Risk For Alcohol Use Disorder Research Articles

Binge and high-intensity drinking-Associations with intravenous alcohol self-administration and underlying risk factors.

Some styles of alcohol consumption are riskier than others. How the level and rate of alcohol exposure contribute to the increased risk of alcohol use disorder is unclear, but likely depends on the alcohol concentration time course. We hypothesized that the brain is sensitive to the alcohol concentration rate of change and that people at greater risk would self-administer faster. We developed a novel intravenous alcohol self-administration paradigm to allow participants direct and reproducible control over how quickly their breath alcohol concentration changes. We used drinking intensity and the density of biological family history of alcohol dependence as proxies for risk. Thirty-five alcohol drinking participants aged 21-28 years provided analytical data from a single, intravenous alcohol self-administration session using our computer-assisted alcohol infusion system rate control paradigm. A shorter time to reach 80 mg/dl was associated with increasing multiples of the binge drinking definition (p = 0.004), which was in turn related to higher density of family history of alcoholism (FHD, p = 0.04). Rate-dependent changes in subjective response (intoxication and stimulation) were also associated with FHD (each p = 0.001). Subsequently, given the limited sample size and FHD range, associations between multiples of the binge drinking definition and FHD were replicated and extended in analyses of the Collaborative Study on the Genetics of Alcoholism database. The rate control paradigm models binge and high-intensity drinking in the laboratory and provides a novel way to examine the relationship between the pharmacokinetics and pharmacodynamics of alcohol and potentially the risk for the development of alcohol use disorders.

Statistical Validation of Risk Alleles in Genetic Addiction Risk Severity (GARS) Test: Early Identification of Risk for Alcohol Use Disorder (AUD) in 74,566 Case-Control Subjects.

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), Blum’s group developed the Genetic Addiction Risk Severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions published from 1990 until 2021. This analysis calculated the Hardy–Weinberg Equilibrium of each polymorphism in cases and controls. If available, the Pearson’s χ2 test or Fisher’s exact test was applied to comparisons of the gender, genotype, and allele distribution. The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population’s alcoholism prevalence revealed a significant detection. The OR results showed significance for DRD2, DRD3, DRD4, DAT1, COMT, OPRM1, and 5HTT at 5%. While most of the research related to GARS is derived from our laboratory, we are encouraging more independent research to confirm our findings.

Trauma Cue-Elicited Alcohol Craving as a Function of Adult Versus Childhood-Onset Interpersonal Traumatic Events in Young Adult Drinkers.

Childhood trauma may influence risk for alcohol use disorder and posttraumatic stress disorder through negative and positive reinforcement drinking. Laboratory studies evaluating childhood trauma in relation to these phenotypes are limited. This study examined the influence of childhood index traumas on responses to trauma and alcohol cues among 184 college students (50.0% female) endorsing lifetime interpersonal trauma and current weekly alcohol use. Participants' subjective alcohol craving and distress were measured in response to four narrative (trauma vs. neutral) and beverage (alcohol vs. water) cue combinations. Forward-fitted linear mixed-effects models indicated main effects of childhood index traumas on distress (β= 6.151, p = .001) and craving (β = 0.656, p = .023), wherein individuals with childhood index traumas showed evidence of elevated levels of distress and craving. Childhood index trauma interacted with the narrative cue to predict distress (β = -10.764, p = .002), wherein individuals with childhood index traumas showed greater levels of distress to the neutral cue, and individuals with adult index traumas showed greater levels of distress to the trauma cue. Childhood index trauma interacted with the beverage cue to predict craving (β = -0.599, p = .011), wherein childhood index traumas were associated with greater levels of craving to neutral cues. Childhood index trauma did not significantly interact with the beverage cue to predict distress or the narrative cue to predict craving (ps > .05). Childhood trauma may be more relevant to positive rather than negative reinforcement aspects of alcohol use disorder during young adulthood.

Cross-generational transmission of genetic risk for alcohol and drug use disorders: the impact of substance availability on the specificity of genetic risk.

Among individuals with alcohol use disorder (AUD) and drug use disorder (DUD), is their genetic liability and its specificity moderated by substance availability? Offspring (born 1960-1995) and their biological parents from three family types [not-lived-with (NLW) biological father, mother and adoptive] and their AUD and DUD diagnoses were ascertained from Swedish national registers. Parent-offspring resemblance was calculated by tetrachoric correlation. In Swedes born from 1960 to 1995, prevalence rates of AUD were stable while DUD rates increased substantially. Best-estimate tetrachoric correlations (±95% confidence intervals) between AUD in biological parents and AUD and DUD in their offspring were, respectively, +0.19 (0.18-0.20) and +0.18 (0.17-0.20). Parallel results from DUD in parents to AUD and DUD in children were +0.12 (0.10-0.13) and +0.27 (0.26-0.28). When divided into older and younger cohorts, the specificity of DUD transmission increased substantially over time, while the genetic correlation between AUD and DUD significantly decreased. Raised when alcohol was the preferred substance of abuse and illicit drugs highly stigmatized, AUD in parents reflected a general liability to substance use disorders, as they transmitted similar genetic risk for AUD and DUD to their children raised when both substances were widely available and relatively acceptable. DUD in parents, by contrast, reflected a more specific liability to DUD and, when transmitted to offspring, produced a considerably stronger risk for DUD than for AUD that increased over time. The magnitude and specificity of the genetic liability to psychoactive substances can be influenced by the availability of that substance.

Developmental genetic effects on externalizing behavior and alcohol use: Examination across two longitudinal samples.

Externalizing behavior in early adolescence is associated with alcohol use in adolescence and early adulthood and these behaviors often emerge as part of a developmental sequence. This pattern can be the result of heterotypic continuity, in which different behaviors emerge over time based on an underlying shared etiology. In particular, there is largely a shared genetic etiology underlying externalizing and substance use behaviors. We examined whether polygenic risk for alcohol use disorder predicted (1) externalizing behavior in early adolescence and alcohol use in adolescence in the Early Steps Multisite sample and (2) externalizing behavior in adolescence and alcohol use in early adulthood in the Project Alliance 1 (PAL1) sample. We examined associations separately for African Americans and European Americans. When examining European Americans in the Early Steps sample, greater polygenic risk was associated with externalizing behavior in early adolescence. In European Americans in PAL1, we found greater polygenic risk was associated with alcohol use in early adulthood. Effects were largely absent in African Americans in both samples. Results imply that genetic predisposition for alcohol use disorder may increase risk for externalizing and alcohol use as these behaviors emerge developmentally.

The role of adolescent social relationships in promoting alcohol resistance: Interrupting the intergenerational transmission of alcohol misuse.

Genetic factors contribute to the intergenerational transmission of alcohol misuse, but not all individuals at high genetic risk develop problems. The present study examined adolescent relationships with parents, peers, and romantic partners as predictors of realized resistance, defined as high biological risk for disorder combined with a healthy outcome, to alcohol initiation, heavy episodic drinking, and alcohol use disorder (AUD). Data were from the Collaborative Study on the Genetics of Alcoholism (N = 1,858; 49.9% female; mean age at baseline = 13.91 years). Genetic risk, indexed using family history density and polygenic risk scores for alcohol problems and AUD, was used to define alcohol resistance. Adolescent predictors included parent-child relationship quality, parental monitoring, peer drinking, romantic partner drinking, and social competence. There was little support for the hypothesis that social relationship factors would promote alcohol resistance, with the exception that higher father-child relationship quality was associated with higher resistance to alcohol initiation ( , 95% CI = -0.35, -0.03). Unexpectedly, social competence was associated with lower resistance to heavy episodic drinking ( , 95% CI = 0.01, 0.20). This pattern of largely null effects underscores how little is known about resistance processes among those at high genetic risk for AUD.

Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats.

With the substantial social and medical burden of addiction, there is considerable interest in understanding risk factors that increase the development of addiction. A key feature of alcohol use disorder (AUD) is compulsive alcohol (EtOH) drinking, where EtOH drinking becomes “inflexible” after chronic intake, and animals, such as humans with AUD, continue drinking despite aversive consequences. Further, since there is a heritable component to AUD risk, some work has focused on genetically-selected, EtOH-preferring rodents, which could help uncover critical mechanisms driving pathological intake. In this regard, aversion-resistant drinking (ARD) takes >1 month to develop in outbred Wistar rats (and perhaps Sardinian-P EtOH-preferring rats). However, ARD has received limited study in Indiana P-rats, which were selected for high EtOH preference and exhibit factors that could parallel human AUD (including front-loading and impulsivity). Here, we show that P-rats rapidly developed compulsion-like responses for EtOH; 0.4 g/L quinine in EtOH significantly reduced female and male intake on the first day of exposure but had no effect after one week of EtOH drinking (15% EtOH, 24 h free-choice paradigm). Further, after 4–5 weeks of EtOH drinking, males but not females showed resistance to even higher quinine (0.5 g/L). Thus, P-rats rapidly developed ARD for EtOH, but only males developed even stronger ARD with further intake. Finally, rats strongly reduced intake of quinine-adulterated water after 1 or 5 weeks of EtOH drinking, suggesting no changes in basic quinine sensitivity. Thus, modeling ARD in P-rats may provide insight into mechanisms underlying genetic predispositions for compulsive drinking and lead to new treatments for AUDs.

Alcohol use disorder among Whites and Hispanics on and off the U.S./Mexico border in California

This paper examines whether U.S./Mexico border residence in California is related to the prevalence of DSM-5 alcohol use disorder (AUD) among Whites and Hispanics. Household survey data were obtained from 1,209 adults (59.7% female) 18 to 39 years of age resident in four counties in California: Imperial on the U.S./Mexico border; and Kern, Tulare, and Madera in California’s Central Valley. Households were selected using a list assisted sample, with data collected on the phone or online. Results show that AUD rates were not different between border and non-border location and between Whites and Hispanics. AUD was negatively associated with higher income ($20,000 to $60,000: AOR=.38; 95%CI=.17–.86; p<.01—more than $60,000: AOR=.27; 95%CI: .09–.81; p<.01) and poor risk perception (AOR=.86; 95%CI=.78–.94; p<.01). AUD was positively associated with continued volume of drinking (AOR = 1.05; 95%CI = 1.01–1.09; p<.01), drinking in Mexico (AOR = 4.28; 95%CI = 1.61–11.36; p<.01), marijuana use (AOR = 4.11; 95%CI = 1.73–9.77; p<.01), and impulsivity (AOR = 1.55; 95%CI = 1.23–1.94). Efforts to prevent AUD in the population in California, and especially among those who live close to the border with Mexico, should take into consideration factors such as impulsivity, marijuana use, border crossing to drink in Mexico, all of which increased risk of AUD.

Social Determinants of Alcohol Use Disorder, Depression, and Anxiety Among Sexual Minority Males During the COVID-19 Pandemic

he COVID-19 pandemic magnified the mental health disparities between sexual minorities and the Filipino population. This study explored the mental health disparities experienced by sexual minorities, which remains unexplored. The study utilized self-administered survey forms to explore the extent and social determinants of an alcohol use disorder, depression, and anxiety among Filipino sexual minority males during the pandemic. A total of 220 participants were recruited in October 2020. They were composed of adult Filipino cisgender males with non-heterosexual orientation from Metro Manila. The results showed significant rates of risk for alcohol use disorder, depression, and anxiety at 36.4%, 9.5%, and 26.4%, respectively. Age (OR=0.886, p=.025), homosexual orientation (OR=0.035, p=.033), bisexual orientation (OR= 0.009, p=.011), and living with relatives (OR=0.162, p=.006) were also significantly associated with depression. Age (OR=0.866, p=&lt;.001) was significantly associated with anxiety. Moreover, compared with the general population during the pandemic, Filipino sexual minorities’ risk for alcohol use disorder was higher than depression and anxiety. These disparities were significantly associated with age, sexual orientation, and living arrangements. The findings suggest comorbidities of an alcohol use disorder, depression, and anxiety among Filipino sexual minorities that can be addressed through cost-effective online treatment modalities, information-education campaigns, integration of mental health into educational curriculums, the institution of policies that bar discrimination against sexual minorities, and initiatives to strengthen family support groups.

Pharmacodynamic determinants of hangover: An intravenous alcohol self-administration study in non-dependent drinkers

Alcohol hangover refers to the combination of negative mental and physical symptoms that can be experienced after an episode of alcohol consumption, typically emerging as blood alcohol concentration (BAC) approaches zero. Hangover has been associated with heavy drinking and may be relevant in the transition to alcohol use disorder (AUD). Our aim was to examine hangover prevalence and associated symptoms following intravenous alcohol self-administration (IV-ASA), and to identify possible predictors of hangover in non-dependent drinkers.Ninety-five drinkers without AUD completed an IV-ASA session. Pharmacodynamic measures of alcohol consumption included peak and average breath alcohol concentrations. Subjective measures of alcohol response included the Drug Effects Questionnaire and Biphasic Effects of Alcohol Scale. The Alcohol Hangover Scale assessed hangover symptoms from the end of the session until the following morning.78% of participants endorsed at least one hangover symptom following IV-ASA. There was no association between hangover scores and IV-ASA measures of alcohol consumption. Additional mediation and moderation analysis revealed that self-reported intoxication was a significant mediator of the relationship between recent drinking and hangover symptoms.Hangover symptoms may be an early marker of the relationship between subjective response to alcohol and heavy drinking for those with no prior history of AUD. In particular, the effects of hangover go beyond exposure to alcohol and the individual’s subjective response to this exposure is associated with their experience of hangover. Future studies should further characterize the determinants of hangover across different populations of drinkers to better understand the risk for AUD and inform prevention methods.

Predicting severe alcohol use disorders in primary care using number of heavy drinking days.

Although screening for unhealthy alcohol use is becoming more common, severe alcohol use disorders (AUDs) associated with the most severe medical and socio-economic sequelae still often go unidentified in primary care. To improve identification of severe AUDs and aid clinical decision-making, we aimed to identify a threshold of heavy drinking days (HDDs) associated with severe AUDs. This cohort study analyzed electronic health record data of 138 765 adults who reported ≥ 1 HDD (4+ drinks/occasion for women and men aged ≥ 65 years, 5+ for men aged 18-64 years) during a 3-month period at a routine alcohol screening in primary care in a large Northern California, USA health-care system from 2014 to 2017. Our sample was 66.5% male, 59.7% white, 11.0% Asian/Pacific Islander, 5.0% black, 17.4% Latino/Hispanic and 7.0% other/unknown race/ethnicity; the mean age was 40.6years (standard deviation = 15.2). We compared sensitivity and specificity of different thresholds of the reported number of HDDs during a 3-month period for predicting severe AUD diagnoses in the following year, in the full sample and by sex and age. The prevalence of severe AUD diagnoses in the year after the screening was 0.6%. The optimal threshold predicting future severe AUD diagnoses in the full sample was ≥ 5 HDDs during a 3-month period [sensitivity = 68.9%, 95% confidence interval (CI) = 65.9, 72.0; specificity = 63.2%, 95% CI = 62.9, 63.4], but varied by sex and age. Women had a lower threshold than men (4 versus 6 HDDs), which decreased as women aged (from 5 HDDs among 18-24 years to 4 HDDs ≥ 25 years), but increased as men aged (from 5 HDDs among 18-24 years to 6 HDDs among 25-64 years, to 7 HDDs ≥ 65 years). Five or more heavy drinking days in a 3-month period may indicate heightened risk of future severe alcohol use disorder in an adult primary care population. The optimal thresholds are lower for women than for men, and thresholds decrease as women age but increase as men age.

A brief young adult alcohol problems screening test: Short form development using combinatorics

Objective: To develop a shortened form of the Young Adult Alcohol Problems Screening Test 1 (YAAPST; original length = 27 items) using a novel combinatorial approach. Participants: 489 college freshmen, half of whom were above average risk for alcohol use disorder based upon family history, attending a large, Midwestern University followed prospectively for 16–17 years across 7 measurement occasions (waves). Methods: Using an exhaustive combinatorial approach, we evaluated all possible combinations of questions and questionnaire length. Each candidate short-form was evaluated using part-whole correlations, alpha coefficients, and polyserial correlations with DSM-III criteria. Results: The 12-item scale, the Brief-YAAPST, was chosen as the best candidate short-form as this scale had the fewest items while maintaining strong reliability and validity. Conclusions: Complete enumeration optimization effectively produced a 12-item short form with minimal loss of reliability and validity making the Brief-YAAPST a desirable assessment alternative when there are concerns about participant or client burden.

Gene-based polygenic risk scores analysis of alcohol use disorder in African Americans

Genome-wide association studies (GWAS) in admixed populations such as African Americans (AA) have limited sample sizes, resulting in poor performance of polygenic risk scores (PRS). Based on the observations that many disease-causing genes are shared between AA and European ancestry (EA) populations, and some disease-causing variants are located within the boundaries of these genes, we proposed a novel gene-based PRS framework (PRSgene) by using variants located within disease-associated genes. Using the AA GWAS of alcohol use disorder (AUD) from the Million Veteran Program and the EA GWAS of problematic alcohol use as the discovery GWAS, we identified 858 variants from 410 genes that were AUD-related in both AA and EA. PRSgene calculated using these variants were significantly associated with AUD in three AA target datasets (P-values ranged from 7.61E−05 to 6.27E−03; Betas ranged from 0.15 to 0.21) and outperformed PRS calculated using all variants (P-values ranged from 7.28E−03 to 0.16; Betas ranged from 0.06 to 0.18). PRSgene were also associated with AUD in an EA target dataset (P-value = 0.02, Beta = 0.11). In AA, individuals in the highest PRSgene decile had an odds ratio of 1.76 (95% CI: 1.32–2.34) to develop AUD compared to those in the lowest decile. The 410 genes were enriched in 54 Gene Ontology biological processes, including ethanol oxidation and processes involving the synaptic system, which are known to be AUD-related. In addition, 26 genes were targets of drugs used to treat AUD or other diseases that might be considered for repurposing to treat AUD. Our study demonstrated that the gene-based PRS had improved performance in evaluating AUD risk in AA and provided new insight into AUD genetics.

Association of Previous Gastric Bypass Surgery and Patient Outcomes in Alcohol-Associated Cirrhosis Hospitalizations.

Roux-En-Y gastric bypass (RYGB) is associated with risk of alcohol use disorder. The impact of RYGB among patients with alcohol-associated liver disease (ALD) remains unknown. A retrospective cohort from National Inpatient Sample (01/2006-09/2015) database on 421,156 admissions with alcohol-associated cirrhosis (AC) was stratified for non-primary discharge diagnosis of previous RYGB. Admissions with RYGB (cases) were matched 1:3 to without RYGB (controls) based on propensity score on demographics, calendar year, socioeconomic status (insurance and zip code income quartile), obesity, diabetes, anxiety, and alcohol use disorder. Primary outcome was concomitant discharge diagnosis of alcoholic hepatitis (AH) or development of acute on chronic liver failure (ACLF). Of 10,168 admissions (mean age 49 yrs., 75% females, 79% whites), cases (N = 2542) vs. controls had higher prevalence of concomitant AH (18.8 vs. 17%, P = 0.032), hepatic encephalopathy (31 vs. 25%), infection (28 vs. 24%), and grade 3 ACLF (13 vs. 5%), P < 0.001. Conditional logistic regression models showed higher odds for AH, hepatic encephalopathy, and infection among cases. In-hospital mortality of 6.3% (43% in ACLF) was lower in cases, but similar in the sub-cohorts of AH (N = 1768) or ACLF (N = 768). Results were similar in a sensitivity analysis of matched cohort of 2016 hospitalizations (504 cases) with primary discharge diagnosis of AC. Among patients with AC, previous RYGB is associated with increased likelihood of concomitant AH, hepatic encephalopathy, and infection, but similar in-hospital mortality. Prospective studies are needed to validate, determine causality, and understand mechanisms of these findings among patients with alcohol-associated cirrhosis.

The actions and interactions of family genetic risk scores for alcohol use disorder and major depression on the risk for these two disorders.

We know little about how genetic risk factors for two disorders jointly act and interact in predisposing to illness. Therefore, in the Swedish population, born 1970-1990 (n=2,116,082) and followed through 2015, we examine, using additive Cox models, the impact of the family genetic risk scores (FGRS) for alcohol use disorder (AUD) and major depression (MD), their interaction with each other and with the relevant comorbid disorder on risk for AUD and MD. FGRS scores are constructed using rates of illness in first-fourth degree relatives. FGRS for AUD and MD interacted in predicting of both disorders and one FRGS (e.g., for AUD) interacted with the phenotype of MD to predict that disorder (e.g., AUD). These FGRS interactions were not substantially attenuated by adding interactions with the disorders. These results replicated across sexes. In predicting risk for a given disorder, we rarely consider genetic liabilities for other disorders. But such effects were here significant and interactive. Furthermore, the primary disorder genetic risk interacts with comorbid disorders. The pathways to risk for disorders from their and other disorders' genetic liability may be more complex than commonly considered.

알코올 사용 장애 환자들의 가족력 강도와 음주 특성

Background: It has been shown that alcohol use disorders are common within a particular family. The risk of alcohol use disorders is known to be three to five times higher for a parent than non-parent alcohol. For this reason, many studies to date have examined the family history of alcohol use problems among adolescents or early adults with drinking problems. However, most studies examined only the existence of alcohol family history, and there were no reports of familial density among alcoholics patients. Objective: The purpose of this study was to investigate the familial density of people with alcohol abuse problems and to investigate the differences in the characteristics of alcohol abuse problems according to their familial density. Method: At four community centers in Busan and Gyeongsangnam-do, familial density was investigated for clients using the service. There were 141 subjects in the study, 113 men and 28 women. Result: Of the people with alcohol use problems, familial density had four groups (family history negative, grandparents or siblings only, parent(s) only, parent(s) and grandparents or siblings, parent(s) and grandparents and siblings,). Familial density was significantly associated with frequency of violence, drinking related, AUDIT-K score. Conclusion: There is a difference in familial density among people with alcohol use problems. However, systematic comparison of variety of measures of family history is lacking. and further study is needed. This study investigated familial density in patients with alcohol use disorder. These results will be the evidence for another perspective on the genetic effects and its risks of alcohol use disorder patients.

Association between opioid therapy trajectories and potential opioid-related adverse health events.

We identified associations between membership in seven group-based trajectories based on supply of filled opioid prescriptions and potential opioid-related adverse health events over a 720-day window. We identified two veteran cohorts with chronic non-cancer pain who initiated treatment with long-term opioid therapy between 2008 and 2015, excluding those with prior substance use disorder (n=373 941) or non-SUD, opioid-related adverse outcome (n=405 631) diagnoses. Outcomes of interest included opioid use disorder, non-opioid drug use disorder, and alcohol use disorder for the first cohort; or accidents resulting in wounds or injuries, self-inflicted injuries, opioid-related accidents and overdoses, alcohol and non-opioid drug-related accidents and overdoses, and violence-related injuries for the second cohort. Using a cross-sectional design, Veterans were followed until the specific outcome of interest was diagnosed, they died, the study ended, or they were lost to follow up. Accelerated failure time models were estimated for each outcome. Membership in persistent moderate days covered and persistent modest days covered trajectories was associated with decreased risk of opioid use disorder (Moderate: θ=0.59, 95%CI:0.54, 0.64; Modest: θ=0.54, 95%CI:0.50, 0.59) and opioid overdose (Moderate: θ=0.67,95%CI: 0.57, 0.79; Modest: θ=0.72, 95%CI:0.61, 0.85) versus higher-utilizing persistent users. Rapid discontinuation was associated with decreased risk of opioid use disorder (θ=0.86, 95% CI:0.77, 0.95) and opioid overdose (θ=0.54, 95%CI:0.41, 0.71), but increased risk of alcohol use disorder (θ=1.07, 95%CI:1.00, 1.15) and other substance use disorders. Delayed discontinuation or delayed reduction was associated with increased risk for most opioid related adverse health events. Persistent use trajectories with low levels of opioid utilization were associated with lower risks of potential opioid-related adverse health events.

The bidirectional relationship between anxiety disorders and alcohol use disorders in adults: Findings from a longitudinal population-based study

BackgroundAnxiety disorders (AD) and alcohol use disorder (AUD) frequently co-occur, but the temporal order of the association is unclear. We have determined the association between AD and the presence and first-onset of AUD, and vice versa. MethodsData were used from n = 6.646 participants and four measurement waves (baseline, 3-, 6- and 9-years) of the Netherlands Mental Health Survey and Incidence Study 2 (NEMESIS-2), a cohort study of the Dutch general population aged 18–64 years. AD and AUD were assessed with the Composite International Diagnostic Interview 3.0. Multilevel logistic autoregressive models were controlled for previous-wave AD or AUD, sociodemographics (Model 1), smoking and clinical factors (Model 2). ResultsPeople with AUD had a higher risk of present (OR = 1.65, 95 % CI 1.11–2.43; Model 2) and first-onset (OR = 2.03, 95 % CI 1.17–3.51; Model 2) AD in 3-years follow-up intervals than people without AUD. Vice versa, people with AD also had a higher sociodemographics-adjusted risk of present and first-onset AUD over 3-years follow-up intervals, but these associations attenuated into insignificance after adjustment for smoking and clinical variables.LimitationsFor statistical power reasons we were not able to analyze 9-year follow-up data or distinguish between AD and AUD types. ConclusionsOur results indicate a bidirectional relationship between AD and AUD; especially those with severe AD (medication use, comorbid depression) are at risk of developing AUD. Health care professionals should focus on prevention of AD in AUD patients and prevention of AUD in patients with (more severe) AD. Further research should investigate the mechanisms underlying the observed associations.

Association of Pro-Ghrelin Leu72Met Polymorphism with Acylated Ghrelin Level and Alcohol Use Disorder: A Preliminary Study

Objective: Multiple environmental and genetic factors contribute to the progression of alcohol use disorder (AUD). Ghrelin is one of the important elements of the brain-gut axis that has been believed to involve in the pathophysiology of addiction. This study aimed to determine whether the GHRL Leu72Met gene polymorphism has an effect on the plasma acylated ghrelin levels in alcohol addicts for the first time.&#x0D; Method: A sample of 50 alcohol-dependent men and 50 controls were enrolled in this study. Acylated ghrelin levels were detected by ELISA kit. The GHRL Leu72Met polymorphism was analyzed by the standard PCR-RFLP method. &#x0D; Results: Acylated ghrelin levels were significantly higher in AUD patients than in controls, and were lower in AUD patients with Leu72Leu than those with Leu72Met and Met72Met. After detoxification, a dramatic decrease was seen in AUD patients having Leu72Met+Met72Met. The presence of 72Met allele was also found to be associated with an increased risk of AUD in Turkish men.&#x0D; Conclusion: It was indicated for the first time that the GHRL Leu72Met variant was associated with higher plasma acylated levels in patients with AUD. The GHRL Leu72 allele compared to the Met72 allele seemed to be protective against AUD in Turkish men. Taken together, despite the small number of subjects evaluated, the findings in this study suggested the effect of the GHRL Leu72Met polymorphism on plasma acylated ghrelin levels and alcohol addiction.

Genetic susceptibility to telomere shortening through the rs2293607 polymorphism is associated with a greater risk of alcohol use disorder

Telomere shortening is usually considered a biomarker of ageing. Harmful alcohol use promotes accelerated biological ageing and alcohol use disorders (AUDs) are associated with short telomere length (TL). This study was conducted to examine the relationship of TL to AUD and determine whether single nucleotide polymorphisms (SNPs) in TERC and TERT modulate this association. For this purpose, we genotyped TERC SNPs rs2293607, rs12696304, and rs16847897 and TERT SNPs rs2735940, rs2736100, and rs2736098 in 308 male patients with AUD and 255 sex-matched healthy controls and measured TL in a subset of 99 patients and 99 controls paired by age and smoking status. Our results showed that the mean TL was shorter in patients with AUD than in controls. The area under the ROC curve was 0.70 (P < 0.001). The GG genotype of TERC rs2293607 was more common among patients with AUD than among controls (9.8% vs. 5.1%; P = 0.038). No difference was found for the other SNPs. Carriers of the GG genotype of rs2293607 had shorter telomeres than did allele A carriers. In conclusion, patients with AUD had shorter telomeres. Genetic susceptibility to telomere shortening through the rs2293607 SNP is associated with a greater risk of AUD.