The loss of metabolic control on alcohol drinking in heavy drinking alcohol-dependent subjects

Background

Most physiological studies interested in alcohol-dependence examined ethanol as a pharmacological agent rather than a nutrient. We conducted two studies, which assessed the metabolic and endocrine factors involved in the regulation of alcohol and nutrient intake in alcohol-dependent (AD) subjects. We also examined the potential role of a disruption in energy balance in alcohol-dependence.

Methods and Results

In Study-1, quantitative dietetic interviews of eating and drinking habits were conducted with 97 AD subjects. The population was split around a median alcohol intake value of 12.5 kcal/kg/day. The results showed that the “low alcohol” drinking AD subjects had high Body Mass Index (BMI) and Fat Mass (FM) and alcohol intake was compensated for by a decrease in non-alcoholic intakes. “High alcohol” drinking AD subjects, on the other hand, had low BMI and FM and the total caloric intakes were largely above norms. In Study-2, 24 AD inpatients were submitted to dietetic interviews, calorimetry and blood samplings for the measurement of biomarkers of the regulation of metabolism and satiety, on day 2, 5 and 16 of abstinence. These patients were compared with 20 controls matched for age and gender. We observed in AD patients an increase in cortisol, leptin and PYY plasma levels and a decrease in ghrelin, which might explain the observed decrease in non-alcoholic intakes. However, alcoholic and non-alcoholic intakes correlated positively with basal metabolism and negatively with leptin and leptin/BMI.

Conclusion

For individuals consuming below12.5 kcal/kg/day of alcohol, alcohol intake is compensated for by a decrease in non-alcoholic nutrient intakes, probably due to changes in metabolic and satiety factors. For individuals consuming above 12.5 kcal/kg/day of alcohol, alcohol accelerates metabolism and decreases fat mass and leptin levels, and the total caloric intake largely exceeds norms. A dual model for regulation of energy intake in AD subjects is proposed.     

Doctors' drinking habits and consumption of alcohol.

Alcohol consumption and drinking habits among Finnish doctors were studied as part of a survey of stress and burnout. A questionnaire containing 99 questions or groups of questions was sent to all 3496 practising doctors aged under 66 randomly selected from the registry of the Finnish Medical Association. Altogether 2671 doctors (76%) responded; this sample was representative of the Finnish medical profession. The average weekly consumption of alcohol during the past year and various aspects of drinking behaviour were assessed, and the presence or absence of symptoms and diseases often encountered among heavy drinkers and addicts was determined. The data were analysed separately for men and women, for those aged less than or equal to 40 and greater than 40, and for the men with high and low alcohol consumption and with high and low scores on the index of drinking habits. Selected variables related to work, stress, and coping were correlated with alcohol consumption and drinking behaviour. The median consumption of alcohol among male doctors was 4876 g (6.2 litres) and among female doctors 2226 g (2.8 litres) of absolute alcohol per person per year and was higher in those aged over 40. Beer was most commonly drunk by men and wine by women. Increased alcohol consumption was associated with older age, disappointment with career, heavy smoking, use of benzodiazepines, stress and burnout symptoms, suicidal thoughts, general dissatisfaction, and diseases related to alcohol. Drinking habits were heavier among doctors working in community health centres, those taking long sick leaves, younger doctors disappointed with their careers or the atmosphere at work, and older doctors immersed in their work. Alcohol consumption among doctors seems to be higher than that of the general population in Finland, and heavy drinking seems to be associated with stress and burnout.     

Cross-cultural patterns in dynamic ratings of positive and negative natural emotional behaviour

Background

Studies of cross-cultural variations in the perception of emotion have typically compared rates of recognition of static posed stimulus photographs. That research has provided evidence for universality in the recognition of a range of emotions but also for some systematic cross-cultural variation in the interpretation of emotional expression. However, questions remain about how widely such findings can be generalised to real life emotional situations. The present study provides the first evidence that the previously reported interplay between universal and cultural influences extends to ratings of natural, dynamic emotional stimuli.

Methodology/Principal Findings

Participants from Northern Ireland, Serbia, Guatemala and Peru used a computer based tool to continuously rate the strength of positive and negative emotion being displayed in twelve short video sequences by people from the United Kingdom engaged in emotional conversations. Generalized additive mixed models were developed to assess the differences in perception of emotion between countries and sexes. Our results indicate that the temporal pattern of ratings is similar across cultures for a range of emotions and social contexts. However, there are systematic differences in intensity ratings between the countries, with participants from Northern Ireland making the most extreme ratings in the majority of the clips.

Conclusions/Significance

The results indicate that there is strong agreement across cultures in the valence and patterns of ratings of natural emotional situations but that participants from different cultures show systematic variation in the intensity with which they rate emotion. Results are discussed in terms of both ‘in-group advantage’ and ‘display rules’ approaches. This study indicates that examples of natural spontaneous emotional behaviour can be used to study cross-cultural variations in the perception of emotion.     

Exploration of environmental changes relates to lifestyle

Decision making in informed animals is often described by optimalitymodels. However, how information about an environment is acquiredis rarely investigated. Cost/benefit considerations suggestthat species differ in this respect according to their lifestyle.We tested the hypothesis that resident species react to changesin their familiar environment earlier and explore it more intensivelythan do nomadic species by observing the response to environmentalchanges (presentation of novel objects) in 10 parrot species.Phylogenetic relationships were taken into account. Residentstouched the novel objects significantly earlier and exploredmore objects than did nomads. In addition, species with a highproportion of fruits in their food spectrum explored more thandid species with other food preferences. The results are inaccordance with different costs and benefits of informationgathering for species that differ in their lifestyle and ecologicaldemands.     

Rats bred for high alcohol drinking are more sensitive to delayed and probabilistic outcomes

Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be because of factors that predate drug exposure (e.g. genetics). This study examined the role of genetics by comparing impulsivity measures in ethanol-naive rats selectively bred based on their high [high alcohol drinking (HAD)] or low [low alcohol drinking (LAD)] consumption of ethanol. Replicates 1 and 2 of the HAD and LAD rats, developed by the University of Indiana Alcohol Research Center, completed two different discounting tasks. Delay discounting examines sensitivity to rewards that are delayed in time and is commonly used to assess 'choice' impulsivity. Probability discounting examines sensitivity to the uncertain delivery of rewards and has been used to assess risk taking and risk assessment. High alcohol drinking rats discounted delayed and probabilistic rewards more steeply than LAD rats. Discount rates associated with probabilistic and delayed rewards were weakly correlated, while bias was strongly correlated with discount rate in both delay and probability discounting. The results suggest that selective breeding for high alcohol consumption selects for animals that are more sensitive to delayed and probabilistic outcomes. Sensitivity to delayed or probabilistic outcomes may be predictive of future drinking in genetically predisposed individuals.     

Auditory affective norms for German: testing the influence of depression and anxiety on valence and arousal ratings

Background

The study of emotional speech perception and emotional prosody necessitates stimuli with reliable affective norms. However, ratings may be affected by the participants'' current emotional state as increased anxiety and depression have been shown to yield altered neural responding to emotional stimuli. Therefore, the present study had two aims, first to provide a database of emotional speech stimuli and second to probe the influence of depression and anxiety on the affective ratings.

Methodology/Principal Findings

We selected 120 words from the Leipzig Affective Norms for German database (LANG), which includes visual ratings of positive, negative, and neutral word stimuli. These words were spoken by a male and a female native speaker of German with the respective emotional prosody, creating a total set of 240 auditory emotional stimuli. The recordings were rated again by an independent sample of subjects for valence and arousal, yielding groups of highly arousing negative or positive stimuli and neutral stimuli low in arousal. These ratings were correlated with participants'' emotional state measured with the Depression Anxiety Stress Scales (DASS). Higher depression scores were related to more negative valence of negative and positive, but not neutral words. Anxiety scores correlated with increased arousal and more negative valence of negative words.

Conclusions/Significance

These results underscore the importance of representatively distributed depression and anxiety scores in participants of affective rating studies. The LANG-audition database, which provides well-controlled, short-duration auditory word stimuli for the experimental investigation of emotional speech is available in Supporting Information S1.     

Intentional modulation of the late positive potential in response to smoking cues by cognitive strategies in smokers

Attentional bias is considered an important concept in addiction since it has been found to correlate with subjective craving and is strongly associated with relapse after periods of abstinence. Hence, investigating in ways to regulate attention for drug cues would be of major clinical relevance. The present study examined deliberate, cognitive modulation of motivated attention for smoking cues in smokers. The effects of three different reappraisal strategies on an electrophysiological measure of attentive processing were investigated. Early and late LPP components in response to passively viewed neutral and smoking pictures were compared with LPPs in response to smoking pictures that were reappraised with three different reappraisal strategies. Results show that when smokers actively imagine how pleasant it would be to smoke (pleasant condition), their early LPP in response to smoking cues increases, but when smokers actively focus on an alternative stimulus (distraction condition) or think of a rational, uninvolved interpretation of the situation (rational condition), smoking-related late LPP amplitude decreases to the processing level of neutral stimuli. Present results are the first to indicate that smoking cue-elicited LPP amplitudes can be modulated by cognitive strategies, suggesting that attentive processing of smoking cues can be intentionally regulated by smokers with various levels of dependence. Although cognitive strategies can lead to enhanced processing of smoking cues, it is not completely clear whether cognitive strategies are also successful in reducing smoking-related motivated attention. Although findings do point in this direction, present study is best considered preliminary and a starting point for other research on this topic. A focus on the distraction strategy is proposed, as there are indications that this strategy is more successful than the rational strategy in decreasing LPP amplitude.     

The effect of visual cues on difficulty ratings for segregation of musical streams in listeners with impaired hearing

Background

Enjoyment of music is an important part of life that may be degraded for people with hearing impairments, especially those using cochlear implants. The ability to follow separate lines of melody is an important factor in music appreciation. This ability relies on effective auditory streaming, which is much reduced in people with hearing impairment, contributing to difficulties in music appreciation. The aim of this study was to assess whether visual cues could reduce the subjective difficulty of segregating a melody from interleaved background notes in normally hearing listeners, those using hearing aids, and those using cochlear implants.

Methodology/Principal Findings

Normally hearing listeners (N = 20), hearing aid users (N = 10), and cochlear implant users (N = 11) were asked to rate the difficulty of segregating a repeating four-note melody from random interleaved distracter notes. The pitch of the background notes was gradually increased or decreased throughout blocks, providing a range of difficulty from easy (with a large pitch separation between melody and distracter) to impossible (with the melody and distracter completely overlapping). Visual cues were provided on half the blocks, and difficulty ratings for blocks with and without visual cues were compared between groups. Visual cues reduced the subjective difficulty of extracting the melody from the distracter notes for normally hearing listeners and cochlear implant users, but not hearing aid users.

Conclusion/Significance

Simple visual cues may improve the ability of cochlear implant users to segregate lines of music, thus potentially increasing their enjoyment of music. More research is needed to determine what type of acoustic cues to encode visually in order to optimise the benefits they may provide.     

Adolescent binge drinking leads to changes in alcohol drinking, anxiety, and amygdalar corticotropin releasing factor cells in adulthood in male rats

Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (~postnatal days 28-42) in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF) cell in the lateral portion of the central amygdala (CeA), a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity), an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects with implications for anxiety and alcohol use disorders.     

A content analysis of views of self-control: Relation to positive and negative valence,and implications for a working definition

It has been argued that one important variable that hampers research on self-control strategies is the absence of a working definition of self-control. Part of the difficulty involves the ambiguous and self-reflexive nature of the term itself, and part of the difficulty involves tautological imprecision equating the construct and definition of self-control with the effects of a self-control strategy. In order to begin to bring order to what has heretofore been a linguistic morass, an effort was made to assess individuals' views of self-control and then to perform a content analysis of the different aspects and dimensions actually embedded within these views. This study offered partial confirmation for six previously identified dimensions: choice, responsibility, awareness, discipline, skill, and goal. These dimensions provide us with a beginning phenomenological framework for assessing how individuals view self-control, and thereby help refine the position endorsed by Mahoney and Arnkoff (1979) that “self-control is a social label which is differentially applied to some behavior patterns.” Further, individuals were requested to list positive and negative aspects of self-control, in order to assess whether, as Mahoney and Arnkoff suggest, self-control is necessarily applied to behavior perceived as (a) being socially appropriate or desirable and (b) originating from noble ideals. The study found that there were both positively and negatively valenced aspects thought to be associated with self-control, and that the mention of a certain dimension of self-control (discipline) was found to be significantly correlated with a specific negatively valenced view (rigidity). The study concludes with implications for developing a working definition of self-control, and with guidelines and suggestions for future research.     

Effect of alcohol drinking and cigarette smoking on neutrophil functions in adults

In recent years, the effects of smoking and excessive alcohol consumption on immune function have been studied, due to a high prevalence of infection or cancer in heavy drinkers, and the combination of smoking and drinking was considered to be a carcinogenic risk. However, the effect of smoking and drinking on systemic immune function has yet to be clearly understood. In this study, we investigated neutrophil functions (reactive oxygen species (ROS) productive activity, phagocytic ability and serum opsonic activity) and their relationship with alcohol consumption or amount of smoking. In total there were 731 male and female adult subjects who participated in the Iwaki Health Promotion Project in 2005. Multiple regression analysis showed a trend of increased ROS production in male subjects and a statistically significant decrease was observed in phagocytic activity caused by smoking in female subjects. In other words, oxidative stress caused by smoking in male subjects may be involved in ROS production from neutrophils. Decreased phagocytic activity of neutrophils caused by smoking suggests that host defense functions were impaired in female subjects. A relationship between neutrophil functions and the amount of alcohol consumption was not observed. Copyright © 2011 John Wiley & Sons, Ltd.     

The contributions of BMP4, positive guidance cues, and repulsive molecules to cutaneous nerve formation in the chick hindlimb

Our previous surgical manipulations have shown that the target ectoderm is necessary for the initial formation of one of the major cutaneous nerves in the embryonic chick limb (Honig, M.G., Camilli, S.J., Xue, Q.S., 2004. Ectoderm removal prevents cutaneous nerve formation and perturbs sensory axon growth in the chick hindlimb. Dev. Biol. 266, 27-42.). Moreover, the target ectoderm is required during a critical time period, at approximately St. 24, when those axons are about to diverge from the hindlimb plexus. To elucidate the underlying mechanisms, here we examined the effects of removing the ectoderm at St. 24 on a variety of molecules expressed within the limb. We find that, while ectoderm removal is accompanied by changes in the expression of Lmx1, fibronectin, EphA7, cDermo-1, and in the complement of muscle cells, these changes do not account for the cutaneous nerve deficit. In contrast, an upregulation of PNA-binding sites and a downregulation of Bmp4 appear to be associated with this nerve deficit. Exogenous BMP4 reversed the effect of ectoderm removal on cutaneous nerve formation, but did not act as a chemoattractant. Our results suggest that BMP4, together with permissive and repulsive molecules that growing cutaneous axons encounter in the local environment and with signaling molecules, originating from and/or dependent on the ectoderm, work in concert to ensure proper cutaneous nerve formation.     

Pharmacological characterization of the nociceptin receptor which mediates reduction of alcohol drinking in rats

Chronic intracerebroventricular (ICV) treatment with nociceptin/orphanin FQ (NC), the endogenous ligand for the opioid receptor-like 1 (ORL1) receptor, reduces ethanol intake in alcohol-preferring rats and abolishes the rewarding properties of ethanol in the place conditioning paradigm. To pharmacologically characterize the receptor involved, the present study evaluated the effect on ethanol drinking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats of ICV injections for 8 days of NC or of the NC analogs NC(1-17)NH(2), NC(1-13)NH(2), NC(1-12)NH(2) and [Nphe(1)]NC(1-13)NH(2). In vitro studies indicate that NC, NC(1-17)NH(2), NC(1-13)NH(2) and NC(1-12)NH(2) are agonists, while [Nphe(1)]NC(1-13)NH(2) is a selective antagonist at the ORL1 receptor. Freely feeding and drinking rats were offered 10% ethanol 30 min/day at the beginning of the dark phase of the light cycle. NC significantly attenuated ethanol intake at 500 or 1000 ng/rat (210 or 420 pmol/rat). NC(1-17)NH(2), markedly reduced ethanol intake, but its effect was statistically significant at 1000 (420 pmol/rat), not at 500 ng/rat (210 pmol/rat). After the end of treatment ethanol drinking promptly came back to baseline level. Ethanol consumption was also reduced by NC(1-13)NH(2); however, its effect was less potent and pronounced. NC(1-12)NH(2) did not modify ethanol intake at doses up to 4000 ng/rat (2339 pmol/rat). Water and food consumption were not modified. Treatment with [Nphe(1)]NC(1-13)NH(2), 66 or 99 microg/rat, did not modify ethanol intake; however, [Nphe(1)]NC(1-13)NH(2), 66 microg/rat, given just before 1000 ng/rat of NC(1-17)NH(2), abolished the effect of the agonist. The present results show that the 13 amino acid N-terminal sequence of NC is essential for the effect on ethanol intake and indicate that [Nphe(1)]NC(1-13)NH(2) acts as an antagonist to block the effect of NC. These findings provide further evidence that selective agonists at the ORL-1 receptor attenuate ethanol intake in alcohol-preferring rats and suggest that the NC/ORL1 system may represent an interesting target for treatment of alcohol abuse.     

Effect of chronic vasopressin treatment on alcohol drinking of Brattleboro HZ and DI rats

Preference for alcohol was determined for three groups of male and female rats, 100–150 days old, comprised of: (1) Long Evans (LE); (2) LE-derived Brattleboro heterozygous (HZ); and (3) Brattleboro homozygous (DI) animals afflicted with diabetes insipidus due to vasopressin deficiency. Each alcohol drinking test was run over 11 days during which food, water and an ethyl alcohol solution, increased in concentration from 3% to 25%, were freely available. Following an initial preference screen, 100 milli-units of vasopressin tannate in oil was administered subcutaneously, during a second preference test, once per day to each animal. This treatment ameliorated the polydipsia-polyuria syndrome characteristic of the DI sub-strain of Brattleboro rat. Administration of the peptide to both the LE or HZ animals exerted no effect on g/kg intake nor on the proportional measure of alcohol to water. However, in the DI rat of either gender, vasopressin reduced the mean absolute gram intake of alcohol over concentrations to resemble that of the other LE and/or HZ groups. These results demonstrate that vasopressin serves to normalize the intake of alcohol in the DI rat by virtue of the elimination of the diabetic condition. However, since vasopressin fails to alter alcohol consumption of the HZ and LE rats, it would appear that this neuroactive peptide may play only a minor role in the CNS mechanisms governing the voluntary selection of alcohol.     

Synthesis of a hexasaccharide that relates to the arabinogalactan epitope.

A hexasaccharide derivative of the arabinogalactan epitope, methyl beta-D-galactopyranosyl-(1-->6)-[alpha-L-arabinofuranosyl-(1-->3)]-beta-D-galactopyranosyl-(1-->6)-beta-D-galactopyranosyl-(1-->6)-[alpha-L-arabinofuranosyl-(1-->3)]-alpha-D-galactopyranoside, was synthesized efficiently using a 3+3 strategy. The key step is the preparation of the trisaccharide donor, isopropyl 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->6)-[2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosyl-(1-->3)]-2,4-di-O-benzoyl-1-thio-beta-D-galactopyranoside, from isopropyl 1-thio-beta-D-galactopyranoside using a one-pot synthesis of a 3,6-differentially protected building block.     

The replicability of QTLs for murine alcohol preference drinking behavior across eight independent studies

On the basis of eight independent quantitative trait loci (QTL) studies of ethanol (alcohol) preference drinking in mice, a meta-analysis was carried out to examine the replicability of QTLs across studies and to enhance the power of QTL detection and parameter estimation. To avoid genetic heterogeneity, we analyzed only studies of mapping populations derived from the C57BL/6 (B6) and DBA/2 (D2) inbred progenitor strains. Because these studies were carried out in five different laboratories, there were substantial differences in testing procedure, data analysis, and especially in the choice of mapping population (BXD recombinant inbred strains, F₂, backcross, selected lines, or congenic strains). Despite this, we found several QTLs that were sufficiently robust as to appear consistently across studies given the strengths and weaknesses of the mapping populations employed. These were on Chromosomes (Chrs) 2 (proximal to mid), 3 (mid to distal), 4 (distal), and 9 (proximal to mid). The P value for each of these QTLs, combined across all applicable studies, ranged from 10⁻⁷ to 10⁻¹⁵, with the additive effect of each QTL accounting for 3–5% of the trait variance extrapolated to an F₂ population. Two other QTLs on Chrs 1 (distal) and 11 (mid) were less consistent, but still reached overall significance (P < .0001). Received: 18 April 2001 / Accepted: 25 July 2001