Are the 1976–1985 birth cohorts heavier drinkers? Age-period-cohort analyses of the National Alcohol Surveys 1979–2010

To estimate age-period-cohort models predicting alcohol volume, heavy drinking and beverage-specific alcohol volume in order to evaluate whether the 1976–1985 birth cohorts drink relatively heavily.

 

Data from seven cross-sectional surveys of the USA conducted between 1979 and 2010 were utilized in negative binomial generalized linear models of age, period and cohort effects predicting alcohol measures.

 

General population surveys of the USA.

 

Thirty-six thousand four hundred and thirty-two US adults (aged 18 years or older).

 

Monthly number of alcohol drinks, beer, wine and spirits drinks, and days drinking five or more drinks in the past year derived from beverage-specific graduated frequency questions.

 

Relative to the reference 1956–60 birth cohort, men in the 1976–1980 cohort for were found to consume more alcohol [incidence rate ratio (IRR) = 1.222: confidence interval (CI) 1.07–1.39) and to have more 5+ days (the number of days having five or more drinks) (IRR = 1.365: CI 1.09–1.71) as were men in the 1980–85 cohort for volume (IRR = 1.284: CI 1.10–1.50) and 5+ days (IRR = 1.437: CI 1.09–1.89). For women, those in the 1980–85 cohort were found to have higher alcohol volume (IRR = 1.299: CI 1.07–1.58) and more 5+ days (IRR = 1.547: CI 1.01–2.36). Beverage-specific models found different age patterns of volume by beverage with a flat age pattern for both genders' spirits and women's wine, an increasing age pattern for men's wine and a declining age pattern from those in their early 20s for beer.

 

In the USA, men born between 1976 and 1985, and women born between 1981 and 1985 have higher alcohol consumption than in earlier or later years.


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Request Reprint E-Mail:    wkerr@arg.org

Gene specific modifications unravel ethanol and acetaldehyde actions

Ethanol is metabolized into acetaldehyde mainly by the action of alcohol dehydrogenase in the liver, while mainly by the action of catalase in the brain. Aldehyde dehydrogenase-2 metabolizes acetaldehyde into acetate in both organs.

Gene specific modifications reviewed here show that an increased liver generation of acetaldehyde (by transduction of a gene coding for a high-activity liver alcohol dehydrogenase ADH1*B2) leads to increased blood acetaldehyde levels and aversion to ethanol in animals.

Similarly aversive is an increased acetaldehyde level resulting from the inhibition of liver aldehyde dehydrogenase-2 (ALDH2) synthesis (by an antisense coding gene against aldh2 mRNA).

The situation is diametrically different when acetaldehyde is generated in the brain. When the brain ventral tegmental area (VTA) is endowed with an increased ability to generate acetaldehyde (by transfection of liver rADH) the reinforcing effects of ethanol are increased, while a highly specific inhibition of catalase synthesis (by transduction of a shRNA anti catalase mRNA) virtually abolishes the reinforcing effects of ethanol as seen by a complete abolition of ethanol intake in rats bred for generations as high ethanol drinkers.

Data shows two divergent effects of increases in acetaldehyde generation: aversive in the periphery but reinforcing in the brain.


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Addiction is a reward deficit and stress surfeit disorder

Drug addiction can be defined by a three-stage cycle—binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation—that involves allostatic changes in the brain reward and stress systems.

Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process. The negative emotional state that drives negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain reward and stress systems.

Specific neurochemical elements in these structures include not only decreases in reward system function (within-system opponent processes) but also recruitment of the brain stress systems mediated by corticotropin-releasing factor (CRF) and dynorphin-κ opioid systems in the ventral striatum, extended amygdala, and frontal cortex (both between-system opponent processes).

CRF antagonists block anxiety-like responses associated with withdrawal, block increases in reward thresholds produced by withdrawal from drugs of abuse, and block compulsive-like drug taking during extended access. Excessive drug taking also engages the activation of CRF in the medial prefrontal cortex, paralleled by deficits in executive function that may facilitate the transition to compulsive-like responding.

Neuropeptide Y, a powerful anti-stress neurotransmitter, has a profile of action on compulsive-like responding for ethanol similar to a CRF1 antagonist.

Blockade of the κ opioid system can also block dysphoric-like effects associated with withdrawal from drugs of abuse and block the development of compulsive-like responding during extended access to drugs of abuse, suggesting another powerful brain stress system that contributes to compulsive drug seeking.

The loss of reward function and recruitment of brain systems provide a powerful neurochemical basis that drives the compulsivity of addiction.


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Modeling alcohol use disorder severity: an integrative structural equation modeling approach

Alcohol dependence is a complex psychological disorder whose phenomenology changes as the disorder progresses. Neuroscience has provided a variety of theories and evidence for the development, maintenance, and severity of addiction; however, clinically, it has been difficult to evaluate alcohol use disorder (AUD) severity. 

This study seeks to evaluate and validate a data-driven approach to capturing alcohol severity in a community sample. 

Participants were non-treatment seeking problem drinkers (n = 283). A structural equation modeling (SEM) approach was used to (a) verify the latent factor structure of the indices of AUD severity; and (b) test the relationship between the AUD severity factor and measures of alcohol use, affective symptoms, and motivation to change drinking. 

The model was found to fit well, with all chosen indices of AUD severity loading significantly and positively onto the severity factor. In addition, the paths from the alcohol use, motivation, and affective factors accounted for 68% of the variance in AUD severity. Greater AUD severity was associated with greater alcohol use, increased affective symptoms, and higher motivation to change.

Unlike the categorical diagnostic criteria, the AUD severity factor is comprised of multiple quantitative dimensions of impairment observed across the progression of the disorder. The AUD severity factor was validated by testing it in relation to other outcomes such as alcohol use, affective symptoms, and motivation for change. Clinically, this approach to AUD severity can be used to inform treatment planning and ultimately to improve outcomes.


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Expression, covariation, and genetic regulation of miRNA Biogenesis genes in brain supports their role in addiction, psychiatric disorders, and disease

The role of miRNA and miRNA biogenesis genes in the adult brain is just beginning to be explored. In this study we have performed a comprehensive analysis of the expression, genetic regulation, and co-expression of major components of the miRNA biogenesis pathway using human and mouse data sets and resources available on the GeneNetwork web site (genenetwork.org).

We found a wide range of variation in expression in both species for key components of the pathway—Drosha, Pasha, and Dicer. Across species, tissues, and expression platforms all three genes are generally well-correlated.

No single genetic locus exerts a strong and consistent influence on the expression of these key genes across murine brain regions. However, in mouse striatum, many members of the miRNA pathway are correlated—including Dicer, Drosha, Pasha, Ars2 (Srrt), Eif2c1 (Ago1), Eif2c2 (Ago2), Zcchc11, and Snip1. The expression of these genes may be partly influenced by a locus on Chromosome 9 (105.67–106.32 Mb).

We explored ~1500 brain phenotypes available for the C57BL/6J × DBA/2J (BXD) genetic mouse population in order to identify miRNA biogenesis genes correlated with traits related to addiction and psychiatric disorders.

We found a significant association between expression of Dicer and Drosha in several brain regions and the response to many drugs of abuse, including ethanol, cocaine, and methamphetamine.

Expression of Dicer, Drosha, and Pasha in most of the brain regions explored is strongly correlated with the expression of key members of the dopamine system. Drosha, Pasha, and Dicer expression is also correlated with the expression of behavioral traits measuring depression and sensorimotor gating, impulsivity, and anxiety, respectively.

Our study provides a global survey of the expression and regulation of key miRNA biogenesis genes in brain and provides preliminary support for the involvement of these genes and their product miRNAs in addiction and psychiatric
disease processes.


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Alcohol, Moods and Male–Female Differences: Daily Interactive Voice Response over 6 Months

The goal of this study was to better understand the predictive relationship in both directions between negative (anger, sadness) and positive (happiness) moods and alcohol consumption using daily process data among heavy drinkers. 

Longitudinal daily reports of moods, alcohol use and other covariates such as level of stress were assessed over 180 days using interactive voice response telephone technology. Participants were heavy drinkers (majority meeting criteria for alcohol dependence at baseline) recruited through their primary care provider. The sample included 246 (166 men, 80 women) mostly Caucasian adults. Longitudinal statistical models were used to explore the varying associations between number of alcoholic drinks and mood scores the next day and vice versa with gender as a moderator. 

Increased alcohol use significantly predicted decreased happiness the next day (P < 0.005), more strongly for females than males. Increased anger predicted higher average alcohol use the next day for males only (P< 0.005). 

This daily process study challenges the notion that alcohol use enhances positive mood for both males and females. Our findings also suggest a strong association between anger and alcohol use that is specific to males. Thus, discussions about the effects of drinking on one's feeling of happiness may be beneficial for males and females as well as anger interventions may be especially beneficial for heavy-drinking male.


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Request Reprint E-Mail:   valerie.harder@uvm.edu 

Empirical Derived AUD Sub Types in the US general population: A Latent Class Analysis

 

 

This study examined the homogenous expression of DSM-5 based alcohol use disorder (AUD) latent subtypes.

 

Using data from the NESARC Wave 2 (n = 22,177) the typology was established utilising latent class analysis (LCA) and the model was further validated by multivariate regression on a range of covariates.

 

Three AUD classes based on a severity gradient and one non-problematic class was the most parsimonious description of the data. These classes displayed both quantitative and qualitative differences on the covariates.

 

The resulting typology has high clinical utility, enhances AUD classification and adds to our understanding of AUD trajectories, prevention and treatment.

 

 

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Request Reprint E-Mail:     Casey-m4@email.ulster.ac.uk

Longitudinal Prediction of Divorce in Russia: The Role of Individual and Couple Drinking Patterns

 
The aim of the study was to explore associations between dimensions of alcohol use in married couples and subsequent divorce in Russia using longitudinal data. 

Follow-up data on 7157 married couples were extracted from 14 consecutive annual rounds (1994–2010) of the Russian Longitudinal Monitoring Survey, a national population-based panel study. Discrete-time hazard models were fitted to estimate the probability of divorce among married couples by drinking patterns reported in the previous survey wave. 

 In adjusted models, increased odds of divorce were associated with greater frequency of husband and wife drinking (test for trend P = 0.005, and P= 0.05, respectively), wife's binge drinking (P = 0.05) and husband's heavy vodka drinking (P = 0.005). Couples in whom the wife drank more frequently than the husband were more likely to divorce (OR 2.86, 95% CI 1.52–5.36), compared with other combinations of drinking. The association between drinking and divorce was stronger in regions outside Moscow or St. Petersburg. 

This study adds to the sparse literature on the topic and suggests that in Russia heavy and frequent drinking of both husbands and wives put couples at greater risk of future divorce, with some variation by region and aspect of alcohol use.


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Request Reprint E-Mail:   katherine.keenan@lshtm.ac.uk

GluN2B in corticostriatal circuits governs choice learning and choice shifting.

 

A choice that reliably produces a preferred outcome can be automated to liberate cognitive resources for other tasks. Should an outcome become less desirable, behavior must adapt in parallel or it becomes perseverative. Corticostriatal systems are known to mediate choice learning and flexibility, but the molecular mechanisms of these processes are not well understood.

We integrated mouse behavioral, immunocytochemical, in vivo electrophysiological, genetic and pharmacological approaches to study choice.

We found that the dorsal striatum (DS) was increasingly activated with choice learning, whereas reversal of learned choice engaged prefrontal regions. In vivo, DS neurons showed activity associated with reward anticipation and receipt that emerged with learning and relearning. Corticostriatal or striatal deletion of Grin2b (encoding the NMDA-type glutamate receptor subunit GluN2B) or DS-restricted GluN2B antagonism impaired choice learning, whereas cortical Grin2b deletion or OFC GluN2B antagonism impaired shifting.

Our convergent data demonstrate how corticostriatal GluN2B circuits govern the ability to learn and shift choice behavior.


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Request Reprint E-Mail:    Andrew.Holmes@nih.gov

Overcoming Addictions, a Web-Based Application, and SMART Recovery, an Online and In-Person Mutual Help Group for Problem Drinkers, Part 1: Three-Month Outcomes of a Randomized Controlled Trial

Overcoming Addictions (OA) is an abstinence-oriented, cognitive behavioral, Web application based on the program of SMART Recovery. SMART Recovery is an organization that has adapted empirically supported treatment strategies for use in a mutual help framework with in-person meetings, online meetings, a forum, and other resources.

To evaluate the effectiveness of OA and SMART Recovery (SR) with problem drinkers who were new to SMART Recovery. Our experimental hypotheses were: (1) all groups will reduce their drinking and alcohol/drug-related consequences at follow-up compared to their baseline levels, (2) the OA condition will reduce their drinking and alcohol/drug-related consequences more than the control group (SR), and (3) the OA+SR condition will reduce their drinking and alcohol/drug-related consequences more than the control group (SR only).

We recruited 189 heavy problem drinkers primarily through SMART Recovery’s website and in-person meetings throughout the United States. We randomly assigned participants to (1) OA alone, (2) OA+attend SMART Recovery (SR) meetings (OA+SR), or (3) attend SR only. Baseline and follow-ups were conducted via GoToMeeting sessions with a Research Assistant (RA) and the study participant. We interviewed significant others to corroborate the participant’s self-report. Primary outcome measures included percent days abstinent (PDA), mean drinks per drinking day (DDD), and alcohol/drug-related consequences.

The intent-to-treat analysis of the 3-month outcomes supported the first hypothesis but not the others. Participants in all groups significantly increased their percent days abstinent from 44% to 72% (P<.001), decreased their mean drinks per drinking day from 8.0 to 4.6 (P<.001), and decreased their alcohol/drug-related problems (P<.001). Actual use relationships were found for the OA groups, between SR online meetings and improvement in PDA (r=.261, P=.033). In addition in the OA groups, the number of total sessions of support (including SR & other meetings, counselor visits) was significantly related to PDA (r=.306, P=012) and amount of improvement in alcohol-related problems (r=.305, P=.012). In the SR only group, the number of face-to-face meetings was significantly related to all three dependent variables, and predicted increased PDA (r=.358, P=.003), fewer mean DDD (r=-.250, P=.039), and fewer alcohol-related problems (r=-.244, P=.045), as well as to the amount of improvement in all three of these variables. Six-month follow-ups have been completed, and the results are currently being analyzed.

These results support our first experimental hypothesis but not the second or third. All groups significantly increased their PDA and decreased both their mean DDD and their alcohol-related problems, which indicates that both interventions being investigated were equally effective in helping people recover from their problem drinking.



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NIH study identifies brain circuits involved in learning and decision making

Finding has implications for alcoholism and other patterns of addictive behavior

Research from the National Institutes of Health has identified neural circuits in mice that are involved in the ability to learn and alter behaviors. The findings help to explain the brain processes that govern choice and the ability to adapt behavior based on the end results.

Researchers think this might provide insight into patterns of compulsive behavior such as alcoholism and other addictions.

“Much remains to be understood about exactly how the brain strikes the balance between learning a behavioral response that is consistently rewarded, versus retaining the flexibility to switch to a new, better response,” said Kenneth R. Warren, Ph.D., acting director of the National Institute on Alcohol Abuse and Alcoholism. “These findings give new insight into the process and how it can go awry.”

The study, published online in Nature Neuroscience, indicates that specific circuits in the forebrain play a critical role in choice and adaptive learning.  > > > >  Read More

Critique 116: Effects of genetic factors on metabolism of alcohol — 10 July 2013

Forum Comments

This paper presents an excellent summary of the effects of genetically determined enzymes that affect the metabolism of alcohol; such factors relate strongly to both the rewarding and the aversive effects of alcohol. Of almost 100 genes that have been found to relate to alcohol metabolism, the two major ones appear to be alcohol dehydrogenase and aldehyde dehydrogenase. The authors describe the metabolism of alcohol into acetaldehyde by alcohol dehydrogenase, and then focus especially on the metabolism of acetaldehyde by aldehyde dehydrogenase-2.

Previous studies have shown that 20-40% of individuals of East Asian origin have a point mutation in the genes that code for high affinity aldehyde dehydrogenase-2; such people tend to show high levels of acetaldehyde and develop flushing, tachycardia, headache, nausea, and emesis from even small amounts of alcohol. Being very intolerant of alcohol, they are at very low risk of alcohol abuse. This mutation is much less common among European and North American populations.  > > > >   Read More

Readiness to change and brain damage in patients with chronic alcoholism

High motivation to change is a crucial triggering factor to patients’ engagement in clinical treatment.

This study investigates whether the low readiness to change observed in some alcoholic inpatients at treatment entry could, at least partially, be linked with macrostructural gray matter abnormalities in critical brain regions.

Participants comprised 31 alcoholic patients and 27 controls, who underwent 1.5-T magnetic resonance imaging. The Readiness to Change Questionnaire, designed to assess three stages of motivation to change (precontemplation, contemplation and action stages), was completed by all patients, who were then divided into “Action” (i.e. patients in action stage) and “PreAction” (i.e. patients in precontemplation or in contemplation stage) subgroups.

The PreAction subgroup, but not the Action subgroup, had gray matter volume deficits compared with controls. Unlike the patients in the Action subgroup, the PreAction patients had gray matter abnormalities in the cerebellum (Crus I), fusiform gyri and frontal cortex.

The low level of motivation to modify drinking behavior observed in some alcoholic patients at treatment entry may be related to macrostructural brain abnormalities in regions subtending cognitive, emotional and social abilities.

These brain volume deficits may result in impairment of critical abilities such as decision making, executive functions and social cognition skills. Those abilities may be needed to resolve ambivalence toward alcohol addiction and to apply “processes of change”, which are essential for activating the desire to change problematic behavior.


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Request Reprint E-Mail:     helene.beaunieux@unicaen.fr

Alcohol Consumption, Types of Alcohol, and Parkinson’s Disease

The epidemiologic evidence on alcohol consumption and Parkinson’s disease (PD) is equivocal. We prospectively examined total alcohol consumption and consumption of specific types of alcoholic beverage in relation to future risk of PD.

The study comprised 306,895 participants (180,235 male and 126,660 female) ages 50–71 years in 1995–1996 from the NIH-AARP Diet and Health Study. Consumption of alcoholic beverages in the past 12 months was assessed in 1995–1996. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained from logistic regression models.

A total of 1,113 PD cases diagnosed between 2000 and 2006 were included in the analysis. Total alcohol consumption was not associated with PD. However, the association differed by types of alcoholic beverages. Compared with non-beer drinkers, the multivariate ORs for beer drinkers were 0.79 for less than 1 drink/day, 0.73 for 1–1.99 drinks/day, and 0.86  for greater or equal drinks/day. For liquor consumption, a monotonic increase in PD risk was suggested: ORs  were 1.06 .22 , and 1.35  for less than 1, 1–1.99, and ≥2 drinks/day, respectively. Additional analyses among exclusive drinkers of one specific type of alcoholic beverage supported the robustness of these findings. The results for wine consumption were less clear, although a borderline lower PD risk was observed when comparing wine drinkers of 1–1.99 drinks/day with none drinkers .

Our results suggest that beer and liquor consumption may have opposite associations with PD: low to moderate beer consumption with lower PD risk and greater liquor consumption with higher risk. These findings and potential underlying mechanisms warrant further investigations.


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Ectopic hippocampal neurogenesis in adolescent male rats following alcohol dependence

The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function.

Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence.

Thus, we examined neurogenesis in adolescent male rats during abstinence following a 4-day binge model of alcohol dependence.

Bromodeoxyuridine and Ki67 immunohistochemistry revealed a 2.2-fold increase in subgranular zone cell proliferation after 7 days of abstinence. Increased proliferation was followed by a 75% increase in doublecortin expression and a 56% increase in surviving bromodeoxyuridine-labeled cells 14 and 35 days post-ethanol exposure, respectively.

The majority of newborn cells in ethanol and control groups co-localized with NeuN, indicating a neuronal phenotype and therefore a 1.6-fold increase in hippocampal neurogenesis during abstinence.

Although these results mirror the magnitude of reactive
neurogenesis described in adult rat studies, ectopic bromodeoxyuridine and doublecortin positive cells were detected in the molecular layer and hilus of adolescent rats displaying severe withdrawal symptoms, an effect that has not been described in adults.

The presence of ectopic neuroblasts suggests that a potential defect exists in the functional incorporation of new neurons into the existing hippocampal circuitry for a subset of rats.

Age-related differences in functional incorporation could contribute to the increased vulnerability of the adolescent hippocampus to ethanol.



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Request Reprint E-Mail:     kim-nixon@uky.edu