Risk For Alcohol Dependence Research Articles

Identifying High-Risk Alcohol Users in First-Year College Students: Attitude, Intention, and Facebook.

It is challenging to identify older adolescents at risk for alcohol dependence. This study investigated first-year college students who scored as dependent alcohol users (DAU), and examined their alcohol use and Facebook displays. This longitudinal study recruited college students at two universities to complete a phone interview prior to college (Time 1) and one year later (Time 2). Interviews assessed lifetime and current alcohol use, and attitude (scale of 0=very negative to 6=very positive) and intention (scale of 0=not at all likely to 5=very likely) toward alcohol use. The alcohol use disorders identification test (AUDIT) was administered at Time 2. Facebook profiles were evaluated for the presence of references to alcohol use and intoxication/problematic drinking (I/PD) prior to and throughout the participants first year at the university. Analyses included Chi-squared tests and Wilcoxon sign rank tests. Of 315 participants in the study, a total of 21 (6.7%) of participants met criteria as a DAU at Time 2. DAUs were 54.5% female, 86.4% Caucasian, and 73.7% from University A. At Time 1 all DAUs reported lifetime alcohol use and 91.1% were current drinkers. At Time 2, 95.7% were current drinkers. At Time 1, DAU's mean attitude toward alcohol was 4.0 (SD=1.0) and mean intention was 4.0 (SD=1.4); by Time 2 attitude was 4.6 (SD=0.9), p=0.02, and intention was 4.9 (SD=0.3). At Time 1, 39.1% of DAUs displayed alcohol references on Facebook but only one referenced I/PD. By Time 2, 20 DAU profile owners (90.4%) displayed some reference to alcohol and 52.2% referenced I/PD. Findings suggest areas in which dependence could be identified early, specifically attitude towards alcohol and assessment of Facebook profiles for references to alcohol. These findings have the potential to guide future intervention efforts for this high-risk population.

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.

Perceived Positive Reinforcements Experienced by College Students When Combining Alcohol and Energy Drinks

Combining alcohol with energy drinks has become a common practice among college students. Although much research has focused on expectancies and/or negative consequences of such use, little has examined possible consequences. Because positive consequences may be more predominant than negative consequences when examining the immediate positive reinforcement of drinking behaviors, the role such reinforcement plays in the formation of alcohol abuse and dependence if unknown. Therefore the purpose of this study was to (1) To explore perceived positive reinforcements (PPRs) experienced by drinkers when consuming alcohol-only and combining alcohol with energy drinks and (2) Investigate relationship between PPRs and quantity of drinks. Methods: A convenience sample of 371, 18-24 year old college students completed an online survey containing demographic questions, quantity/frequency index, and the Positive drinking consequences questionnaire for alcoholonly and combined use. Results: Combined Users (CUs) reported significantly more PPR(s) than alcohol-only users (AOUs), but reported more PPRs when consuming alcohol-only. PPR(s) did not significantly increase with greater quantities of alcohol in AOUs, but did increase among CUs when consuming alcohol-only and combined drinks. Conclusions: CU derived significantly more PPR(s) than AOUs, suggesting they hold expectancies and experience outcomes different from those of AOUs. Thus CUs may represent a special population at higher risk for alcohol abuse and dependence. Incorporating PPR(s) into current alcohol treatment and prevention practices represents an unexplored avenue with great potential to transform the college drinking culture.

Caudate Volume in Offspring at Ultra High Risk for Alcohol Dependence: COMT Val158Met, DRD2, Externalizing Disorders, and Working Memory*

There is emerging evidence that the increased susceptibility to developing alcohol and substance use disorders in those with a family history of Alcohol Dependence (AD) may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing. Externalizing disorders of childhood including Attention Deficit Hyperactivity Disorder, Conduct and Oppositional Disorders are a prominent feature of those with a positive family history. The caudate nuclei have been implicated in both the salience of rewards and in the pathophysiology of alcohol dependence and these often antecedent childhood disorders. Adolescent/young adult high and low-risk for AD offspring (N = 130) were studied using magnetic resonance imaging. Volumes of the caudate nucleus were obtained using manual tracing with BRAINS2 software and neuropsychological functioning determined. Childhood disorders were assessed as part of a long-term longitudinal follow-up that includes young adult assessment. Dopaminergic variation was assessed using genotypic variation in the catechol-O-methyltransferase (COMT) and DRD2 genes. High-risk subjects showed poorer Working Memory functioning. Cau-date volume did not differ between high and low-risk subjects, but those with externalizing disorders of childhood showed reduced caudate volume. Variation in COMT and DRD2 genes was associated with Working Memory performance and caudate volume. Caudate volume is reduced in association with externalizing disorders of childhood/adolescence. Working Memory deficits appear in familial high-risk offspring and those with externalizing disorders of childhood. The dopaminergic system appears to be involved in both working memory performance and externalizing disorders of childhood.

Relationship between Motor Threshold and Externalizing Symptoms in Subjects at High Risk for Alcohol Dependence: A TMS Study

Relationship between Motor Threshold and Externalizing Symptoms in Subjects at High Risk for Alcohol Dependence: A TMS Study

Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction

Alcohol abuse is associated with long-term reductions in fronto-cortical volume and limbic metabolism. However, an unanswered question in alcohol research is whether these alterations are the sole consequence of chronic alcohol use, or contain heritable contributions reflecting biological propensity toward ethanol addiction. Animal models of genetic predisposition to alcohol dependence can be used to investigate the role of inborn brain abnormalities in the aetiology of alcoholism. Here we used magnetic resonance imaging (MRI) in the Marchigian-Sardinian (msP) alcohol-preferring rats to assess the presence of inherited structural or functional brain alterations. Alcohol-naïve msP (N=22) and control rats (N=26) were subjected to basal cerebral blood volume (bCBV) mapping followed by voxel-based morphometry (VBM) of grey matter and tract-based spatial statistics mapping of white matter fractional anisotropy. msP rats exhibited significantly reduced bCBV, an established marker of resting brain function, in focal cortico-limbic and thalamic areas, together with reduced grey matter volume in the thalamus, ventral tegmental area, insular and cingulate cortex. No statistically significant differences in fractional anisotropy were observed between groups. These findings highlight the presence of inborn grey matter and metabolic abnormalities in alcohol-naïve msP rats, the localization and sign of which are remarkably similar to those mapped in abstinent alcoholics and subjects at high risk for alcohol dependence. Collectively, these results point for a significant role of heritable neurofunctional brain alterations in biological propensity toward ethanol addiction, and support the translational use of advanced imaging methods to describe the circuital determinants of vulnerability to drug addiction.

A large-scale meta-analysis of the association between the ANKK1/DRD2 Taq1A polymorphism and alcohol dependence

Alcohol dependence (AD) is a common neuropsychiatric disorder with high heritability. A number of studies have analyzed the association between the Taq1A polymorphism (located in the gene cluster ANKK1/DRD2) and AD. In the present study, we conducted a large-scale meta-analysis to confirm the association between the Taq1A polymorphism and the risk for AD in over 18,000 subjects included in 61 case-control studies that were published up to August 2012. Our meta-analysis demonstrated both allelic and genotypic association between the Taq1A polymorphism and AD susceptibility [allelic: P(Z) = 1.1 × 10(-5), OR = 1.19; genotypic: P(Z) = 3.2 × 10(-5), OR = 1.24]. The association remained significant after adjustment for publication bias using the trim and fill method. Sensitivity analysis showed that the effect size of the Taq1A polymorphism on AD risk was moderate and not influenced by any individual study. The pooled odds ratio from published studies decreased with the year of publication, but stabilized after the year 2001. Subgroup analysis indicated that publication bias could be influenced by racial ancestry. In summary, this large-scale meta-analysis confirmed the association between the Taq1A polymorphism and AD. Future studies are required to investigate the functional significance of the ANKK1/DRD2 Taq1A polymorphism in AD.

Effects of adolescent onset voluntary drinking followed by ethanol vapor exposure on subsequent ethanol consumption during protracted withdrawal in adult Wistar rats

Epidemiological studies have demonstrated that heavy drinking and alcohol abuse and dependence peak during the transition between late adolescence and early adulthood. The objective of the present study was to determine whether a model of early onset adolescent ethanol drinking exposure that is followed by an ethanol vapor regimen during late adolescence and young adulthood leads to an increase in drinking in adulthood. In this model, initiation of voluntary ethanol drinking in adolescence, using a sweetened solution, was followed by an 8-wk intermittent ethanol vapor regimen in Wistar rats. A limited-access two-bottle choice paradigm was then used to measure intake of a 10% (w/v) ethanol solution. No differences in water intake (g/kg), total fluid intake (ml/kg) and body weight (g) were observed between air-exposed and ethanol-vapor exposed groups during the pre-vapor and post-vapor phases. The 8weeks of ethanol vapor exposure was found to produce only a modest, but statistically significant, elevation of ethanol intake during the protracted withdrawal period, compared to air-exposed rats. A significant increase in ethanol preference ratio was also observed in ethanol-vapor exposed rats during the sucrose-fading phase, but not during the protracted withdrawal period. The findings from the present study suggest that in addition to alcohol exposure, environmental variables that impact appetitive as well as consumptive behaviors may be important in developing robust drinking effects that model, in animals, the increased risk for alcohol dependence seen in some human adolescents who begin drinking at an early age.

A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53.

Several studies have identified genes associated with alcohol-use disorders (AUDs), but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism to identify novel genes affecting risk for alcohol dependence (AD). To maximize the power of the extended family design, we used a quantitative endophenotype, measured in all individuals: number of alcohol-dependence symptoms endorsed (symptom count (SC)). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with SC were also associated with the dichotomous phenotype, DSM-IV AD. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol-dependence symptom counts (P=4.5 × 10(-8), inflation-corrected P=9.4 × 10(-7)). Results with DSM-IV AD in the regions of interest support our findings with SC, although the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: nonoverlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian Twin Family Study of AUDs (OZALC). Nominal association of C15orf53 with SC was observed in SAGE. The variant that showed strongest association with SC, rs12912251 and its highly correlated variants (D'=1, r(2) 0.95), have previously been associated with risk for bipolar disorder.

Family history of alcohol dependence modulates functional neurophysiology in mood/anxiety disorders

A family history (FH) of alcohol dependence (AD) not only increases the risk for AD, but is also associated with an increased risk for mood and anxiety disorders. However, it is unknown how a FH of AD affects neural substrates in patients with mood and anxiety disorders. In this study we examined the effects of an alcoholic FH on cognitive and emotional functions in these patients using functional magnetic resonance imaging (fMRI). Method In a sample of non-alcoholic patients with depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) neuroimaging study, patients with a first-degree FH of AD (FH+; n=31) were compared with patients without a FH (FH-; n=77) on performance and brain activation during visuospatial planning and emotional word encoding. Results were compared with those of healthy controls (HCs) without a FH of AD (n=31). FH+ patients performed slower during planning with increasing task load, coupled with stronger blood oxygen level-dependent responses in dorsal prefrontal areas compared with FH- patients and HCs. FH was not associated with performance differences during word encoding, but right insula activation during positive word encoding was present in FH+ patients, comparable with HCs, but absent in FH- patients. This study demonstrates subtle impairments during planning in FH+ compared with FH- patients and HCs, whereas activation during mood-incongruent stimuli in FH+ patients was similar to HCs but not FH- patients, suggesting that the presence of a FH of AD is a useful marker for the neurophysiological profile in mood/anxiety disorders and possible predictor for treatment success.

Rare ADH Variant Constellations are Specific for Alcohol Dependence

Some of the well-known functional alcohol dehydrogenase (ADH) gene variants (e.g. ADH1B*2, ADH1B*3 and ADH1C*2) that significantly affect the risk of alcohol dependence are rare variants in most populations. In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF) <0.05] and alcohol dependence, with several other neuropsychiatric and neurological disorders as reference. A total of 49,358 subjects in 22 independent cohorts with 11 different neuropsychiatric and neurological disorders were analyzed, including 3 cohorts with alcohol dependence. The entire ADH gene cluster (ADH7-ADH1C-ADH1B-ADH1A-ADH6-ADH4-ADH5 at Chr4) was imputed in all samples using the same reference panels that included whole-genome sequencing data. We stringently cleaned the phenotype and genotype data to obtain a total of 870 single nucleotide polymorphisms with 0< MAF <0.05 for association analysis. We found that a rare variant constellation across the entire ADH gene cluster was significantly associated with alcohol dependence in European-Americans (Fp1: simulated global P=0.045), European-Australians (Fp5: global P=0.027; collapsing: P=0.038) and African-Americans (Fp5: global P=0.050; collapsing: P=0.038), but not with any other neuropsychiatric disease. Association signals in this region came principally from ADH6, ADH7, ADH1B and ADH1C. In particular, a rare ADH6 variant constellation showed a replicable association with alcohol dependence across these three independent cohorts. No individual rare variants were statistically significantly associated with any disease examined after group- and region-wide correction for multiple comparisons. We conclude that rare ADH variants are specific for alcohol dependence. The ADH gene cluster may harbor a causal variant(s) for alcohol dependence.

Behavioral genetics and population health interventions for alcohol problems: at odds or oddly in agreement?

This commentary argues that findings from behavioral genetics research can be reconciled with population health approaches to dealing with alcohol problems. Such a contention may seem counterintuitive, as these approaches to the causes of, and responses to, alcohol problems appear to be at odds with one another. Studies on behavioral genetics found that ~50–70% of the population variability in the risk for alcohol dependence can be attributed to genetic influences.1 Biomedical advocacy groups align these findings with definitions of alcohol dependence as a brain disease and state that medical approaches are the ideal way to deal with this issue.

ALCOHOL CONSUMPTION AND MAJOR DEPRESSION IN THE GENERAL POPULATION: THE CRITICAL IMPORTANCE OF DEPENDENCE

Substance use disorders and major depressive episodes (MDEs) often co-occur. Alcohol consumption may contribute to the aetiology of depressive episodes and/or vice versa. In Canada, the National Population Health Survey (NPHS) evaluated several aspects of alcohol use and MDE in a large population cohort over 12 years of follow-up. We evaluated the incidence of MDE in relation to different patterns of alcohol use, and examined the incidence of alcohol misuse in respondents with and without MDE. The NPHS is a longitudinal study that began data collection in 1994 and whose cohort has been followed with biannual interviews. These interviews assess MDE using the Composite International Diagnostic Interview Short Form for Major Depression (CIDI-SFMD). Another CIDI-SF module assessed alcohol dependence during two interviews. Any alcohol consumption, exceeding moderate drinking guidelines and binge drinking were also assessed. We used logistic regression and proportional hazards models to assess longitudinal relationships between these variables Respondents with alcohol dependence were at higher risk of MDE, but any alcohol consumption, exceeding guidelines for moderate drinking and binge drinking were not. Respondents with MDE showed no increase of alcohol consumption, but the risk of alcohol dependence was elevated in depressed men. Of direct clinical significance is the bidirectional relationship between alcohol dependence and MDE. Associations between alcohol consumption and MDE were not observed except when dependence was indicated. Alcohol dependence increased the risk of MDE, and MDE increased the risk of alcohol dependence, but only in men.

Relationship between Motor Threshold and Externalizing Symptoms in Subjects at High Risk for Alcohol Dependence: A TMS Study

The American Journal on AddictionsVolume 22, Issue 1 p. 84-85 Letter to the Editor Relationship between Motor Threshold and Externalizing Symptoms in Subjects at High Risk for Alcohol Dependence: A TMS Study Kesavan Muralidharan MD, Corresponding Author Kesavan Muralidharan MD Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDr. Muralidharan, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T2A1. E-mail: muralidharan.kesavan@ubc.ca.Search for more papers by this authorGanesan Venkatasubramanian MD, Ganesan Venkatasubramanian MD Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaSearch for more papers by this authorPramod K. Pal DM, Pramod K. Pal DM Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaSearch for more papers by this authorVivek Benegal DPM, MD, Vivek Benegal DPM, MD Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaSearch for more papers by this author Kesavan Muralidharan MD, Corresponding Author Kesavan Muralidharan MD Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDr. Muralidharan, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T2A1. E-mail: muralidharan.kesavan@ubc.ca.Search for more papers by this authorGanesan Venkatasubramanian MD, Ganesan Venkatasubramanian MD Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaSearch for more papers by this authorPramod K. Pal DM, Pramod K. Pal DM Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaSearch for more papers by this authorVivek Benegal DPM, MD, Vivek Benegal DPM, MD Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaSearch for more papers by this author First published: 07 February 2013 https://doi.org/10.1111/j.1521-0391.2013.00274.xCitations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume22, Issue1January‐February 2013Pages 84-85 RelatedInformation

Relationships among parental monitoring and sensation seeking on the development of substance use disorder among college students

Substance use disorder is a serious health problem that tends to manifest in late adolescence. Attempting to influence targetable risk and protective factors holds promise for prevention and treatment. Survey data from 1253 college students (48.5% male, 26.9% non-White) were used to investigate the independent and combined effects of two prominent factors, sensation seeking and parental monitoring, on the probability of alcohol and/or cannabis dependence during the first year of college. In multivariate analyses that controlled for high school use, gender, race, mother's education, and importance of religion, retrospective reports by the student of parental behavior during the last year of high school indicated that higher levels of parental monitoring had a direct effect on reducing risk for alcohol dependence during the first year of college, but not on cannabis dependence. High levels of sensation seeking were associated with increased risk for both alcohol and cannabis dependence. No interaction effects were found. The results extend prior findings by highlighting influences of pre-college parental monitoring and sensation seeking on the probability of alcohol and/or cannabis dependence during the first year of college. The findings also suggest that these two factors are useful in identifying college students at high risk for alcohol and/or cannabis dependence.

Hypermethylation of OPRM1 promoter region in European Americans with alcohol dependence

The μ-opioid receptor mediates rewarding effects of alcohol and illicit drugs. We hypothesized that altered DNA methylation in the μ-opioid receptor gene (OPRM1) might influence the vulnerability to alcohol dependence (AD). Genomic DNA was extracted from the peripheral blood of 125 European Americans with AD and 69 screened European American controls. Methylation levels of 16 CpGs in the OPRM1 promoter region were examined by bisulfite sequencing analysis. A multivariate analysis of covariance was conducted to analyze AD-associated methylation changes in the OPRM1 promoter region, using days of intoxication in the past 30 days, sex, age, ancestry proportion and childhood adversity (CA) as covariates. Three CpGs (80, 71, and 10 bp upstream of the OPRM1 translation start site) were more highly methylated in AD cases than in controls (CpG-80: P=0.033; CpG-71: P=0.004; CpG-10: P=0.008). Although these sites were not significant after correction for multiple comparisons, the overall methylation level of the 16 CpGs was significantly higher in AD cases (13.6%) than in controls (10.6%) (P=0.049). Sex and CA did not significantly influence OPRM1 promoter methylation levels. Our findings suggest that OPRM1 promoter hypermethylation may increase the risk for AD and other substance dependence disorders.

Combined role of childhood maltreatment, family history, and gender in the risk for alcohol dependence

Studies of the relationship between childhood maltreatment and alcohol dependence have not controlled comprehensively for potential confounding by co-occurring maltreatments and other childhood trauma, or determined whether parental history of alcohol disorders operates synergistically with gender and maltreatment to produce alcohol dependence. We addressed these issues using national data. Method Face-to-face surveys of 27 712 adult participants in a national survey. Childhood physical, emotional and sexual abuse, and physical neglect were associated with alcohol dependence (p<0.001), controlling for demographics, co-occurring maltreatments and other childhood trauma. Attributable proportions (APs) due to interaction between each maltreatment and parental history revealed significant synergistic relationships for physical abuse in the entire sample, and for sexual abuse and emotional neglect in women (APs, 0.21, 0.31, 0.26 respectively), indicating that the odds of alcohol dependence given both parental history and these maltreatments were significantly higher than the additive effect of each alone (p<0.05). Childhood maltreatments independently increased the risk of alcohol dependence. Importantly, results suggest a synergistic role of parental alcoholism: the effect of physical abuse on alcohol dependence may depend on parental history, while the effects of sexual abuse and emotional neglect may depend on parental history among women. Findings underscore the importance of early identification and prevention, particularly among those with a family history, and could guide genetic research and intervention development, e.g. programs to reduce the burden of childhood maltreatment may benefit from addressing the negative long-term effects of maltreatments, including potential alcohol problems, across a broad range of childhood environments.

Alcohol attentional bias is associated with autonomic indices of stress-primed alcohol cue-reactivity in alcohol-dependent patients.

When alcohol-dependent individuals are exposed to drinking-related cues, they exhibit psychophysiological reactivity such as changes in heart rate variability (HRV) and skin temperature. Moreover, such alcohol cue-reactivity may co-occur with attentional bias (AB) toward alcohol cues. In turn, stress may promote appetitive responses by exacerbating these autonomic and attentional factors. Although cue-reactivity paradigms have been used for decades to probe such automatic appetitive processes in persons with alcohol-use disorders, less is known about the attentional correlates of alcohol cue-reactivity. In this study, alcohol-dependent adults (N = 58) recruited from a residential treatment facility completed a spatial cueing task as a measure of alcohol AB and affect-modulated cue-reactivity protocol. Multiple linear regression analyses revealed that alcohol AB was significantly positively associated with parasympathetically mediated HRV and finger temperature slope and inversely associated with sympathetically mediated HRV during stress-primed alcohol cue-exposure, independent of alcohol dependence severity, time in treatment, alcohol craving, and perceived stress. Study findings suggest that alcohol AB is linked with physiological cue-reactivity and that different attentional strategies are associated with distinct profiles of autonomic responses that may ultimately index or confer additional risk for alcohol dependence.

DRD2 C957T and TaqIA Genotyping Reveals Gender Effects and Unique Low-Risk and High-Risk Genotypes in Alcohol Dependence

As recent conflicting reports describe a genetic association between both the C- and the T-alleles of the dopamine D2 receptor (DRD2) C957T polymorphism (rs6277) in alcohol-dependent subjects, our aim was to examine this polymorphism and TaqIA (rs1800497) in Australian alcohol-dependent subjects. The C957T polymorphism was genotyped in 228 patients with alcohol dependence (72 females and 156 males) and 228 healthy controls. The C-allele and C/C genotype of C957T was associated with alcohol dependence, whereas the TaqIA polymorphism was not. When analysed separately for C957T, males showed an even stronger association with the C-allele and females showed no association. The C957T and TaqIA haplotyping revealed a strong association with alcohol dependence and a double-genotype analysis (combining C957T and TaqIA genotypes) revealed that the relative risk of different genotypes varied by up to 27-fold with the TT/A1A2 having an 8.5-fold lower risk of alcohol dependence than other genotypes. Decreased DRD2 binding associated with the C-allele of the DRD2 C957T polymorphism is likely to be important in the underlying pathophysiology of at least some forms of alcohol dependence, and this effect appears to be limited to males only.

Developmental Trajectory and Environmental Moderation of the Effect of ALDH2 Polymorphism on Alcohol Use

In the aldehyde dehydrogenase 2 (ALDH2) gene, the ALDH2*2 allele, prevalent in East Asian populations, encodes an enzyme with severely reduced activity, thereby disrupting the normal metabolism of alcohol. Possession of the ALDH2*2 allele has been repeatedly shown to be associated with lower risk for alcohol dependence and reduced alcohol use. However, relatively few studies have considered whether the magnitude of the effect of ALDH2 polymorphism upon drinking is related to developmental stage or varies by environmental context. In a longitudinally assessed sample of 356 adopted adolescents and young adults of East Asian descent, we examined the progression over time of the relationship between ALDH2 genotype and multiple measures of drinking behavior. We also sought to determine whether the environmental influences of nonbiological parent and elder sibling alcohol use and misuse, as well as deviant peer behavior, moderated the effect of ALDH2 genotype upon alcohol use. Across all measures of alcohol use, the association between ALDH2*2 allele possession and reduced drinking went from negligible to moderate between mid-adolescence and early adulthood. A combined index of adoptive parent alcohol use and misuse consistently moderated the protective effect of the ALDH2*2 allele across the measures of quantity and frequency of alcohol use, and symptomology, such that high parental alcohol use and misuse reduced the protective effect of the ALDH2*2 allele, while low parental alcohol use and misuse enhanced the effect of the allele. Neither a combined index of elder sibling alcohol use and misuse, nor deviant peer behavior was consistently related to the effect of ALDH2 genotype. The protective effect of the ALDH2*2 allele increases over the course of adolescence and young adulthood and is modified by the environmental influence of parental alcohol use and misuse. As such, ALDH2 provides a model system for exploring the nature of gene-environment interplay across development.