted relations between substance dependence and neural dysfunction, particularly in the ventromedial prefrontal cortex, striatum, and basal ganglia (Goldstein and Volkow, 2002). These brain areas are important in neurocognitive functions involving the evaluation and appraisal of positive and negative consequences, functions which play a role in decision making (Krawczyk, 2002). To date, however, no studies have examined the relation between different longitudinal patterns of alcohol use and decision making or other affective neurocognitive functions. Decision-making skills may be especially important during late adolescence and young adulthood, as this is often a time of change, identity development, and educational and career development. In addition, young adulthood is often a period of heavy alcohol use. For example, a recent study reported that 23% of college students were frequent binge drinkers, and 44% engaged in binge drinking in the past 2 weeks (Wechsler et al., 2000). Some studies suggest that the adolescent brain may be particularly vulnerable to the harmful effects of alcohol. Recent studies indicate that binge drinking has a more detrimental effect on brain structure and functioning in adolescent, compared with adult rats (Crews et al., 2000; Monti et al., 2005). Notably, in humans, the pre-frontal lobes mature throughout adolescence, and into early adulthood (Casey et al., 2000). Therefore, decision-making skills, which rely on prefrontal lobe functioning, may be especially vulnerable to the effects of heavy alcohol use during adolescence. Recent research has highlighted considerable variability in drinking patterns (Cho et al., 2001; Mundt et al., 1995; Searles et al., 2000), and it is unclear whether different drinking trajectories are differentially related to neurocognitive functioning. Therefore, in this study, 200 participants were selected from a large longitudinal study, based on their drinking course over a recent 2.5-year period. Four groups of college students were included, differing in onset and amount of binge drinking. Thus, we were able to investigate what patterns of heavy (binge) drinking were related to diminished decision making. In the alcohol and drug-use literature, an abundance of studies indicate that different developmental trajectories exist for binge drinking. These studies consistently find the existence of stable-low, increasing, and stable-high subgroups (Chassin et al., 2002; Hill et al., 2000; Tucker et al., 2003), with increasing and stable-high subgroups having a higher prevalence in college student samples (Schulenberg and Maggs, 2002). When different drinking trajectories are associated with differences in decision making, this could have consequences for the way in which prevention and intervention strategies target binge drinking, such as targeting groups with a specific binge drinking trajectory (Jackson et al., 2004). Another possibility in explaining differences in decision-making abilities and drinking patterns, may be differences in age of onset of drinking. Differences in age of onset of drinking may indicate being in a more advanced phase of a progression of drinking behavior, or a more severe binge-drinking pattern. Therefore, the effect of age of onset of drinking was examined as well. Recently, controversy surrounds the definition of binge drinking, as the traditional definitions of binge drinking (5/4 drinks per occasion) may be too low for patterns of binge drinking in college students (White et al., 2006). We sampled students on the traditional measure of 5 drinks within 1 sitting, and thus, this measure of binge drinking may underestimate heavy binge drinking. However, binge drinking and a measure of quantity/frequency of alcohol use in this college student sample are highly correlated. We therefore refer to heavy (binge) drinking, or to alcohol use trajectories, and not solely to binge drinking. The current study thus examined relationships between several longitudinal patterns of heavy (binge) drinking, and decision-making skills in a sample of young adults. Decision making was studied using the Iowa Gambling Task (IGT; Bechara et al., 1999). In the IGT, participants play a computerized card game in which they attempt to develop a winning strategy by selecting cards from advantageous, as opposed to disadvantageous decks. Participants have to learn, over the course of the task, which decks are advantageous and which are disadvantageous. Disadvantageous choice patterns on the IGT have been found in a substantial number of studies of people with ventromedial prefrontal lobe damage (Bechara et al., 1994, 2001; but see Manes et al., 2002), and populations with a variety of disinhibited behaviors (Goudriaan et al., 2005; Grant et al., 2000; Rotherham-Fuller et al., 2004; van Honk et al., 2002; Whitlow et al., 2004). Other factors have also been found to affect IGT performance. In particular, attention deficit hyperactivity disorder (ADHD) is negatively related to performance on decision-making tasks (Ernst et al., 2003a, 2003b; Murphy et al., 2001; Raghunathan and Pham, 1999) and is also associated with alcohol dependence (Farrell et al., 2001; Kessler et al., 1997). Higher impulsivity has been related to both poor IGT performance (Crone et al., 2003) and heavy alcohol use (Waldeck and Miller, 1997). A secondary aim of this study therefore was to investigate the influence of both externalizing psychopathological symptoms and impulsivity, on IGT performance. We were also interested in the relation between gender and decision making. The literature on gender and IGT performance is mixed. Two studies of IGT performance have found that women perform less well than men (Bolla et al., 2004; Reavis and Overman, 2001), but other studies have not found gender differences in performance levels (Crone et al., 2003; Fein et al., 2004, 2006; Hooper et al., 2004). One of these studies did indicate a difference in frequency of punishment preference between girls and boys, with both girls and boys preferring lower frequency punishments of a higher amount, but girls having a stronger preference for this response option (Hooper et al., 2004). A brain imaging study reports that men and women also activated different orbitofrontal brain areas during IGT performance (Bolla et al., 2004). Our study consisted of a comparatively large young adult sample with equal gender distribution, and was thus especially suitable for studying the effects of gender on IGT performance and contingency preferences. In summary, the current study is the first to examine relations between decision making and longitudinal heavy (binge) drinking patterns in a large, mixed-gender sample of young adults. In addition, this study examined the degree to which externalizing psychopathology, impulsivity and gender affected the IGT/binge-drinking relation. We aimed to determine whether low-binge drinkers differed from (a) students who engaged in moderate-binge drinking, (b) students who increased their binge drinking when entering college, (c) students who engaged in high-binge drinking both before entering college, and throughout the first 2 college years. We hypothesized that consistent high levels of binge drinking and heavy alcohol use would have a detrimental effect on decision making, as measured by the IGT.

Rates and Correlates of Relapse Among Individuals in Remission From DSM-IV Alcohol Dependence: A 3-Year Follow-Up

Abstract: BACKGROUND: There is little information on the stability of abstinent and nonabstinent remission from alcohol dependence in the general U.S. population. The aim of this study was to examine longitudinal changes in recovery status among individuals in remission from DSM-IV alcohol dependence, including rates and correlates of relapse, over a 3-year period. METHODS: This analysis is based on data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of U.S. adults aged 18 years and older originally interviewed in 2001 to 2002 and reinterviewed in 2004 to 2005. The Wave 1 NESARC identified 2,109 individuals who met the DSM-IV criteria for full remission from alcohol dependence. Of these, 1,772 were reinterviewed at Wave 2, comprising the analytic sample for this study. Recovery status at Wave 2 was examined as a function of type of remission at Wave 1, with a focus on rates of relapse, alternately defined as recurrence of any alcohol use disorder (AUD) symptoms and recurrence of DSM-IV alcohol dependence. Logistic regression models were used to estimate the odds of relapse among asymptomatic risk drinkers and low-risk drinkers relative to abstainers, adjusted for a wide range of potential confounders. RESULTS: By Wave 2, 51.0% of the Wave 1 asymptomatic risk drinkers had experienced the recurrence of AUD symptoms, compared with 27.2% of low-risk drinkers and 7.3% of abstainers. Across all ages combined, the adjusted odds of recurrence of AUD symptoms relative to abstainers were 14.6 times as great for asymptomatic risk drinkers and 5.8 times as great for low-risk drinkers. The proportions of individuals who had experienced the recurrence of dependence were 10.2, 4.0, and 2.9%, respectively, and the adjusted odds ratios relative to abstainers were 7.0 for asymptomatic risk drinkers and 3.0 for low-risk drinkers. Age significantly modified the association between type of remission and relapse. Differences by type of remission were not significant for younger alcoholics, who had the highest rates of relapse. CONCLUSIONS: Abstinence represents the most stable form of remission for most recovering alcoholics. Study findings highlight the need for better approaches to maintaining recovery among young adults in remission from alcohol dependence, who are at particularly high risk of relapse. Language: en

Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study.

Abstract: Background: Pharmacotherapy of alcohol dependence (AD) is at an early stage of development; currently available medications have limited efficacy. It would be clinically valuable to identify, before initiation of a course of treatment, those patients who, based on genetic markers, are most likely to respond to a specific pharmacotherapy. A previous report suggested that a functional variant at the genetic locus encoding the μ opioid receptor (Asn40Asp) is such a marker, in short-term (3-month) treatment with the opioid-blocking drug naltrexone (NTX). Methods: We studied polymorphic variants at each of the 3 opioid receptor genes—OPRM1, OPRD1, and OPRK1, which encode the μ, δ, and κ opioid receptors, respectively—including the OPRM1 Asn40Asp variant—as predictors of response to NTX or placebo in 215 alcohol-dependent male subjects who participated in Veterans Affairs Cooperative Study 425, “Naltrexone in the Treatment of Alcohol Dependence.” Results: At the 3-month time point, treatment condition, age, and the pretreatment number of drinks per drinking day were all significant (p<0.05) predictors of the rate of relapse and time to relapse. Although NTX had no significant effect on relapse to heavy drinking in the overall sample in CSP 425, it significantly reduced relapse in the subgroup that provided DNA for analysis (i.e., the present study sample). There were no significant interactions between any individual single nucleotide polymorphisms studied and NTX treatment response. Conclusions: These results do not support association of the OPRM1 Asn40Asp polymorphism with NTX treatment response for AD.

Increased drinking during withdrawal from intermittent ethanol exposure is blocked by the CRF receptor antagonist D-Phe-CRF(12-41).

Abstract: Background: Studies in rodents have determined that intermittent exposure to alcohol vapor can increase subsequent ethanol self-administration, measured with operant and 2-bottle choice procedures. Two key procedural factors in demonstrating increased alcohol intake are the establishment of stable alcohol self-administration before alcohol vapor exposure and the number of bouts of intermittent vapor exposure. The present studies provide additional behavioral validation and initial pharmacological validation of this withdrawal-associated drinking procedure. Methods: Studies at 2 different sites (Portland and Scripps) examined the effect of intermittent ethanol vapor exposure (3 cycles of 16 hours of ethanol vapor+8 hours air) on 2-hour limited access ethanol preference drinking in male C57BL/6 mice. Separate studies tested 10 or 15% (v/v) ethanol concentrations, and measured intake during the circadian dark. In one study, before measuring ethanol intake after the second bout of intermittent vapor exposure, mice were tested for handling-induced convulsions (HICs) indicative of physical dependence on ethanol. In a second study, the effect of bilateral infusions of the corticotropin-releasing factor (CRF) receptor antagonist d-Phe-CRF(12–41) (0.25 μg/0.5 μL) into the central nucleus of the amygdala (CeA) on ethanol intake was compared in vapor-exposed animals and air controls. Results: Intermittent ethanol vapor exposure significantly increased ethanol intake by 30 to 40%, and the mice had higher blood ethanol concentrations than controls. Intra-amygdala infusions of d-Phe-CRF(12–41) significantly decreased the withdrawal-associated increase in ethanol intake without altering ethanol consumption in controls. Following the second bout of intermittent vapor exposure, mice exhibited an increase in HICs, when compared with their own baseline scores or the air controls. Conclusions: Intermittent alcohol vapor exposure significantly increased alcohol intake and produced signs of physical dependence. Initial pharmacological studies suggest that manipulation of the CRF system in the CeA can block this increased alcohol intake.

The γ-Aminobutyric Acid-B Receptor Agonist Baclofen Attenuates Responding for Ethanol in Ethanol-Dependent Rats

Abstract: Background: γ-Aminobutyric acid-B (GABAB) receptor agonists have been shown to suppress operant self-administration of ethanol in nondependent rats. However, little work has focused on the effects of GABAB receptor agonists on self-administration of ethanol in dependent animals. Methods: In the present experiment, the GABAB receptor agonist baclofen was tested for the ability to modulate both fixed- (FR) and progressive-ratio (PR) responding for ethanol in rats while nondependent and subsequently after ethanol dependence induction. Following the acquisition and stabilization of baseline operant ethanol self-administration and after dependence induction, baclofen [0.0, 0.5, 1, 2, and 4 mg/kg, intraperitoneal (IP)] was tested on FR-1 responding for ethanol. The ability of baclofen (2.0 mg/kg) to affect responding under a PR schedule of reinforcement was also evaluated. Dependence was induced in the animals by subjecting them to a 1-month intermittent vapor-exposure period in which animals were exposed to ethanol vapor for 14 h/d. Following the 1-month period, the vapor-exposed animals resumed FR-1 and PR baclofen drug testing (doses as described above) in the operant chambers at a time point corresponding to the animals being 6 hours into withdrawal (i.e., 6 hours after the ethanol vapor had been discontinued for that day). Results: Baclofen (0.0, 0.5, 1, 2, and 4 mg/kg, IP) dose-dependently decreased ethanol self-administration in both nondependent and dependent rats on a FR schedule of reinforcement. However, the dose of baclofen that significantly reduced responding for ethanol was shifted to the left in the ethanol vapor-exposed animals, indicating an increased sensitivity to baclofen in animals that were chronically exposed to ethanol. When tested using a PR schedule of reinforcement, there was a significant increase in the breakpoint for the vapor-exposed animals (i.e., the animals were willing to work more in a dependent state). Baclofen (2.0 mg/kg, IP) suppressed intake for both nondependent and dependent animals. Conclusions: Ethanol dependence produced increased self-administration of ethanol as reflected in increased ethanol intake and increased responding on a PR schedule of reinforcement. As baclofen suppressed ethanol self-administration and showed evidence of increased potency in dependent animals, the present experiment suggests that the GABAB receptor could be a potential pharmacotherapeutic target for the treatment of chronic alcoholism.

Time course of elevated ethanol intake in adolescent relative to adult rats under continuous, voluntary-access conditions.

Abstract: The Transition through adolescence is a unique developmental period. It is characterized by numerous behavioral, hormonal, and neural changes in humans as well as nonhuman mammals (see Spear, 2000 for a review). Among the behaviors characteristic of both human adolescents (Arnett, 1992; Maggs et al., 1995) as well as adolescent rodents (Primus and Kellogg, 1989; Spear et al., 1980; Vanderschuren et al., 1997) are increases in risk-taking and peer-directed social interactions. Drug and alcohol experimentation also becomes common among human adolescents during this time. The prevalence of alcohol use and misuse is surprisingly high in this age group, with 80% of 12th graders reporting having tried alcohol at least once and almost 30% of them reporting binge consumption within the past 2 weeks (Johnston et al., 2001). This high rate of alcohol use may have implications for development of later alcohol use disorders. Although causality cannot be inferred from these data, the results from the National Longitudinal Alcohol Epidemiological Survey found that initiation of alcohol use before the age of 14 increased the rate of lifetime alcohol dependency to 40%, whereas the rate was only 10% in those initiating use after the age of 20 (Grant and Dawson, 1997). As ethical constraints limit investigation of factors that contribute to elevated alcohol consumption during adolescence in humans, animal models of ethanol (EtOH) intake during adolescence are of importance. In a rat model, postnatal days (P)28 to 42 have been conservatively defined as prototypic adolescence based on characteristic neurobehavioral changes, with some signs of adolescence persisting in male adolescents until P55 to 60 (Spear, 2000). This time period itself may not be homogeneous, and can be further subdivided functionally into early, mid, and late phases (see Adriani et al., 2002; Varlinskaya and Spear, 2004, 2006a). Support for distinct subphases within the broader adolescent period includes the literature describing differential behavioral sensitivity to ethanol and other drugs of abuse during early versus late adolescence (see Adriani et al., 2002; Belluzzi et al., 2004; Silveri and Spear, 1998; Varlinskaya and Spear, 2006a). For instance, when examining hypnotic effects following challenge with a high dose of ethanol, early adolescent Sprague–Dawley rats were found to recover more rapidly from ethanol-induced sedation than late adolescent animals (Silveri and Spear, 1998). Similarly, early adolescent Sprague–Dawley rats (P28) were found to be more sensitive to ethanol-induced social facilitation in a familiar environment and less sensitive to the anxiolytic effects of ethanol in an unfamiliar environment than their late adolescent (P42) counterparts (Varlinskaya and Spear, 2006a). Although few studies using animal models have compared voluntary ethanol intake in adolescents and adults, several of the available studies have reported that elevated ethanol consumption is not limited to human adolescents (Doremus et al., 2005; Lancaster et al., 1996). In other studies, however, relatively moderate levels of voluntary ethanol intake have been reported in adolescent Long–Evans rats (Honey and Galef, 2003; Siciliano and Smith, 2001), although these studies were not designed to directly compare adolescent ethanol consumption with that of adults. Methodological differences across experiments may contribute to the mixed results observed in the literature. Previous research within our laboratory (Doremus et al., 2005) has repeatedly found that adolescent Sprague–Dawley rats voluntarily consume more ethanol than adults on a gram per kilogram basis, with adolescent intake tending to decline over the course of the 1 to 2-week assessment period while remaining significantly higher than that of adults. However, various environmental and procedural variables have been shown to exert notable influences on this intake (Doremus et al., 2005). For instance, in a home cage, 2-bottle choice paradigm, ethanol intake of adolescents was found to be insensitive to the intake-suppressing effect of single housing seen in adults, with adolescent animals drinking similar amounts of ethanol regardless of experimental housing condition (Doremus et al., 2005). Similarly, in a study examining postweaning housing conditions and initiation of ethanol-drinking procedure, McKinzie et al. (1998) found that neither postweaning housing condition nor initiation procedure affected levels of ethanol consumption in periadolescent alcohol-preferring (P) rats. In contrast, ethanol intake among adolescent, but not adult Sprague–Dawley rats, was found to be exacerbated when the solution was presented in ball-bearing–containing ball-point (BP) sipper tubes rather than open-ended tubes, with adolescents drinking from BP tubes developing a preference for ethanol over water (Doremus et al., 2005). Elevated ethanol intake among adolescents was also shown in this study not to be due to the inherent high caloric value of the ethanol solution. Despite evidence that early alcohol exposure is correlated with later alcohol dependency and alcohol use disorders in humans (Dewit et al., 2000; Grant and Dawson, 1997), there have been relatively few studies in laboratory animals examining the impact of chronic adolescent ethanol exposure on later consumption in adulthood in outbred animals. Studies looking at ethanol exposure during adolescence and later ethanol drinking in adulthood have found mixed results. Male periadolescent BALB/cByJ mice given a 2-bottle choice access to ethanol were found to have increased ethanol preference in adulthood (Blizard et al., 2004). Studies examining free-choice ethanol exposure during adolescence and later operant self-administration of ethanol in adulthood in P rats have found that P rats exposed during adolescence learned to self-administer ethanol more rapidly in adulthood and displayed more ethanol-seeking behavior as adults than naive P rats (Rodd-Henricks et al., 2002a). In a companion study, adult P rats given free-choice pre-exposure beginning in adulthood and later tested after a comparable amount of time did not show increased ethanol seeking in an operant paradigm (Rodd-Henricks et al., 2002b). In another study comparing 24-hour drinking patterns of adolescent and adult P rats over a 4-week period, adolescent male rats were found to exhibit more of an increase in ethanol licking behavior across weeks than adult males (Bell et al., 2006). High-alcohol–drinking rats (HAD) given 2-bottle choice access to ethanol solutions and water throughout adolescence and early adulthood (P30–60) also showed increased consumption (g/kg/d) and preference for ethanol over time (Bell et al., 2004). However, forced administration via ethanol vapor or forced consumption during adolescence did not result in increased intake in adult Sprague–Dawley rats (Slawecki and Betancourt, 2002; Tolliver and Samson, 1991). Most of these studies exposing animals to ethanol during adolescence assessed ethanol-drinking behavior in adulthood after a period of abstinence in postadolescence or early adulthood and did not include an adult comparison group or, alternatively, were conducted in animals bred to prefer alcohol. The purpose of the present study was to examine the time course and pattern of elevated ethanol intake seen in adolescent animals and during the adolescent-to-adult transition in outbred animals using a continuous access, 2-bottle choice paradigm, and to contrast this intake with ontogenetic patterns of food and water intake. By comparing intake in adulthood of animals initially given access to ethanol in adolescence with those whose initial experiences with ethanol began in adulthood, these studies were also designed to determine whether extended home cage access to ethanol during adolescence elevates subsequent rates of voluntary ethanol drinking in adulthood.

A functional polymorphism of the mu-opioid receptor gene (OPRM1) influences cue-induced craving for alcohol in male heavy drinkers.

Abstract: Background: The μ-opioid receptor gene (OPRM1) codes for the μ-opioid receptor, which binds β-endorphin. The A118G polymorphism in this gene affects β-endorphin binding such that the Asp40 variant (G allele) binds β-endorphin 3 times more tightly than the more common Asn40 variant (A allele). This study investigated the influence of the A118G polymorphism on cue reactivity after exposure to an alcoholic beverage in male heavy drinkers. Methods: Participants were either homozygous for the A allele (n=84) or carrying at least 1 copy of the G allele (n=24). All participants took part in a cue-reactivity paradigm where they were exposed to water and beer in 3-minute trials. The dependent variables of main interest were subjective craving for alcohol, subjective arousal, and saliva production. Results: G allele carriers reported significantly more craving for alcohol than the A allele participants (as indicated by the within-subject difference in craving after beer vs after water exposure). No differences were found for subjective arousal and saliva. Both groups did not differ in family history of alcoholism. Participants with the G allele reported a significantly higher lifetime prevalence of drug use than participants homozygous for the A allele. Conclusions: A stronger urge to drink alcohol after exposure to an alcoholic beverage might contribute to a heightened risk for developing alcohol-related problems in individuals with a copy of the G allele. The G allele might also predispose to drug use in general.

Genuine episodic memory deficits and executive dysfunctions in alcoholic subjects early in abstinence

Abstract: Background: Chronic alcoholism is known to impair episodic memory function, but the specific nature of this impairment is still unclear. Moreover, it has never been established whether episodic memory deficit in alcoholism is an intrinsic memory deficit or whether it has an executive origin. Thus, the objectives are to specify which episodic memory processes are impaired early in abstinence from alcohol and to determine whether they should be regarded as genuine memory deficits or rather as the indirect consequences of executive impairments. Methods: Forty recently detoxified alcoholic inpatients at alcohol entry treatment and 55 group-matched controls underwent a neuropsychological assessment of episodic memory and executive functions. The episodic memory evaluation consisted of 3 tasks complementing each other designed to measure the different episodic memory components (learning, storage, encoding and retrieval, contextual memory, and autonoetic consciousness) and 5 executive tasks testing capacities of organization, inhibition, flexibility, updating, and integration. Results: Compared with control subjects, alcoholic patients presented impaired learning abilities, encoding processes, retrieval processes, contextual memory and autonoetic consciousness. However, there was no difference between the 2 groups regarding the storage capacities assessed by the rate of forgetting. Concerning executive functions, alcoholic subjects displayed deficits in each executive task used. Nevertheless, stepwise regression analyses showed that only performances on fluency tasks were significantly predictive of some of the episodic memory disorders (learning abilities for 40%, encoding processes for 20%, temporal memory for 21%, and state of consciousness associated with memories for 26%) in the alcoholic group. Discussion: At alcohol treatment entry, alcoholic patients present genuine episodic memory deficits that cannot be regarded solely as the consequences of executive dysfunctions. These results are in accordance with neuroimaging findings showing hippocampal atrophy. Moreover, given the involvement of episodic memory and executive functions in alcohol treatment, these data could have clinical implications.

Does the association between alcohol consumption and depression depend on how they are measured

Abstract: Background: Inconsistent findings regarding the relationship between alcohol consumption and depression, including whether the relationship is J-shaped or U-shaped, may be at least partly due to the types of measures used for both alcohol consumption and depression. Methods: We conducted a general population survey using random digit dialing (RDD) and computer-assisted telephone interviewing (CATI) with 6,009 males and 8,054 females aged 18 to 76 years. The survey included 4 types of alcohol measures (frequency, usual and maximum quantity per occasion, volume, and heavy episodic drinking) covering both the past week and the past year, and 2 types of depression measures (meeting DSM criteria for a clinical diagnosis of major depression, recent depressed affect). Results: The overall relationship between depression and alcohol consumption did not vary by gender or type of depression measure but did vary significantly by type of alcohol measure, with the strongest relationship found for heavy episodic drinking and high quantity per occasion. There were also significant gender interactions with both depression and alcohol measures, with females showing a stronger relationship than males when depression was measured as meeting the criteria for major depression and when alcohol consumption was measured as quantity per occasion or heavy episodic drinking. There was some evidence of a J-shaped relationship, that is, greater depression among abstainers compared with those who usually drank 1 drink and never drank as much as 5 drinks for both former drinkers and lifetime abstainers when depression was measured as recent symptoms of depression but the J shape was found only for former drinkers when depression was measured as meeting the criteria for major depression and did not reach statistical significance in some analyses. Conclusions: The results of the present study suggest that measurement and gender are key issues in interpreting findings on the relationship between alcohol and depression. First, depression is primarily related to drinking larger quantities per occasion, less related to volume, and unrelated to drinking frequency, and this effect is stronger for women than for men. Second, the overall relationship between depression and alcohol consumption is stronger for women than for men only when depression is measured as meeting a clinical diagnosis of major depression and not when measured as recent depressed affect. Finally, while there was some evidence that former drinkers had slightly higher rates of major depression and higher scores on recent depressed affect compared with light drinkers, there was no evidence that light drinking was protective for major depression when compared with lifetime abstainers, although light drinkers did report fewer recent symptoms of depressed affect.

Persistent impairment of hippocampal neurogenesis in young adult rats following early postnatal alcohol exposure.

Abstract: Background: Prenatal alcohol exposure can cause damage to the developing fetus with outcomes including growth deficiency, facial dysmorphology, brain damage, and cognitive and behavioral deficits. Smaller brains in children with FASD have been linked both with reduced cell proliferation in the developing CNS and with apoptotic cell loss of postmitotic neurons. Prenatal alcohol exposure in rodents during the period of brain development comparable to that of the first and second trimesters of human pregnancy persistently alters adult neurogenesis. Long-term effects of alcohol exposure during the third trimester equivalent, which occurs postnatally in the rat, on adult neurogenesis have not been previously reported. The goal of this study was to examine the effect of postnatal binge-like alcohol exposure on cell proliferation and neurogenesis in hippocampal dentate gyrus during adolescence and young adulthood. Methods: Male Long-Evans rat pups were assigned to 3 groups: alcohol-exposed (AE), sham-intubated (SI) or suckle control (SC). AE pups received ethanol in a milk formula in a binge manner (2 feedings, 2 hours apart, total dose 5.25 g/kg/day) on postnatal days (PD) 4–9. BrdU was injected every other day on PD30–50. Animals were perfused either on PD50 to examine cytogenesis and neurogenesis in hippocampal dentate gyrus at the end of BrdU injections or on PD80 to evaluate new cell survival. Dorsal hippocampal sections were immunostained for BrdU, a marker for proliferating cells, Ki67, endogenous marker of proliferation, and NeuN, a marker for mature neurons. Results: Binge-like alcohol exposure on PD4–9 significantly reduced the number of mature neurons in adult hippocampal dentate gyrus (DG) both on PD50 and PD80, without altering cumulative cytogenesis on PD50. In addition, the number of new neurons, that were generated between PD30 and 50, was further reduced after 30 days of survival in all 3 groups (SC, SI, and AE). Conclusions: These observations suggest that early postnatal binge alcohol exposure results in long-term deficits of adult hippocampal neurogenesis, providing a potential basis for the deficits of hippocampus-dependent behaviors reported for this model.

Acculturation and Alcohol Among Latino Adults in the United States: A Comprehensive Review

Abstract: Background: In light of the inconsistent evidence associating acculturation with drinking outcomes among Latinos in the United States, the current paper comprehensively reviews the literature on this topic. Methods: Studies were eligible for review if they (1) were published in a refereed journal, (2) were published in English, (3) sampled Latino/Hispanic adults aged 18+, (4) examined self-reported drinking behavior, alcohol-related problems, and/or alcohol abuse/dependence, and (5) reported original results or unique analyses from a larger dataset. The review includes only studies using composite scales of acculturation. Studies were identified via electronic databases (i.e., PSYCHINFO, ETOH, and PUBMED) using search terms, and combinations thereof, including "acculturat*,"alcohol*,"Latino," and "Hispanic." This search was supplemented by recursive checking and author searches. Thirty-two articles were identified and coded on methodological characteristics; results from 24 disaggregating genders and using appropriate outcomes were summarized. Results: Higher acculturation was very consistently associated with higher odds of drinking among women, even controlling for demographic covariates. The evidence for women also suggested associations between higher acculturation and heavier drinking on other outcomes, including total volume, drinking frequency, typical quantity, heavy/problem drinking, drinking problems, and abuse/dependence, despite some null results. Relationships were weaker and ambiguous among men. Some evidence suggested that highly acculturated men are (compared with peers low on acculturation) more prone to drink, and perhaps as a result, can show higher consumption and problems. However, results also implied that, among male drinkers, higher acculturation may be associated with a lighter drinking pattern. Important study limitations were identified, including low power, aggregation of nondrinkers with drinkers, restrictive sampling, measurement issues, and analytical issues. Conclusions: The pattern of results suggests important associations between acculturation and drinking outcomes-particularly for women-but conclusions are tempered by serious methodological limitations. The review urges further research, particularly large-scale, longitudinal studies, addressing these limitations. Language: en

Alcohol consumption during pregnancy in nonindigenous west Australian women.

Abstract: Background: High alcohol intake in pregnancy has been linked to abnormal fetal development. There are limited published data in Australia on standard drinks of alcohol consumed on a typical occasion during the periconceptional period or pregnancy. Methods: During 1995 to 1997, a 10% random sample of all nonindigenous women giving birth in Western Australia was surveyed 12 weeks after delivery (N=4,839). Women were asked questions about alcohol consumption in each of the 4 time periods: the 3 months before pregnancy and each trimester of pregnancy. Questions were framed to measure volume, frequency, and type of alcoholic beverage. Results: 46.7% of the women had not planned their pregnancy. Most women (79.8%) reported drinking alcohol in the 3 months before pregnancy, with 58.7% drinking alcohol in at least 1 trimester of pregnancy. The proportion of women consuming 1 to 2 drinks on a typical occasion did not change much during pregnancy, but the number of occasions declined. Although the proportion of women consuming more than 2 standard drinks on a typical occasion declined after the first trimester, 19.0% of women consumed this amount in at least 1 trimester of pregnancy and 4.3% of women consumed 5 or more standard drinks on a typical occasion in at least 1 trimester of pregnancy. In the first trimester of pregnancy, 14.8% of women drank outside the current Australian guideline for alcohol consumption in pregnancy, decreasing to 10% in the second and third trimesters. Conclusions: Women generally reduced their average alcohol consumption and the number of standard drinks on a typical occasion as their pregnancy progressed, although 10 to 14% were drinking outside current guidelines for pregnancy. It is important that all women of child-bearing age are aware, well before they consider pregnancy, of the risks of drinking alcohol during pregnancy so they can make informed decisions about their alcohol consumption in pregnancy.

Prenatal alcohol exposure affects frontal-striatal BOLD response during inhibitory control.

Abstract: Background: Prenatal alcohol exposure can lead to widespread cognitive impairment and behavioral dysregulation, including deficits in attention and response inhibition. This study characterized the neural substrates underlying the disinhibited behavioral profile of individuals with fetal alcohol spectrum disorders (FASD). Methods: Children and adolescents (ages 8–18) with (n 5 13) and without (n 5 9) histories of heavy prenatal alcohol exposure underwent functional magnetic resonance imaging while performing a response inhibition (go/no-go) task. Results: Despite similar task performance (mean response latency, performance accuracy, and signal detection), blood oxygen level-dependent (BOLD) response patterns differed by group. Region-of-interest analyses revealed that during portions of the behavioral task that required response inhibition, alcohol-exposed participants showed greater BOLD response across prefrontal cortical regions (including the left medial and right middle frontal gyri), while they showed less right caudate nucleus activation, compared with control participants. Conclusions: These data provide an account of response inhibition-related brain functioning in youth with FASD. Furthermore, results suggest that the frontal–striatal circuitry thought to mediate inhibitory control is sensitive to alcohol teratogenesis.

Intake of Energy Drinks in Association With Alcoholic Beverages in a Cohort of Students of the School of Medicine of the University of Messina

Abstract: Background: Energy drinks (ED) are a widely used group of beverages known for their stimulant effects on central nervous system (CNS). The main components of ED are caffeine, taurine, carbohydrates, glucuronolactone, inositol, niacin, pantenol, and b-complex vitamins. The studies evaluating the effects of ED describe improvements in attention and ⁄ or reaction times and indices of alertness. It has been also shown that combination of caffeine and glucose, fundamental constituents of ED, can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive demand. Moreover, the associated ingestion of alcohol and ED has recently been observed to be becoming more and more widespread. Methods: With the aim to know the habits and uses of students, we administered a questionnaire containing questions regarding ED drinking alone or in association with alcoholic beverages. Five hundred students of the School of Medicine of the University of Messina were interviewed, and 450 filled the questionnaire. Results: A total of 56.9% of students declared using ED. A great part of users (48.4%) associate frequently ED and alcohol. In particular, 35.8% of ED + alcohol users have used ED + alcohol more than 3 times in the last month. Distinguishing the users into 2 groups (users of ED + alcohol and users of both ED and ED + alcohol), we observed in the second group a major use of cocktail containing a mix of ED and alcoholic beverages. This difference between the 2 groups is less represented about the ingestion of ED + alcohol in the night. Conclusions: Our data indicate that association of ED + alcohol is very popular among students. This behavior can be dangerous. In fact, the combination of ED + alcoholic drinks can reduce adversive symptoms of alcohol intoxication including the depressant effects. As consequence, users of ED + alcoholic beverages might not feel the signs of alcohol intoxication, thus increasing the probability of accidents and ⁄ or favoring the possibility of development of alcohol dependence.

Ethnic disparities in clinical severity and services for alcohol problems: results from the National Alcohol Survey.

Abstract: Background: This study reports lifetime estimates of the extent of unmet need for alcohol services across the 3 largest ethnic groups in America, and examines factors that may contribute to ethnic differences in service use. Prior studies report mixed findings as to the existence of ethnic disparities in alcohol services, with some suggesting that minorities are over-represented in treatment settings. Methods: Drawing on the most recent National Alcohol Surveys, we compare rates and factors associated with the lifetime service use for alcohol problems among Whites, Blacks, and Hispanics who meet lifetime criteria for alcohol abuse or dependence. Results: While bivariate analyses revealed few ethnic differences in service use, there were significant differences by ethnicity in multivariate models that included alcohol problem severity and its interactions with ethnicity. At higher levels of problem severity, both Hispanics and Blacks were less likely to have utilized services than comparable Whites. Hispanics, on the whole, reported higher-severity alcohol problems than Whites. Yet, they were less likely to have received specialty treatment and multiple types of alcohol services, and were more likely to cite economic and logistical barriers as reasons for not obtaining care. Conclusions: Future efforts to study ethnic disparities in alcohol services should utilize analytic approaches that address potential confounding between ethnicity and other factors in service use, such as alcohol problem severity. Our findings suggest that Hispanics and Blacks with higher-severity alcohol problems may utilize services at lower rates than comparable Whites, and that, particularly for Hispanics, this may in part be attributable to financial and logistical barriers to care.

Treatments for Patients With Dual Diagnosis: A Review

Abstract: Background: Comorbid substance use and mental illness is prevalent and often results in serious consequences. However, little is known about the efficacy of treatments for patients with dual diagnosis. Methods: This paper reviews both the psychosocial and medication treatments for those diagnosed with a substance-related disorder and one of the following disorders: (a) depression, (b) anxiety disorder, (c) schizophrenia, (d) bipolar disorder, (e) severe mental illness, and (f) nonspecific mental illness. We made no restriction of study design to include all published studies, due to the dearth of studies on treatments of patients with dual diagnosis. Results: Fifty-nine studies were identified (36 randomized-controlled trials; RCT). Limited number of studies, especially RCTs, have been conducted within each comorbid category. This review did not find treatments that had been replicated and consistently showed clear advantages over comparison condition for both substance-related and other psychiatric outcomes. Conclusions: Although no treatment was identified as efficacious for both psychiatric disorders and substance-related disorder, this review finds: (1) existing efficacious treatments for reducing psychiatric symptoms also tend to work in dual-diagnosis patients, (2) existing efficacious treatments for reducing substance use also decrease substance use in dually diagnosed patients, and (3) the efficacy of integrated treatment is still unclear. This review provides a critique of the current state of the literature, identifies the directions for future research on treatment of dual-diagnosis individuals, and calls for urgent attention by researchers and funding agencies to conduct more and more methodologically rigorous research in this area.

Ethanol‐Associated Cues Produce General Pavlovian‐Instrumental Transfer

Abstract: Background: Conditioned stimuli are thought to play an important role in maintaining ethanol use and inducing relapse. Therefore, understanding the mechanisms through which such stimuli trigger ethanol seeking is of interest in the study and treatment of alcoholism. Methods: This series of experiments examined the impact of ethanol-associated cues on ethanol-seeking behavior using a Pavlovian-instrumental transfer design. Rats received Pavlovian training in which an auditory stimulus predicted ethanol (10%) delivery. In a separate instrumental training phase, animals were trained to press a lever for ethanol. In the test phase, the impact of the stimulus on instrumental performance was assessed in extinction by presenting the stimulus while animals were free to perform the lever-press response. Experiment 2 assessed the selectivity of the transfer effect; rats received training with 2 auditory stimuli which predicted either ethanol or sucrose (2%) delivery and were trained to perform 2 instrumental responses, one earning ethanol and the other earning sucrose. Finally, Experiment 3 examined the selectivity of PIT using 2 natural rewards (sucrose and polycose). Results: The results from Experiment 1 show that ethanol supports excitatory conditioning and that ethanol-associated cues facilitate instrumental performance for ethanol. When the selectivity of the transfer effect was examined in Experiment 2, the ethanol-paired stimulus was found to have a general excitatory effect on reward-seeking behavior, affecting both ethanol-directed and sucrose-directed responding equally. In contrast, the sucrose-paired stimulus had a selective effect, elevating sucrose-directed responding only. Experiment 3 confirms that selective transfer is observed when 2 natural rewards are used to reinforce responding. Conclusions: These data provide further evidence that ethanol-associated cues can drive ethanol-seeking behaviors. Because ethanol-associated cues also enhanced seeking behavior for a nonalcohol reward, these results additionally suggest that the modulation of reward-directed behaviors by cues associated with ethanol versus natural rewards may rely on different behavioral and neural mechanisms.

Conceptual and design essentials for evaluating mechanisms of change.

Abstract: Background: Considerable progress has been made toward the development of evidence-based treatments for a wide range of psychological disorders; however, little is known about the mechanisms through which these treatments actually lead to clinical change. Although the use of traditional randomized controlled treatment designs and tests of statistical mediation have significantly advanced understanding of psychological treatments, they are insufficient to test mechanisms of change. Method: This article outlines the conceptual and methodological requirements for evaluating mechanisms of change, highlights the importance of such a focus, and offers specific recommendations for research aimed at elucidating change mechanisms. Results and Conclusions: Conceptualizing and conducting studies that test mechanisms of change requires substantial modifications to traditional research designs, but doing so will significantly enhance scientific understanding as well as the efficiency and effectiveness of clinical interventions.

Orexigenic peptides and alcohol intake: differential effects of orexin, galanin, and ghrelin.

Abstract: Background: The question is which hypothalamic systems for food intake might play a role in ethanol intake and contribute to alcohol abuse. The peptide orexin was found to exhibit similar properties to galanin in its relation to dietary fat and may therefore be similar to galanin in having a stimulatory effect on alcohol intake. Methods: Rats were trained to drink 10% ethanol, implanted with brain cannulas, and then injected in the paraventricular nucleus (PVN), lateral hypothalamus (LH), or nucleus accumbens (NAc) with galanin, orexin-A, and for comparison, ghrelin. Ethanol, food, and water intake were measured at 1, 2, and 4 hours postinjection. Results: In the PVN, both orexin and galanin significantly increased ethanol intake, whereas ghrelin increased food intake. In the LH, orexin again induced ethanol intake, while ghrelin increased eating. In the NAc, orexin failed to influence ethanol intake but did stimulate food intake. Conclusions: In ethanol-drinking rats, injection of orexin or galanin into the appropriate locus in the hypothalamus induced significant ethanol intake instead of food intake. Ghrelin, as a positive control, failed to influence ethanol intake at the same hypothalamic sites. In the NAc, as an anatomical control, orexin augmented eating but not ethanol intake. Thus orexin and galanin in the hypothalamus selectively stimulated ethanol intake at sites where other studies have shown that both ethanol and fat increase expression of the endogenous peptides. Thus, a neural circuit that evolved with the capability to augment food intake is apparently co-opted by ethanol and may serve as a potential positive feedback circuit for alcohol abuse.

Brain Activation Elicited by Affectively Positive Stimuli Is Associated With a Lower Risk of Relapse in Detoxified Alcoholic Subjects

Abstract: Background: Stimuli that are regularly associated with alcohol intake (AI) may acquire incentive salience, while other reinforcers can be devalued. We assessed whether brain activation elicited by (1) alcohol associated, (2) affectively positive, and (3) negative versus neutral stimuli is associated with the subsequent risk of relapse. Methods: Twelve detoxified alcoholic subjects (6 women and 6 men) and 12 age-matched and gender-matched healthy control subjects were assessed with functional magnetic resonance imaging (fMRI) and a fast single-event paradigm using standardized affective and alcohol-associated pictures. Patients were followed for 6 months and AI was recorded. Results: In alcoholic subjects, compared with healthy control subjects, (1) alcohol-related versus neutral visual stimuli elicited increased activation in the prefrontal (PFC; BA 6 and 10) and cingulate cortex (BA 23 and 24), precuneus and adjacent parietal cortex; (2) positive versus neutral stimuli elicited increased activation in the anterior cingulate cortex (ACC; BA 24), PFC (BA 10), ventral striatum and thalamus; and (3) negative versus neutral stimuli elicited increased activation in the PFC (BA 10). Seven alcoholic subjects relapsed. Within the follow-up period of 6 months, the number of subsequent drinking days (DD) and the amount of AI were inversely correlated with brain activation elicited by positive versus neutral stimuli in the thalamus (DD: r=−0.63, p=0.03; AI: r=−0.63, p=0.03) and in the ventral striatum (DD: r=−0.60, p=0.04; AI: r=−0.48, p=0.11). Conclusions: In this study, brain activation elicited by briefly presented alcohol-associated stimuli was not associated with the prospective risk of relapse. Unexpectedly, alcoholic subjects displayed increased limbic brain activation during the presentation of affectively positive but not negative stimuli, which may reflect a protective factor in detoxified alcoholic subjects.

Attention-deficit/hyperactivity disorder risk for heavy drinking and alcohol use disorder is age specific.

Abstract: Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are theoretically at risk for alcoholism because of their behavioral profiles in early childhood (Pelham and Lang, 1993; Smith et al, 2002) Impulsivity, distractibility, hyperactivity, and, in general, cognitive and behavioral under-regulation describe the symptoms of ADHD as well as the larger construct of behavioral under-control implicated in alcoholism theory (Sher, 1991; Tarter et al, 1990; Zucker et al, 1995) Many longitudinal studies have found a prospective connection between these early-appearing behavioral traits and later alcohol-related outcomes (Caspi et al, 1996; Masse and Tremblay, 1997; Niemela et al, 2006; Tarter et al, 2004) However, empirical tests of the hypothesis that childhood ADHD diagnosis elevates risk for alcohol-related outcomes have produced inconsistent findings A failure to consider age specificity in the association may have contributed to the discrepancies in the literature

Surrogate alcohol: what do we know and where do we go?

Abstract: Background: Consumption of surrogate alcohols (i.e., nonbeverage alcohols and illegally produced alcohols) was shown to impact on different causes of death, not only poisoning or liver disease, and appears to be a major public health problem in Russia and elsewhere. Methods: A computer-assisted literature review on chemical composition and health consequences of “surrogate alcohol” was conducted and more than 70 references were identified. A wider definition of the term “surrogate alcohol” was derived, including both nonbeverage alcohols and illegally produced alcohols that contain nonbeverage alcohols. Results: Surrogate alcohol may contain substances that cause severe health consequences including death. Known toxic constituents include lead, which may lead to chronic toxicity, and methanol, which leads to acute poisoning. On the other hand, the role of higher alcohols (e.g., propanol, isobutanol, and isoamyl alcohol) in the etiology of surrogate-associated diseases is currently unclear. Whether other constituents of surrogates have contributed to the high all-cause mortality over and above the effect of ethanol in recent studies also remains unclear. Conclusions: Given the high public health importance associated with the consumption of surrogate alcohols, further knowledge on its chemical composition is required as well as research on its links to various disease endpoints should be undertaken with priority. Some interventions to reduce the harm resulting from surrogate alcohol could be undertaken already at this point. For example, the use of methanol or methanol-containing wood alcohol should be abolished in denatured alcohol. Other possible surrogates (e.g., automobile products) should be treated with bittering agents to avoid consumption.

Family-based association analyses of alcohol dependence phenotypes across DRD2 and neighboring gene ANKK1.

Abstract: Background: There is an extensive and inconsistent literature on the association of the dopamine D2 receptor gene (DRD2) with alcohol dependence. Conflicting results have been attributed to differences in the severity of the alcohol dependence phenotype across studies, failure to exclude related disorders from comparison groups, and artifacts of population-stratification. Recently the genetic polymorphism most widely analyzed in DRD2, Taq1A, has been discovered to reside in a neighboring gene, ankyrin repeat and kinase domain containing 1 (ANKK1), located 10 kb downstream from DRD2. Methods: To more carefully characterize evidence for association across this region, we genotyped 26 single nucleotide polymorphisms (SNPs) spanning DRD2 and ANKK1 in a sample of 219 Caucasian families (n = 1,923) from the Collaborative Study on the Genetics of Alcoholism (COGA), making this the most extensive analysis to date of association between this region and alcohol dependence. We used family-based analyses robust to population-stratification, and we made use of rich phenotypic data to analyze alcohol dependence and subtypes hypothesized in the literature to be more directly influenced by DRD2. Results: We found that the evidence for association is strongest in the 5′ linkage disequilibrium block of ANKK1 (that does not contain Taq1A), with weak evidence of association with a small number of SNPs in DRD2. The association in ANKK1 is strongest among the subsets of alcoholics with medical complications and with antisocial personality disorder. Conclusions: More extensive genotyping across DRD2 and ANKK1 suggests that the association with alcohol dependence observed in this region may be due to genetic variants in the ANKK1 gene. ANKK1 is involved in signal transduction pathways and is a plausible biological candidate for involvement in addictive disorders.

Moderators of Naltrexone’s Effects on Drinking, Urge, and Alcohol Effects in Non‐Treatment‐Seeking Heavy Drinkers in the Natural Environment

Abstract: Background: Naltrexone (NTX) has proven to be effective with alcoholics in treatment, with most controlled clinical trials showing beneficial effects on heavy drinking rates. However, little is known about the behavioral mechanisms underlying the effects of NTX on drinking, or about patient characteristics that may moderate NTX's effects on drinking. In this study, ecological momentary assessment (EMA) techniques were used to investigate some of the putative mechanisms of naltrexone's effects on drinking in heavy drinkers who were not seeking treatment for alcohol problems. Polymorphisms in the D4 dopamine receptor (DRD4) gene and the μ-opiate receptor (OPRM1) gene, family history of alcohol problems, age of onset of alcoholism and gender were explored as potential moderators of NTX's effects. Methods: After a one-week placebo lead-in period, heavy drinkers (n = 180), 63% of whom were alcohol-dependent, were randomized to 3 weeks of daily naltrexone (50 mg) or placebo. Throughout the study, participants used EMA on palm-pilot computers to enter, in real time, drink data, urge levels, and subjective effects of alcohol consumption. Results: NTX reduced percentage drinking days in all participants and reduced percent heavy drinking days in DRD4-L individuals; NTX decreased urge levels in participants with younger age of alcoholism onset; NTX increased time between drinks in participants who had more relatives with alcohol problems; and NTX reduced the stimulating effects of alcohol in women. OPRM1 status did not moderate any of NTX's effects. Conclusions: These results confirm earlier findings of NTX's effects on drinking and related subjective effects, and extend them by describing individual difference variables that moderate these effects in the natural environment, using data collected in real time.

Encouraging posttreatment self-help group involvement to reduce demand for continuing care services: two-year clinical and utilization outcomes.

Abstract: Background: Accumulating evidence indicates that addiction and psychiatric treatment programs that actively promote self-help group involvement can reduce their patients' health care costs in the first year after treatment, but such initially impressive effects may wane over time. This paper examines whether the positive clinical outcomes and reduced health care costs evident 1 year after treatment among substance-dependent patients who were strongly encouraged to attend 12-step self-help groups were sustained at 2-year follow-up. Methods: A 2-year quasi-experimental analysis of matched samples of male substance-dependent patients who were treated in either 12-step–based (n=887 patients) or cognitive-behavioral (CB, n=887 patients) treatment programs. The 12-step–based programs placed substantially more emphasis on 12-step concepts, had more staff members “in recovery,” had a more spiritually oriented treatment environment, and promoted self-help group involvement much more extensively than did the CB programs. The 2-year follow-up assessed patients' substance use, psychiatric functioning, self-help group affiliation, and mental health care utilization and costs. Results: As had been the case in the 1-year follow-up of this sample, the only difference in clinical outcomes was a substantially higher abstinence rate among patients treated in 12-step (49.5%) versus CB (37.0%) programs. Twelve-step treatment patients had 50 to 100% higher scores on indices of 12-step self-help group involvement than did patients from CB programs. In contrast, patients from CB programs relied significantly more on outpatient and inpatient mental health services, leading to 30% lower costs in the 12-step treatment programs. This was smaller than the difference in cost identified at 1 year, but still significant ($2,440 per patient, p=0.01). Conclusions: Promoting self-help group involvement appears to improve posttreatment outcomes while reducing the costs of continuing care. Even cost offsets that somewhat diminish over the long term can yield substantial savings. Actively promoting self-help group involvement may therefore be a useful clinical practice for helping addicted patients recover in a time of constrained fiscal resources.

Decreased plasma brain-derived neurotrophic factor levels in patients with alcohol dependence.

Abstract: Background: Many reports have suggested possible relationships between brain-derived neurotrophic factor (BDNF) and alcohol dependence. A protective effect of BDNF against ethanol-induced cell damage has been suggested, and this effect may contribute to the development or maintenance of alcohol dependence. This study was carried out in order to verify the significance of BDNF in alcohol dependence. Methods: Peripheral BDNF levels were measured in alcohol-dependent patients and control subjects using an enzyme-linked immunosorbent assay. A physician’s interview and standardized questionnaire were used to obtain information regarding each patient’s history of alcohol consumption. Results: The mean BDNF level was lower in the alcohol dependence group (389.5 ± 501.7 pg/ml) than in the normal controls (822.5 ± 420.7 pg/ml) by analysis of covariance (ANCOVA) (F = 25.79, p < 0.01). The mean BDNF level was lower in the alcohol-dependent patients with a positive family history of alcohol dependence (247.6 ± 289.2 pg/ml) than in those with a negative family history of alcohol dependence (583.9 ± 652.8 pg/ml) by ANCOVA (F = 6.51, p = 0.01). The BDNF levels did not correlate significantly with any of the variables analyzed in this study, including Beck depression inventory, state and trait anxiety inventory (STAI-S and T), and various drinking behaviors. Conclusions: Changes in the levels of BDNF might play a role in the pathophysiology and inheritance of alcohol dependence.