Nonalcoholic Controls Research Articles

Widespread effects of alcohol on white matter microstructure.

Evidence suggests that chronic misuse of alcohol may preferentially affect the integrity of frontal white matter (WM) tracts, which can impact executive functions important to achieve and maintain abstinence. Global and regional WM microstructure was assessed using diffusion magnetic resonance measures of fractional anisotropy (FA) for 31 abstinent alcoholics (ALC) with an average of 25years of abuse and approximately 5years of sobriety and 20 nonalcoholic control (NC) participants. Data processing was conducted with FreeSurfer and FSL processing streams. Voxelwise processing of the FA data was carried out using tract-based spatial statistics. Clusters of significance were created to provide a quantitative summary of highly significant regions within the voxelwise analysis. Widespread, bilateral reductions in FA were observed in ALC as compared to NC participants in multiple frontal, temporal, parietal, and cerebellar WM tracts. FA in the left inferior frontal gyrus was associated with drinking severity. This study found widespread reductions in WM integrity in a group of ALC compared to NC participants, with most pronounced effects in frontal and superior tracts. Decreased FA throughout the frontostriatal circuits that mediate inhibitory control may result in impulsive behavior and inability to maintain sobriety.

Lower [3H]Citalopram binding in brain areas related to social cognition in alcoholics.

In the present study, putative alterations in the serotonin transporter density were evaluated in anterior and posterior insula, posterior cingulate cortex, dorsolateral and dorsomedial prefrontal cortex, hippocampus, parahippocampal gyrus and dorsal raphe nucleus in Cloninger type 1 (n = 9) and type 2 (n = 8) alcoholics and non-alcoholic controls (n = 10). Human whole-hemisphere autoradiography was used to measure [3H]citalopram binding to serotonin transporters in eight brain areas in all post-mortem brains. Significant differences were observed in the mean [3H]citalopram binding between the study groups, with antisocial type 2 alcoholics showing the lowest binding. Differences between the study groups were prominent in the posterior insula and posterior cingulate cortex, where both alcoholic groups had low [3H]citalopram binding, and in the parahippocampal gyrus where only antisocial type 2 alcoholics had low [3H]citalopram binding when compared with non-alcoholic controls. Although these data are preliminary, and from relatively small diagnostic groups, these results show that alcoholics may have lower serotonergic tone in the brain, thus decreasing social cognition and increasing alcohol-cue reactivity.

Evidence of genotoxicity in lymphocytes of non-smoking alcoholics.

Alcohol abuse is a significant public health issue. Epidemiological studies conducted on different populations consistently showed that consumption of alcoholic beverages is associated with cytogenetic damages and higher risk for several types of cancer. However, the interpretation of many cytogenetic studies resulted complicated because some confounding factors, such as smoking habit, are not always taken into account. In the present study, the frequency of sister chromatid exchanges (SCEs), chromosome aberrations (CAs) and micronuclei (MNs) in cultured human lymphocytes was assessed on 15 alcoholic and 15 non-alcoholic control male subjects. Moreover, considering the implication of the Glutathione S-transferases gene polymorphisms in the genetic susceptibility to alcoholic liver diseases, we considered an important issue to evaluate the relationship between these gene polymorphisms and the cytogenetic damage. In our sample we exclusively considered individuals that did not smoke nor consume drugs for a period of at least 2 years prior to the analysis. Statistically significant differences were found between alcoholics and controls in the frequency of SCEs/cell (P = 0.001), RI value (P = 0.001), CAs (P = 0.002) and CAB (P = 0.002). Vice versa, no significant differences were found between alcoholics and controls in terms of MNs frequency and CBPI value. In both samples, no statistically significant association was found between the analysed GSTs gene polymorphisms and the frequencies of MNs, SCEs and CAs. Finally, among alcoholics we found a positive correlation between SCEs and CAs frequencies and the duration of alcohol abuse.

Association between HTR7 genetic polymorphisms and alcohol dependence, using the alcohol use disorders identification test (AUDIT).

A recent genome-wide association study has identified 5-hydroxytrytamine (serotonin) receptor 7, adenylate cyclase-coupled (HTR7) as a risk gene for alcohol dependence. In addition, the serotonergic system has been considered as a modulator that plays an important role in alcohol use disorders. Functional, pharmacological, and genetic studies of serotonin neurotransmission have revealed that serotonin receptors are potential targets for the treatment of alcohol use disorders. The aim of this study is to investigate whether associations between HTR7 genetic polymorphisms and alcohol dependence could be replicated. This study genotyped a total of 22 common single nucleotide polymorphisms (SNPs) in 459 alcoholic patients and 444 nonalcoholic controls. Logistic regression analysis of the case-control study, controlling for age and sex as covariates, showed nominal associations of 7 SNPs (p = 0.02 to 0.04; odds ratio = 0.60 to 1.35). In further linear regression analysis based on the Alcohol Use Disorders Identification Test score for alcohol dependence, 8 SNPs and 3 haplotypes showed relatively significant associations with alcohol dependence (minimum p = 0.001; p(corr) = 0.02). Although further replications and functional evaluations are needed, our findings suggest that genetic variations of HTR7 may contribute to the predisposition for alcohol dependence.

Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics

BackgroundThe liver is the first line of defence against continuously occurring influx of microbial-derived products and bacteria from the gut. Intestinal bacteria have been implicated in the pathogenesis of alcoholic liver cirrhosis. Escape of intestinal bacteria into the ascites is involved in the pathogenesis of spontaneous bacterial peritonitis, which is a common complication of liver cirrhosis. The association between faecal bacterial populations and alcoholic liver cirrhosis has not been resolved.MethodsRelative ratios of major commensal bacterial communities (Bacteroides spp., Bifidobacterium spp., Clostridium leptum group, Enterobactericaea and Lactobacillus spp.) were determined in faecal samples from post mortem examinations performed on 42 males, including cirrhotic alcoholics (n = 13), non-cirrhotic alcoholics (n = 15), non-alcoholic controls (n = 14) and in 7 healthy male volunteers using real-time quantitative PCR (RT-qPCR). Translocation of bacteria into liver in the autopsy cases and into the ascites of 12 volunteers with liver cirrhosis was also studied with RT-qPCR. CD14 immunostaining was performed for the autopsy liver samples.ResultsRelative ratios of faecal bacteria in autopsy controls were comparable to those of healthy volunteers. Cirrhotics had in median 27 times more bacterial DNA of Enterobactericaea in faeces compared to the healthy volunteers (p = 0.011). Enterobactericaea were also the most common bacteria translocated into cirrhotic liver, although there were no statistically significant differences between the study groups. Of the ascites samples from the volunteers with liver cirrhosis, 50% contained bacterial DNA from Enterobactericaea, Clostridium leptum group or Lactobacillus spp.. The total bacterial DNA in autopsy liver was associated with the percentage of CD14 expression (p = 0.045). CD14 expression percentage in cirrhotics was significantly higher than in the autopsy controls (p = 0.004).ConclusionsOur results suggest that translocation of intestinal bacteria into liver may be involved as a one factor in the pathogenesis of alcoholic liver cirrhosis.

Risk of Depressive Disorder following Non-Alcoholic Cirrhosis: A Nationwide Population-Based Study

Background & AimsTo evaluate the risk of depressive disorders among non-alcoholic patients by using the Taiwan National Health Insurance Research Database (NHIRD).MethodsWe conducted a retrospective study of a matched cohort of 52 725 participants (10 545 non-alcoholic cirrhotic patients and 42 180 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 11 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in cirrhotic patients.ResultsDuring the 11-year follow-up period, 395 (3.75%) non-alcoholic cirrhotic patients and 1 183 (2.80%) control patients were diagnosed with depressive disorders. The incidence risk ratio of depressive disorders between non-alcoholic cirrhotic patients and control patients was 1.76 (95% CI, 1.57–1.98, P<.001). After adjusting for age, sex, and comorbidities, non-alcoholic cirrhotic patients were 1.75 times more likely to develop depressive disorders (95% CI, 1.56–1.96, P<.001) compared with the control patients. The hazard ratios for patients younger than 60 years old (1.31) and female (1.25) indicated that each is an independent risk factor for depressive disorders in non-alcoholic cirrhotic patients.ConclusionsThe likelihood of developing depressive disorders is greater among non-alcoholic cirrhotic patients than among patients without cirrhosis. Symptoms of depression should be sought in patients with cirrhosis.

Give me just a little more time: Effects of alcohol on the failure and recovery of cognitive control.

Numerous externalizing behaviors, from aggression to risk taking to drug abuse, stem from impaired cognitive control, including that brought about by the acute effects of alcohol. Although research generally indicates that alcohol impairs cognitive abilities, a close examination of the literature suggests that alcohol's effects are quite variable and likely depend on a number of contextual factors. The purpose of the current study was to characterize the effects of alcohol on cognitive control in terms of neural and behavioral responses to successful and unsuccessful control attempts. Participants were randomly assigned to consume an alcohol (0.80 g/kg ETOH), placebo, or nonalcoholic control beverage prior to completing a cognitive control (flanker) task while event-related brain potentials were recorded. Alcohol reduced the amplitude of the error-related negativity on error trials and increased the posterror compatibility effect in response time. Of particular interest, neural indices of conflict monitoring and performance adjustment (frontal slow wave) were attenuated by alcohol, but only on trials following errors. These functions had recovered, however, by 2 trials after an error. These findings suggest that alcohol's effects on cognitive control are best characterized as impaired (or delayed) recovery following control failures. Implications of these findings for understanding alcohol's effects on behavioral undercontrol are discussed.

Effect of Alcohol Consumption on Platelet, Prothrombin Time and Activated Partial Thromboplastin Time of Alcoholics in Birnin Kebbi, Kebbi State, Nigeria

Aims: Alcoholism is a global public health problem with significant socioeconomic implications. The aim was to investigate the effect of alcoholism on the haematological Original Research Article International Journal of TROPICAL DISEASE & Health, 4(2): 224-232, 2014 225 and haemostatic parameters of consecutively recruited alcoholics in Birnin Kebbi, Kebbi State and North Western Nigeria. Study Design and Methodology: This prospective case-control study included one hundred adults alcoholics [≥18 years), aged range (18-60), mean age (38.46 ± 13.26) and made up of 68 males (68%) and 32 females (32%)]. Fifty gender and age matched nonalcoholics were monitored as controls. Ethical approval was obtained from the research and ethics committee in the Faculty of Medical Laboratory Science of the Usmanu Danfodiyo University Sokoto, North Western Nigeria. Written informed consent was obtained from all study subjects after counselling. Place and Duration of Study: This study was carried out at the service laboratory in the Department of Haematology, Faculty of Medical Laboratory Science in Usmanu Danfodiyo University in Sokoto North Western Nigeria between May 2011 to February, 2012. Result: Participants for this study included 50 heavy alcoholics and 50 moderate alcoholics (subjects) and 50 age and gender –matched non-alcoholics (controls). Platelet count of non-alcoholics, moderate and heavy alcoholics was; 260.7 ± 48.17, 253.3 ± 43.16 and 130.6 ± 6.79 respectively. Platelet count was significantly lower among heavy alcoholics compared to non-alcoholics (p=0.0001). Although marginally higher, there was no statistically significant difference in the platelet count of moderate alcoholics and nonalcoholics (p=0.10). We observed a negative correlation between platelet count and duration of alcoholism (r=-0.62). The mean prothrombin time (PT) and activated partial thromboplastin time (APTT) values of non-alcoholics, moderate alcoholics and heavy alcoholics was; (14.46 ± 0.97 and 34.82 ± 13.71), (15.74 ± 1.26 and 35.78 ± 3.50) and (19.46 ± 0.93 and 43.42 ± 5.13) respectively. Prothrombin time and activated partial thromboplastin time values were significantly lower among heavy alcoholics compared to non-alcoholics (p=0.0001). PT and APTT were marginally higher among moderate alcoholics compared to non-alcoholics but the difference however was not statistically significant (p= 0.08 and 0.62 respectively). We observed a positive correlation between duration of alcoholism and prolonged prothrombin time and activated partial thromboplastin time (r = 0.46 and 0.55 respectively). Conclusion: Our study has shown that alcoholism produces a significant adverse effect on some haematological and haemostatic parameters. Evidenced data generated from this study can facilitate the development of a policy on the effective management of haematological and haemostatic complications associated with alcoholism. There is need to enact laws that regulate the production, sales and consumption of various alcoholic beverages to prevent abuse and protect the health of citizens.

Irisin in patients with nonalcoholic fatty liver disease

ObjectiveIrisin is a recently discovered myokine proposed to increase thermogenesis-related energy expenditure and improve metabolism. We aimed to comparatively evaluate serum irisin levels in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) vs. controls and study their association with disease severity. MethodsFifteen and 16 consecutively enrolled patients with biopsy-proven nonalcoholic simple steatosis (NAFL) and steatohepatitis (NASH), respectively, and 24 lean and 28 obese controls without NAFLD were recruited. Irisin, established adipokines and biochemical tests were measured. ResultsSerum irisin levels were statistically different in obese controls (33.7±2.7ng/mL; p<0.001) and patients with NAFL (30.5±1.5ng/mL; p<0.001) and NASH (35.8±1.9ng/mL; p=0.001) compared with lean controls (47.7±2.0ng/mL), but were similar among patients with NAFL, NASH and obese controls. This difference remained significant after adjustment for body mass index (or waist circumference), gender, age, insulin resistance (assessed by HOMA-IR or QUICKI), exercise and time since blood collection. Serum leptin and adiponectin, but not irisin, levels were independently from BMI correlated with insulin resistance and cardiometabolic factors. Serum irisin tended to be higher in patients with (36.7±2.4ng/mL) than without (30.8±1.2ng/mL; p=0.02) portal inflammation and independently associated with the latter; these data need to be confirmed by future studies. ConclusionsSerum irisin levels differ between lean controls and obese controls or NAFLD patients. Despite similar circulating irisin levels between NAFL and NASH groups, irisin may be independently and positively associated with the presence of portal inflammation. Future clinical and mechanistic studies are needed to confirm and extend these data.

Characteristics of Heart Rate Variability in Alcohol-Dependent Subjects and Nondependent Chronic Alcohol Users

Heart rate variability (HRV) is an objective and sensitive measure of integrated physiological functioning reflective of heart rhythm responsivity to internal and external demands. Reduced HRV is associated with vulnerability to stress and deterioration of medical and/or psychiatric conditions, while increased HRV is associated with a favorable treatment response and recovery from various medical and/or psychiatric conditions. Our previous review found that acute alcohol consumption caused decreased parasympathetic and increased sympathetic HRV effects in both nonalcoholic and chronic alcohol users. This review investigates the effects of chronic alcohol consumption on HRV in alcohol-dependent subjects and nondependent users. MEDLINE, Scopus, and PubMed were searched for human experimental and clinical trials that measured the effects of chronic alcohol use on HRV. Only publications that included a description of their study designs and clearly stated methodologies for data collections, and outcome measures were reviewed. We have reviewed a total of 24 articles. In nondependent users, low dose (approximating the recommended daily amount of 1 standard drink in women and 2 in men) use is associated with increased HRV parameters compared to those who drink less frequently or abstain altogether. A further increase in consumption is associated with decreased HRV compared to both abstainers and more moderate drinkers. HRV changes during withdrawal generally follow the same negative direction but are more complex and less understood. In dependent subjects, an improvement in HRV was seen following abstinence but remained reduced compared to nonalcoholic controls. This review demonstrates that HRV changes associated with chronic use follow a J-shaped curve. It supports recommendations that limit daily alcohol intake to no more than 2 drinks for men and 1 drink for women. Future studies should investigate HRV as a biomarker of alcoholism development and treatment response as well as the physiological basis for alcohol effects on HRV.

AMPA receptors in post-mortem brains of Cloninger type 1 and 2 alcoholics: A whole-hemisphere autoradiography study

Dysfunction of the brain glutamate system has been associated with alcoholism. Ionotropic glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) play an important role in both neurotransmission and post-synaptic plasticity. Alterations in AMPAR densities may also play a role in the neurobiological changes associated with alcoholism. In the present study, [3H] AMPA binding density was evaluated in the nucleus accumbens (NAc), frontal cortex, anterior cingulate cortex (ACC), dentate gyrus and hippocampus of Cloninger type 1 (n=9) and 2 (n=8) alcoholics, and compared with non-alcoholic control subjects (n=10) by post-mortem whole-hemisphere autoradiography. The [3H] AMPA binding density was significantly higher in the ACC of early onset type 2 alcoholics when compared with controls (p=0.011). There was also a significant negative correlation between [3H] AMPA binding and previously published results of dopamine transporter (DAT) density in the ACC in these same brain samples (R=−0.95, p=0.001). Although preliminary, and from a relatively small diagnostic group, the present results help to further explain the pathology of alcohol dependence and impulsive behaviour in type 2 alcoholics.

The Relationship between Intestinal Motility and Interstitial Cells of Cajal in Nonalcoholic Fatty Liver Mice

BackgroundNonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in western world. However, NAFLD shows an increasing trend in China every year, which has attracted the attention of national health authorities. The previous studies have shown that NAFLD caused severe gastrointestinal motor disorders, but little is known about the interstitial cells of Cajal (ICC) role in gastrointestinal motor disorders.ObjectivesThe aim of this study was to observe the ICC in jejunum of nonalcoholic fatty liver mice by immunohistochemistry and assessed the relationship between intestinal motility and ICC.Materials and MethodsThirty five Sprague-Dawley (SD) rats were randomly divided into nonalcoholic fatty liver (n = 25) and control groups (n = 10), rats were housed individually in cages and had free access to food and water, nonalcoholic fatty liver group was duplicated by high-fat diet (consisted of ordinary food, 20 g/kg cholesterol and 100 g/kg fat) feeding. Dextran blue-2000 was used to monitor the intestinal motility. The proximal small intestine was harvested to investigate the C-kit positive ICC. The hepatic tissue slices were used for pathological observation.ResultsNonalcoholic fatty liver disease was successfully established. The intestinal motility in nonalcoholic fatty liver group (49.5 ± 10.9) was weaker compared to the control group (57.3 ± 8.9), P < 0.05. The rate of ICC also have shown statistically significant differences between nonalcoholic fatty liver (4.87 ± 2.97/mm 2) and control groups (6.54 ± 3.13/mm 2), P < 0.05.ConclusionsICC may be related to the intestinal motility in nonalcoholic fatty liver mice.

Variants in CPA1 are strongly associated with early onset chronic pancreatitis

Chronic pancreatitis is an inflammatory disorder of the pancreas. We analyzed CPA1, encoding carboxypeptidase A1, in subjects with nonalcoholic chronic pancreatitis (cases) and controls in a German discovery set and three replication sets. Functionally impaired variants were present in 29/944 (3.1%) German cases and 5/3,938 (0.1%) controls (odds ratio (OR) = 24.9, P = 1.5 × 10(-16)). The association was strongest in subjects aged ≤ 10 years (9.7%; OR = 84.0, P = 4.1 × 10(-24)). In the replication sets, defective CPA1 variants were present in 8/600 (1.3%) cases and 9/2,432 (0.4%) controls from Europe (P = 0.01), 5/230 (2.2%) cases and 0/264 controls from India (P = 0.02) and 5/247 (2.0%) cases and 0/341 controls from Japan (P = 0.013). The mechanism by which CPA1 variants confer increased pancreatitis risk may involve misfolding-induced endoplasmic reticulum stress rather than elevated trypsin activity, as is seen with other genetic risk factors for this disease.

Endogenous cannabinoids in amygdala and hippocampus in post-mortem brains of Cloninger type 1 and 2 alcoholics

Accumulating evidence continues to link certain aspects of the endogenous cannabinoid (EC) system with alcohol dependence, negative-reinforcement learning, and the modulation of stress responses. Specific alterations in brain regions that are related to stress and negative-reinforcement learning have been reported to exist in Cloninger type 1 and type 2 alcoholics. To study possible differences in profiles of EC systems between Cloninger type 1 (n = 9) and type 2 (n = 8) alcoholics and non-alcoholic control subjects (n = 10), we analyzed post-mortem amygdala and hippocampus brain samples for several ECs by quantitative liquid chromatography with triple quadrupole mass-spectrometric detection. A significant difference was found between these 3 groups in terms of EC profiles in the amygdala (p = 0.037). In particular, this difference was prominent for variations in docosahexaenoylethanolamide levels, which were significantly higher in type 1 alcoholics (p = 0.022) when compared to controls. There was also a large negative correlation between anandamide concentration and mGlu1/5 receptor density in the hippocampi of Cloninger type 1 alcoholics (R = −0.88, p = 0.002), which was not seen in Cloninger type 2 alcoholics or in controls. Although preliminary, and from relatively small diagnostic groups, these results suggest that the EC system profile may be altered in the hippocampus and amygdala of Cloninger type 1 alcoholics.

Study on dermatoses and their prevalence in groups of confirmed alcoholic individuals in comparison to a non-alcoholic group of individuals

BACKGROUND The direct relationship between alcoholism and dermatoses has been evaluated in recent researches. However, there are few objective surveys that demonstrate and prove a direct relationship between alcohol and a specific dermatosis. OBJECTIVES to verify the prevalence of dermatoses in alcoholics, analize the dermatological changes found in these patients and their evolution during alcoholic abstinence. Also, to compare the results obtained with a non-alcoholic control group and with the data found in medical literature. METHODS: the dermatologic conditions of 278 alcoholic patients (250 men, 28 women) were studied over a period of 4 years, and compared to those of a control group of 271 non-alcoholic individuals (249 men, 22 women), members of the Military Police Force. The individuals in both groups were between 20 and 60 years old. RESULTS Pellagra, nummular eczema, purpura pigmentosa chronica (also known as pigmented purpuric dermatosis) and psoriasis were more frequent in the group of alcoholics and, apparently, occurred in parallel with alcoholism that seems to play a role in the evolution of these dermatoses. The dermatopathies were more frequent before the age of forty, regardless of factors such as profession, race or gender. CONCLUSION the association of dermatoses and alcoholism was extremely significant according to the statistical data. Alcoholism can be considered a risk factor for pellagra, psoriasis, nummular eczema and purpura pigmentosa chronica dermatoses, which can, as well, be considered alcoholism indicators.

Replication of Genome Wide Association Studies of Alcohol Dependence: Support for Association with Variation in ADH1C

Genome-wide association studies (GWAS) have revealed many single nucleotide polymorphisms (SNPs) associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017). Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI) = 0.80 (0.66, 0.95); women: OR (95%CI) = 0.83 (0.66, 1.03)). We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081), and independently in the alcohol-dependent cases (p = 0.046). Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.

Implicit and Explicit Attitudes to Alcohol in Alcohol Dependent and Non-Alcohol Dependent Samples

Measures of implicit and explicit attitudes to alcohol have been used to predict drinking behavior. Early studies with the bipolar Implicit Association Test (IAT) indicated that heavy drinkers hold negative implicit attitudes to alcohol. More recent studies using the unipolar IAT have found that positive implicit attitudes to alcohol are associated with drinking behavior in samples of university students. The present study is the first to use a unipolar single target IAT to assess positive alcohol-related attitudes in two samples with alcohol dependency compared to a non-alcohol dependent control group. A group of recently detoxed alcohol dependent adults entering a treatment program (n = 22), a group of alcohol dependent adults who had been in treatment for 3 months (n = 22), and a group of age matched adults who had no history of alcohol dependence (n = 22) were compared on a positive unipolar single target IAT and an explicit attitude measure. Results indicated that alcohol dependent participants showed stronger positive implicit attitudes, and stronger negative explicit associations compared to non-alcohol dependent participants, but there were no differences between the two groups with alcohol dependency. The findings are discussed in terms of the role of the IAT as an assessment tool for those undertaking treatment for alcohol problems and the implications for targeting unconscious attitudes to alcohol in a clinical setting.

Genetic signatures in choline and 1‐carbon metabolism are associated with the severity of hepatic steatosis

Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleotide polymorphisms (SNPs) across genes of choline/1-carbon metabolism and functionally related pathways increase susceptibility to developing hepatic steatosis. In biopsy-characterized cases of nonalcoholic fatty liver disease and controls, we assessed 260 SNPs across 21 genes in choline/1-carbon metabolism. When SNPs were examined individually, using logistic regression, we only identified a single SNP (PNPLA3 rs738409) that was significantly associated with severity of hepatic steatosis after adjusting for confounders and multiple comparisons (P=0.02). However, when groupings of SNPs in similar metabolic pathways were defined using unsupervised hierarchical clustering, we identified groups of subjects with shared SNP signatures that were significantly correlated with steatosis burden (P=0.0002). The lowest and highest steatosis clusters could also be differentiated by ethnicity. However, unique SNP patterns defined steatosis burden irrespective of ethnicity. Our results suggest that analysis of SNP patterns in genes of choline/1-carbon metabolism may be useful for prediction of severity of steatosis in specific subsets of people, and the metabolic inefficiencies caused by these SNPs should be examined further.

Induced Theta Activity as a Biomarker for a Morbid Effect of Alcoholism on the Brain in Long-Term Abstinent Alcoholics

Event-related, target stimulus-phase-locked (evoked) brain activity in both the time and time-frequency (TF) domains (the P3b ERP; evoked theta oscillations) has been shown to be reduced in alcoholics. Recently, studies have suggested that there is alcohol-related information in the non-stimulus-phase-locked (induced) theta TF activity. We applied TF analysis to target stimulus event-related EEG recorded during an oddball task from 41 long-term abstinent alcoholics (LTAA) and 74 nonalcoholic controls (NAC) to investigate the relationship between P3b, evoked theta, and induced theta activity. Results showed that an event-related synchronization (ERS) of induced theta (1) was larger in LTAA compared to NAC, and (2) was sensitive to differences between LTAA and NAC groups that was independent of the differences accounted for by P3b amplitude or evoked theta. These findings suggest that increased induced theta ERS may likely be a biomarker for a morbid effect of alcohol abuse on brain function.

1344 – PDYN rs2281285 variant is associated with alcohol dependence in male but not female subjects

Recent findings support sex-specific effects of PDYN polymorphisms on association with opioid addiction (Clarke et al. 2012). We have demonstrated that PDYN haplotypes, which include rs2281285, are associated with alcohol dependence and propensity to drink in negative emotional situations (negative craving) (Karpyak et al 2012). The rs2281285 variant may contribute to regulation of alternative PDYN mRNA transcription specific to brain area or physiological condition. To investigate sex-specific effects of the PDYN rs2281285 variant on risk for alcohol dependence. To examine the association of the PDYN rs2281285 variant with alcohol dependence in male and female subjects. rs2281285 was genotyped in the investigation cohort of 816 (554 males) alcohol dependent subjects (DSM-IV-TR) and 1248 (603 males) non-alcoholic controls and in the replication cohort of 467 (347 males) alcohol dependent subjects and 431 (224 males) non-alcoholic controls. Logistic regression models were used to test for sex-specific associations after controlling for age. As previously reported, significant association of the PDYN rs2281285 variant with alcohol dependence was found in the investigation (p = 0.008, odds ratio = 1.299), but not the replication cohort (0.223, OR = 0.118). However, sex-specific analyses revealed stronger association in males (p = 0.002, OR = 1.493) but not females (p = 0.684, OR = 1.066) in the investigation cohort, and a trend for association in males (p = 0.086, OR = 1.352) but not females (p = 0.808, OR = 0.947) in the replication cohort. Our findings support association of PDYN rs2281285 variant with alcohol dependence in male but not female subjects. Future studies should investigate functional mechanisms of this effect.