Global Actions: Commitments to Reduce Harmful Drinking. August 28, 2013

Global Actions in Focus

Drink Driving events in Mexico

Throughout the month of August 2013, the Global Actions Drink Drive Initiative in Mexico has hosted several events to promote the campaign, “Toward Zero Deaths for Drinking and Driving in Puebla.” On August 5 through 9, Global Actions launched a pilot program to present drink driving awareness training to approximately 1,000 students at the Colegio Nacional de Educación Profesional Técnica (CONALEP). The Secretary of Education of Puebla announced that this training will be integrated into courses that are given to students each year as part of their commitment to raise awareness among youth concerning the possible consequences of drink driving and harmful drinking.

Experts, including ICAP Country Manager in Mexico Mariana Guerra Rendon, spoke at a drink driving seminar

In addition to targeting youth, Global Actions also coordinated drink driving training for law enforcement agencies in Puebla on August 17. Approximately 100 representatives from the state and municipal police departments attended the event, along with other first responder personnel. The training was conducted by Dr. Othon Sanchez Cruz, former Director of the Mexico City Police’s “Programa Conduce Sin Alcohol Project”; William Georges, retired Assistant Chief of Police from Albany, New York and road safety consultant; and Mariana Guerra Rendon, ICAP Country Manager in Mexico.

William Georges, retired Assistant Chief of Police from Albany, New York and road safety consultant, delivers training to law enforcement personnel in Puebla

The training seminar focused on how to develop and implement a self-sustaining STOP-DWI program, and also discussed the impacts of traffic enforcement on crime reduction, enforcement techniques, data collection strategies, and youth education efforts within the local area. After the training event, law enforcement officials and agencies were encouraged to strengthen inter-departmental relationships to increase coordination of drink driving interventions.

Key Recent Milestones

· Vietnam: In partnership with the National Traffic Safety Committee (NTSC) and the Thanh Hoa Provincial Traffic Safety Council (TSC), the Global Actions Drink Driving Initiative in Vietnam held the first capacity building workshop in Thanh Hoa City, Thanh Hoa Province, Vietnam on August 16 and 17, 2013.

What's Happening Next

· Colombia: Global Actions will host a drink driving training seminar as part of Phase One of the Patrullero Project in Palmira, Colombia on August 30, 2013.

Using Autopsy Brain Tissue to Study Alcohol-Related Brain Damage in the Genomic Age

The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue.

Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD).

The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases.

Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539).




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Request Reprint E-Mail:    jillian.kril@sydney.edu.au

Intra-VTA Deltorphin, But Not DPDPE, Induces Place Preference in Ethanol-Drinking Rats: Distinct DOR-1 and DOR-2 Mechanisms Control Ethanol Consumption and Reward

 

 While there is a growing body of evidence that the delta opioid receptor (DOR) modulates ethanol (EtOH) consumption, development of DOR-based medications is limited in part because there are 2 pharmacologically distinct DOR subtypes (DOR-1 and DOR-2) that can have opposing actions on behavior.
 

We studied the behavioral influence of the DOR-1-selective agonist [D-Pen²,D-Pen⁵]-Enkephalin (DPDPE) and the DOR-2-selective agonist deltorphin microinjected into the ventral tegmental area (VTA) on EtOH consumption and conditioned place preference (CPP) and the physiological effects of these 2 DOR agonists on GABAergic synaptic transmission in VTA-containing brain slices from Lewis rats.
 

Neither deltorphin nor DPDPE induced a significant place preference in EtOH-naïve Lewis rats. However, deltorphin (but not DPDPE) induced a significant CPP in EtOH-drinking rats. In contrast to the previous finding that intra-VTA DOR-1 activity inhibits EtOH consumption and that this inhibition correlates with a DPDPE-induced inhibition of GABA release, here we found no effect of DOR-2 activity on EtOH consumption nor was there a correlation between level of drinking and deltorphin-induced c
 

These data indicate that the therapeutic potential of DOR agonists for alcohol abuse is through a selective action at the DOR-1 form of the receptor.

hange in GABAergic synaptic transmission.



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Request Reprint E-Mail:    jennifer.mitchell@ucsf.edu

Alcohol Consumption, Heavy Drinking, and Mortality: Rethinking the J-Shaped Curve

High average daily consumption of alcohol has been associated with elevated mortality risk, but more moderate consumption, relative to abstinence, has been associated with reduced mortality risk. However, average daily consumption can be complicated to assess, limiting its usefulness in both research and clinical practice. There are also concerns that average consumption fails to capture the risk associated with certain drinking patterns, such as heavy episodic drinking. This study assessed mortality associated with drinking pattern, operationalized as the frequency of both heavy and nonheavy drinking occasions.
 

Data from the 1997 to 2001 administrations of the National Health Interview Survey (NHIS; n = 111,511) were paired with the current release of the NHIS Linked Mortality Files, which provided mortality follow-up data through the end of 2006. We estimated the impact of drinking pattern on all-cause mortality, operationalized as the frequency of heavy and nonheavy drinking occasions. Other covariates in the model included survey wave, sex, age, race/ethnicity, ratio of family income to poverty threshold, educational attainment, body mass index, and smoking status.

Over a third of past-year drinkers reported heavy drinking. Mortality risk increased steadily as heavy drinking frequency increased; daily heavy drinkers exhibited an almost 2-fold risk of death compared with abstainers . Regular nonheavy drinking was associated with decreased mortality, similar to the “J-shaped curve” highlighted in past research on alcohol mortality; this potential protective effect peaked around 2 nonheavy occasions per week.

 

Any heavy drinking likely elevates mortality risk, and substantial health benefits could be realized by reducing heavy drinking occasions or limiting overall drinking. Heavy and nonheavy drinking frequencies are valid targets for clinical screening and could be helpful in assessing risk and promoting less harmful drinking behavior.


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Request Reprint E-Mail:    plunka@psychiatry.wustl.edu

Personality, cognition and hazardous drinking: Further support for the 2-Component Approach to Reinforcing Substances Model

 


Personality and cognitive processes are both related to alcohol use and misuse. A recent model of hazardous drinking referred, the 2-CARS model, postulates two major pathways to hazardous drinking. One pathway primarily involves the association between Reward Drive and Positive Outcome Expectancies, the second involves the association between Rash Impulsiveness and Drinking Refusal Self-Efficacy.

In previous tests of the model, Drinking Refusal Self-Efficacy was found to have the most proximal impact on drinking, being directly influenced by Rash Impulsiveness, and indirectly influenced by Reward Drive through Positive Outcome Expectancies.

The aim of the current study was to test the 2-CARS model in a larger independent sample.

Results found that individuals with a strong Reward Drive showed higher Positive Outcome Expectancies, while individuals high in Rash Impulsiveness were more likely to report reduced Drinking Refusal Self-Efficacy.

The present results also showed a theoretically unexpected pathway with a direct association between Rash Impulsiveness and Positive Outcome Expectancies.

However, overall the results support the view that a greater understanding of hazardous drinking can be achieved by investigating the relationship between these personality and cognitive variables.




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Request Reprint E-Mail:     p.harnett@psy.uq.edu.au

Mindfulness-Based Relapse Prevention with Racial and Ethnic Minority Women

Racial and ethnic disparities in the treatment of addiction have been acknowledged for several years, yet little is known about which empirically supported treatments for substance use disorders are more or less effective in treating racial and ethnic minority clients.

The current study was a secondary analysis of a randomized clinical trial of two evidence-based treatments, mindfulness-based relapse prevention (MBRP) and relapse prevention (RP), as part of a residential addictions treatment program for women referred by the criminal justice system (N = 70).

At 15-week follow up, regression analyses found that racial and ethnic minority women in MBRP, compared to non-Hispanic and racial and ethnic minority women in RP, reported significantly fewer drug use days (d = .31) and lower addiction severity (d = .65), based on the Addiction Severity Index.

Although the small sample size is a limitation, the results suggest that MBRP may be more efficacious than traditional treatments for racial and ethnic minority women.


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Request Reprint E-Mail:   katiew@unm.edu

The persistence of adolescent binge drinking into adulthood: findings from a 15-year prospective cohort study

 

To examine the prevalence of binge drinking in adolescence and its persistence into adulthood in an Australian cohort.
                              

 15-year prospective cohort study.

 

Victoria, Australia.

 

1943 adolescents were recruited from secondary schools at age 14–15 years.

 

Levels of past-week ‘binge’ drinking (5+ standard drinks on a day, each 10 g alcohol) and ‘heavy binge’ drinking (20+ standard drinks on a day for males, 11+ for females) were assessed during six adolescent waves, and across three adult waves up to age 29 years.

 

Half of the males (52%) and a third of the females (34%) reported past-week adolescent binge drinking. 90% of male and 70% of female adolescent-onset binge drinkers continued to binge in young adulthood; 70% of males and 48% of females who were not adolescent-onset binge drinkers reported young adult binge drinking. Past-week heavy bingeing was less common in adolescence than adulthood. Overall, 35% of the sample (95% CI 33% to 38%) reported past-week binge drinking in adolescence and young adulthood and one-third (33%; 30% to 35%) first reported binge drinking in young adulthood; only 7% of the sample (6–8%) had binge drinking in adolescence but not young adulthood. ‘Heavy binge’ drinking occurred in adolescence and young adulthood for 9% (8% to 10%); 8% (7% to 10%) reported it in adolescence but no longer in young adulthood; and 24% (22% to 26%) began ‘heavy binge’ drinking in young adulthood. Among adolescent binge drinkers (n=821), young adult binge and heavy binge drinking were predicted by being male, adolescent antisocial behaviour and adverse consequences of drinking in adolescence.

 

Binge alcohol use is common and persistent among young Australians. Efforts to prevent the onset of binge drinking during adolescence may substantially reduce harmful patterns of alcohol use in young adulthood.


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The Relationship Between Excessive Alcohol Consumption and Alcohol Use Disorders According to DSM-IV and DSM-5

Although it seems intuitive that alcohol use disorders (AUDs) include excessive alcohol consumption (EAC), this notion is not well established. This study investigates to which degree EAC (defined as >14/21 drinks weekly for women/men and at least three 5+ drinking days per week) and AUD overlap and whether problematic alcohol use groups (EAC-only, AUD-only, and EAC + AUD) differ from each other and from nonproblematic alcohol users regarding sociodemographics, mental health problems, functioning, and service utilization.

 

Data were derived from the Netherlands Mental Health Survey and Incidence Study-2, a population-based study including 5,443 current drinkers (aged 18 to 64) interviewed with the Composite International Diagnostic Interview 3.0. Both DSM-IV AUDs and a proxy of DSM-5 AUD are considered.

Of the current drinkers, 3.8% reported 12-month EAC. Twelve-month prevalence of DSM-IV and DSM-5 AUD were 5.4 and 4.4%, respectively. Regarding DSM-IV, only 17.7% of subjects with AUD reported EAC and 25.3% of those with EAC had an AUD. Compared with nonproblematic alcohol users, the 3 groups of problematic alcohol use (EAC-only, AUD-only, and EAC + AUD) were more often associated with mental health problems, poorer functioning, and service utilization. There were few differences between EAC-only and AUD-only regarding these correlates. However, EAC + AUD had strongest associations with above-mentioned correlates compared with the other 3 groups. Compared with DSM-IV findings, DSM-5 AUDs had slightly larger overlap with EAC, but correlates were similarly associated with problematic alcohol use groups.

 

Findings indicate limited overlap between EAC and AUD. Yet, both dimensions were similarly associated with other problems suggesting that both should be included in future epidemiological research to detect the total group of problematic alcohol users.


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Request Reprint E-Mail:  mtuithof@trimbos.nl 

Repeated Diagnoses of Lifetime Alcohol Use Disorders in a Prospective Study: Insights into the Extent and Nature of the Reliability and Validity Problem

Prior research indicates that assessments of lifetime alcohol use disorders (AUDs) show low sensitivity and are unreliable when assessed by a single, retrospective interview. This study sought to replicate and extend previous research by calculating the lifetime prevalence rate of AUDs using both single retrospective assessments of lifetime diagnosis and repeated assessments of both lifetime and past-year diagnoses over a 16-year period within the same high-risk sample. In addition, this study examined factors that contributed to the consistency in reporting lifetime AUDs over time.

 

Using prospective data, the reliability and validity of lifetime estimates of alcohol dependence and AUD were examined in several ways. Data were drawn from a cohort of young adults at high and low risk for alcoholism, originally ascertained as first-time college freshmen (N = 489 at baseline) at a large, public university and assessed over 16 years.

 

Compared with using a single, lifetime retrospective assessment of DSM-III disorders assessed at approximately age 34, lifetime estimates derived from using multiple, prospective assessments of both past-year and lifetime AUD were substantially higher (25% single lifetime vs. 41% cumulative past-year vs. 46% cumulative lifetime). This pattern of findings was also found when conducting these comparisons at the symptom level. Further, these results suggest that some factors (e.g., symptoms endorsed, prior consistency in reporting of a lifetime AUD, and family history status) are associated with the consistency in reporting lifetime AUDs over time.

 

Based on these findings, lifetime diagnoses using a single measurement occasion should be interpreted with considerable caution given they appear to produce potentially large prevalence underestimates. These results provide further insight into the extent and nature of the reliability and validity problem with lifetime AUDs.


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Request Reprint E-Mail:    amhnq6@mail.missouri.edu

Infant Emotional Withdrawal: A Precursor of Affective and Cognitive Disturbance in Fetal Alcohol Spectrum Disorders

Our aim was to test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother–infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years.

 

The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother–infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Sociodemographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years, cognitive and affective function at 5 and 9 years.

 

Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother–infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all 4 infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ.

 

This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link prenatal alcohol to a specific aspect of infant affective function not attributable to mother–infant interaction, infant temperament, or other socioemotional aspects of the infant's environment and identify infant emotional withdrawal as an early indicator of affective disturbance, particularly in children later diagnosed with FAS and PFAS.


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Request Reprint E-Mail:    molteno.chris@gmail.com

Effects of Ethanol on Immune Response in the Brain: Region-Specific Changes in Adolescent Versus Adult Mice

Alcohol use occurs across the life span beginning in adolescence and continuing through adulthood. Ethanol (EtOH)-induced pathology varies with age and includes changes in neurogenesis, neurodegeneration, and glial cell activation. EtOH-induced changes in glial activation and immune activity are believed to contribute to EtOH-induced neuropathology. Recent studies indicate an emerging role of glial-derived neuroimmune molecules in alcohol abuse and addiction.

Adolescent and adult C57BL/6 mice were treated via gavage with 6 g/kg EtOH for 10 days, and tissue was harvested 1 day post treatment. We compared the effects of EtOH on chemokine and cytokine expression and astrocyte glial fibrillary acidic protein (GFAP) immunostaining and morphology in the hippocampus, cerebellum, and cerebral cortex.

EtOH increased mRNA levels of the chemokine CCL2/MCP-1 in all 3 regions of adult mice relative to controls. The cytokine interleukin-6 (IL-6) was selectively increased only in the adult cerebellum. EtOH did not affect mRNA levels of the cytokine tumor necrosis factor-alpha (TNF-α) in any of these brain regions in adult animals. Interestingly, CCL2, IL-6, and TNF-α mRNA levels were not increased in the hippocampus, cerebellum, or cortex of adolescent mice. EtOH treatment of adult and adolescent mice resulted in increased GFAP immunostaining.

Collectively, these data indicate an age- and region-specific susceptibility to EtOH regulation of neuroinflammatory and addiction-related molecules as well as astrocyte phenotype. These studies may have important implications concerning differential alcohol-induced neuropathology and alcohol addiction across the life span.


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Request Reprint E-Mail:    drewpauld@uams.edu

The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) in the Assessment of Alcohol Use Disorders Among Acute Injury Patients

The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) is a brief alcohol screening test and a candidate for inclusion in recommended screening and brief intervention protocols for acute injury patients. The objective of the current study was to examine the performance of the AUDIT-C to risk stratify injury patients with regard to their probability of having an alcohol use disorder.

 

Participants (n = 1,004) were from a multisite Australian acute injury study. Stratum-specific likelihood ratio (SSLR) analysis was used to examine the performance of previously recommended AUDIT-C risk zones based on a dichotomous cut-point (0 to 3, 4 to 12) and risk zones derived from SSLR analysis to estimate the probability of a current alcohol use disorder.

 

Almost a quarter (23%) of patients met criteria for a current alcohol use disorder. SSLR analysis identified multiple AUDIT-C risk zones (0 to 3, 4 to 5, 6, 7 to 8, 9 to 12) with a wide range of posttest probabilities of alcohol use disorder, from 5 to 68%. The area under receiver operating characteristic curve (AUROC) score was 0.82 for the derived AUDIT-C zones and 0.70 for the recommended AUDIT-C zones. A comparison between AUROCs revealed that overall the derived zones performed significantly better than the recommended zones in being able to discriminate between patients with and without alcohol use disorder.

 

The findings of SSLR analysis can be used to improve estimates of the probability of alcohol use disorder in acute injury patients based on AUDIT-C scores. In turn, this information can inform clinical interventions and the development of screening and intervention protocols in a range of settings.



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Request Reprint E-Mail:   dwade@unimelb.edu.au

Reduction in Central H2O2 Levels Prevents Voluntary Ethanol Intake in Mice: A Role for the Brain Catalase-H2O2 System in Alcohol Binge Drinking

Hydrogen peroxide (H₂O₂) is the cosubstrate used by the enzyme catalase to form Compound I (the catalase-H₂O₂ system), which is the major pathway for the conversion of ethanol (EtOH) into acetaldehyde in the brain. This centrally formed acetaldehyde has been shown to be involved in some of the psychopharmacological effects induced by EtOH in rodents, including voluntary alcohol intake. It has been observed that different levels of this enzyme in the central nervous system (CNS) result in variations in the amount of EtOH consumed. This has been interpreted to mean that the brain catalase-H₂O₂ system, by determining EtOH metabolism, mediates alcohol self-administration. To date, however, the role of H₂O₂ in voluntary EtOH drinking has not been investigated.

 

In the present study, we explored the consequence of a reduction in cerebral H₂O₂ levels in volitional EtOH ingestion. With this end in mind, we injected mice of the C57BL/6J strain intraperitoneally with the H₂O₂ scavengers alpha-lipoic acid (LA; 0 to 50 mg/kg) or ebselen (Ebs; 0 to 25 mg/kg) 15 or 60 minutes, respectively, prior to offering them an EtOH (10%) solution following a drinking-in-the-dark procedure. The same procedure was followed to assess the selectivity of these compounds in altering EtOH intake by presenting mice with a (0.1%) solution of saccharin. In addition, we indirectly tested the ability of LA and Ebs to reduce brain H₂O₂ availability.

 

The results showed that both LA and Ebs dose-dependently reduced voluntary EtOH intake, without altering saccharin consumption. Moreover, we demonstrated that these treatments decreased the central H₂O₂ levels available to catalase.

 

Therefore, we propose that the amount of H₂O₂ present in the CNS, by determining brain acetaldehyde formation by the catalase-H₂O₂ system, could be a factor that determines an animal's propensity to consume EtOH.


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Request Reprint E-Mail:    aragon@psb.uji.es

High Variability in the Exposure of Baclofen in Alcohol-Dependent Patients

Baclofen is a GABA-B receptor agonist used in the treatment of spasticity. Recently, baclofen is used out of its label to decrease craving of alcoholic patients. Its optimal use in these patients requires further pharmacokinetic information. The objective of this study was to characterize the pharmacokinetics of baclofen in alcohol-dependent patients. Randomized clinical trials are ongoing to evaluate the efficacy for this new indication.

 

Thirty-seven outpatients (weight: 74.0 kg [42.0 to 104.0]; age: 49 years [31 to 68]) followed in the addictology unit were studied. Total mean dose of 77.9 mg (30 to 240) per day was administered by oral route. Therapeutic drug monitoring allowed the measurement of 139 plasma concentrations. The following covariates were evaluated: demographic data (age, body weight, height, sex), biological data (creatinine, urea, AST, ALT, albumin, PR, VGM, PAL, CDT, GGT), and tobacco consumption (number of cigarettes and Fagerstrom test). Pharmacokinetic analysis was performed by using a nonlinear mixed-effect population model (NONMEM 7.2 software).

 

Data were modeled with a 1-compartment pharmacokinetic model. The population typical mean (95% confidence interval [95% CI]) values for clearance (CL), apparent volume of distribution (V), and rate constant of absorption (Ka) were 9.9 l/h (9.0 to 11.1), 80.7 l (63.6 to 96.9), and 4.6/h (1.5 to 19.9), respectively. The interindividual variability of CL (95% CI) and V (95% CI), and residual variability (95% CI) were 56.0% (47.9 to 60.7), 68.3% (48.7 to 80.1), and 0.096 mg/l (0.079 to 0.107), respectively.

 

Baclofen exhibited a linear pharmacokinetics with a proportional relationship from 30 to 240 mg per day, the dose range currently used in alcoholic patients. A wide interpatient variability was observed which could not be explained by the covariates. This high variation of baclofen exposure may explain the lack of response observed for some patients.

 

 

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Request Reprint E-Mail:    Amelie.MARSOT@ap-hm.fr

Stress–response pathways are altered in the hippocampus of chronic alcoholics

The chronic high-level alcohol consumption seen in alcoholism leads to dramatic effects on the hippocampus, including decreased white matter, loss of oligodendrocytes and other glial cells, and inhibition of neurogenesis.

Examining gene expression in post mortem hippocampal tissue from 20 alcoholics and 19 controls allowed us to detect differentially expressed genes that may play a role in the risk for alcoholism or whose expression is modified by chronic consumption of alcohol.

We identified 639 named genes whose expression significantly differed between alcoholics and controls at a False Discovery Rate (FDR) ≤ 0.20; 52% of these genes differed by at least 1.2-fold. Differentially expressed genes included the glucocorticoid receptor and the related gene FK506 binding protein 5 (FKBP5), UDP glycosyltransferase 8 (UGT8), urea transporter (SLC14A1), zinc transporter (SLC39A10), Interleukin 1 receptor type 1 (IL1R1), thioredoxin interacting protein (TXNIP), and many metallothioneins.

Pathways related to inflammation, hypoxia, and stress showed activation, and pathways that play roles in neurogenesis and myelination showed decreases. The cortisol pathway dysregulation and increased inflammation identified here are seen in other stress-related conditions such as depression and post-traumatic stress disorder and most likely play a role in addiction.

Many of the detrimental effects on the hippocampus appear to be mediated through NF-κB signaling. Twenty-four of the differentially regulated genes were previously identified by genome-wide association studies of alcohol use disorders; this raises the potential interest of genes not normally associated with alcoholism, such as suppression of tumorigenicity 18 (ST18), BCL2-associated athanogene 3 (BAG3), and von Willebrand factor (VWF).


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Request Reprint  E-Mail:   edenberg@iu.edu

Epigenetics—New Frontier for Alcohol Research

 

 

The term “epigenetics” is rapidly becoming one of the more important watchwords in the field of alcohol research. Put simply, epigenetics is the study of changes in gene function that occur without a change in the body’s genetic code. Instead epigenetic “markers” turn genes “on” and “off.” By acting on these epigenetic markers, environmental factors such as diet, stress, and prenatal nutrition can make an imprint on the genes that are active in different tissues and at various stages of life. Even more importantly, these alterations may be passed along from one generation to the next. The result is that the influences from harmful environmental factors can be extended beyond the individual and passed to his or her offspring. This issue of Alcohol Research: Current Reviewsexplores the concept of epigenetics and how it may influence the body’s response to alcohol and the development of alcohol use disorders and various disease states.

 

 

1 Editors’ Note [PDF]

 

4 In This Issue [PDF]
 

6 Alcohol Metabolism and Epigenetic Changes [PDF]
Samir Zakhari, Ph.D.

 

18 Dysregulation of microRNA Expression and Function Contributes to the Etiology of Fetal Alcohol Spectrum Disorders [PDF]
Sridevi Balaraman, Ph.D.; Joseph D. Tingling; Pai-Chi Tsai; and Rajesh C. Miranda, Ph.D.

 

25 Alcohol, DNA Methylation, and Cancer [PDF]
Marta Varela-Rey, Ph.D.; Ashwin Woodhoo, Ph.D.; Maria-Luz Martinez-Chantar, Ph.D.; José M. Mato, Ph.D.; and Shelly C. Lu, M.D.

 

37 In Utero Alcohol Exposure, Epigenetic Changes, and Their Consequences [PDF]
Michelle Ungerer; Jaysen Knezovich, M.Sc.; and Michele Ramsay, Ph.D.

 

47 Epigenetic Effects of Ethanol on the Liver and Gastrointestinal System [PDF]
Shivendra D. Shukla, Ph.D., and Robert W. Lim, Ph.D.

 

57 Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease [PDF]
Samuel W. French, M.D.

 

69 Epigenetic Control of Gene Expression in the Alcoholic Brain [PDF]
Igor Ponomarev, Ph.D.

 

77 Prenatal Alcohol Exposure and Cellular Differentiation: A Role for Polycomb and Trithorax Group Proteins in FAS Phenotypes? [PDF]
Kylee J. Veazey; Daria Muller; and Michael C. Golding, Ph.D.

 

87 Circadian Disruption: Potential Implications in Inflammatory and Metabolic Diseases Associated With Alcohol [PDF]
Robin M. Voigt, Ph.D.; Christopher B. Forsyth, Ph.D.; and Ali Keshavarzian, M.D.

 

97 Epigenetic Targets for Reversing Immune Defects Caused by Alcohol Exposure [PDF]
Brenda J. Curtis, Ph.D.; Anita Zahs, Ph.D.; and Elizabeth J. Kovacs, Ph.D.

 

114 Glossary [PDF]

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