To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.


Saturday, September 14, 2013

Childhood Verbal Development and Drinking Behaviors from Adolescence to Young Adulthood: A Discordant Twin-Pair Analysis

Studies suggest that better cognitive and verbal abilities in childhood predict earlier experimentation with alcohol and higher levels of drinking in adolescence, whereas poorer ability is related to a higher likelihood of remaining abstinent. Whether individual differences in language development in childhood predict differences in adolescent drinking behaviors has not been studied.
To address that question, we compared co-twins from twin pairs discordant for their childhood language development and studied associations of parental reports of within-pair differences in age at speaking words, age at learning to read, and expressive language skills during school age with self-reported within-pair differences in drinking, intoxication, and alcohol-related problems across adolescence and young adulthood. Data from 2 longitudinal population-based samples of twin families were used, with verbal developmental differences in childhood reported by the parents when the twins were 12 and 16 years of age, respectively.
Conditional logistic regression analyses and within-pair correlation analyses suggested positive associations between verbal development and drinking behaviors in both data sets. In analyses adjusted for birth order and birth weight, the co-twin reported to be verbally more advanced in childhood tended to report more frequent drinking and intoxication in adolescence in both samples. Better verbal development also was associated with the likelihood of having friends who drink in adolescence.
These findings suggest that, adjusting for familial and other factors shared by co-twins, better verbal development in childhood predicts more frequent drinking and intoxication in adolescence and young adulthood, possibly due, in part, to peer associations.

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Perceived Danger While Intoxicated Uniquely Contributes to Driving After Drinking

Previous findings suggest that alcohol alters perceptions of risky behaviors such as drinking and driving. However, studies testing these perceptions as a predictor of drinking and driving typically measure these perceptions while participants are sober. This study tested whether the perceived danger of driving after drinking assessed while intoxicated was associated with increased willingness to drive and self-reported drinking-and-driving behavior over and above perceptions assessed while sober. Additionally, we tested the effect of acute tolerance on the perceived danger of driving after drinking assessed on the ascending and descending limbs of the breath alcohol concentration (BrAC) curve.
Eighty-two young adults attended 2 counterbalanced laboratory sessions. In one session, participants consumed a moderate dose of alcohol (men: 0.72 g/kg, women: 0.65 g/kg) and reported their perceived danger of driving and willingness to drive at multiple points across the BrAC curve. On a separate occasion, participants remained sober and appraised the dangerousness of driving at a hypothetical, illegal BrAC.
Perceptions of the dangerousness of driving following alcohol administration were associated with increased willingness to drive and higher rates of self-reported drinking-and-driving behavior over and above perceptions reported when sober. Furthermore, perceived danger was reduced on the descending limb of the BrAC curve, compared with the ascending limb, suggesting the occurrence of acute tolerance.
Results from this study suggest that intoxicated perceptions are uniquely associated with drinking-and-driving decisions and that the perceived danger of drinking and driving is lower on the descending limb of the BrAC curve. Efforts to prevent alcohol-impaired driving have focused on increasing awareness of the danger of driving after drinking. Prevention efforts may be enhanced by educating drivers about how intoxication can alter perceived danger, and interventions may benefit from targeting perceptions of dangerousness while individuals are intoxicated in addition to when they are sober.

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Psychiatric Comorbidity and 12-Step Participation: A Longitudinal Investigation of Treated Young Adults

Evidence indicates that 12-step mutual-help organizations (MHOs), such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA), can play an important role in extending and potentiating the recovery benefits of professionally delivered addiction treatment among young adults with substance use disorders (SUD). However, concerns have lingered regarding the suitability of 12-step organizations for certain clinical subgroups, such as those with dual diagnosis (DD). This study examined the influence of diagnostic status (DD vs. SUD-only) on both attendance and active involvement (e.g., having a sponsor, verbal participation during meetings) in, and derived benefits from, 12-step MHOs following residential treatment.
Young adults (N = 296; 18 to 24 years old; 26% female; 95% Caucasian; 47% DD [based on structured diagnostic interview]), enrolled in a prospective naturalistic study of SUD treatment effectiveness, were assessed at intake and 3, 6, and 12 months posttreatment on 12-step attendance/active involvement and percent days abstinent (PDA). t-Tests and lagged, hierarchical linear models (HLM) examined the extent to which diagnostic status influenced 12-step participation and any derived benefits, respectively.

For DD and SUD-only patients, posttreatment attendance and active involvement in 12-step
organizations were similarly high. Overall, DD patients had significantly lower PDA relative to SUD-only patients. All patients appeared to benefit significantly from attendance and active involvement on a combined 8-item index. Regarding the primary effects of interest, significant differences did not emerge in derived benefit between DD and SUD-only patients for either attendance (p = 0.436) or active involvement (p = 0.062). Subsidiary analyses showed, however, that DD patients experienced significantly greater abstinence-related benefit from having a 12-step sponsor.
Despite concerns regarding the clinical utility of 12-step MHOs for DD patients, findings indicate that DD young adults participate and benefit as much as SUD-only patients, and may benefit more from high levels of active involvement, particularly having a 12-step sponsor. Future work is needed to clarify how active 12-step involvement might offset the additional recovery burden of a comorbid mental illness on substance use outcomes.

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Does the Severity of Hangovers Decline with Age? Survey of the Incidence of Hangover in Different Age Groups

Alcohol hangover is a growing research area, but differences across the life span have not been assessed. Here, we test the hypothesis that the severity of hangovers depends on age.
A cross-sectional study of 51,645 men and women aged 18 to 94 years old, who participated in the population-based Danish Health Examination Study (DANHES) in Denmark between 2007 and 2008, formed the database for our study.
The incidence of severe hangover was lower among older than younger participants. Odds ratios for experiencing severe hangover following an episode of binge drinking were 6.8, 4.8, 3.0, and 2.0 among the 18 to 29, 30 to 39, 40 to 49, and 50 to 59-year-old men, compared with those aged 60+ years. For women, similar results were obtained. This finding could not be explained by the usual amount of alcohol consumption, frequency of binge drinking, or the proportion of alcohol consumed with meals.
We found that hangover following engagement in binge drinking is much more common in the young than in the older age groups.

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Friday, September 13, 2013

Energy drinks and alcohol: research supported by industry may be downplaying harms

Concern is growing about the harms that may arise from heavy drinkers mixing alcohol with so called energy drinks to enable them to drink for longer and achieve higher levels of intoxication. On Friday and Saturday evenings, about 40% of people on Australian city streets are heavily intoxicated (breath alcohol concentrations (BAC) greater than 0.087 mg alcohol/100 ml) and nearly a quarter of these drinkers will have consumed more than two energy drinks.1 Data are lacking on energy drink use by alcohol drinkers in other countries but in samples, 73% of US college students2 and 85% of Italian college students3 reported consuming energy drinks mixed with alcohol in the past month.

Epidemiological studies show that drinkers who consume energy drinks are more likely to record a higher breath alcohol concentration than those who do not.4 They are also more likely to report drinking more alcohol5; engaging in aggressive acts1; being injured1 6; symptoms of alcohol dependence7; having driven while drunk or been a passenger in a car with an alcohol impaired driver1; and having taken sexual advantage of, or having been taken advantage of, by another person.

The role that energy drinks may play in facilitating intoxication is under-researched. Because of ethical concerns about people getting too drunk and drinking too many energy drinks, much of the research in laboratory settings has studied only the effects of combining low levels of alcohol intoxication (BAC less than 0.1 mg alcohol/100 ml) with a single energy drink (equivalent to a strong cup of coffee).

Some researchers doing these studies have concluded that we should not be concerned about the risks of combining alcohol and energy drinks. But evidence from these studies does not convincingly refute the hypothesis that more energy drinks consumed with more alcohol facilitates intoxication and increases the risk of alcohol related injuries and assaults.
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Thursday, September 12, 2013

Alcohol stress response dampening during imminent versus distal, uncertain threat.

Research indicates that fear and anxiety are distinct processes with separable neurobiological substrates. Predictable versus unpredictable shock administration has been used to elicit fear versus anxiety, respectively. Recent research has demonstrated that alcohol may reduce anxiety but not fear. However, previous manipulations of predictability have varied both probability and temporal uncertainty of shock threat, leaving unresolved questions regarding which stimulus characteristics elicit anxiety and are sensitive to alcohol stress-response dampening (SRD).

We developed a novel paradigm to closely parallel basic research in animals that systematically varied temporal uncertainty of threat while holding threat probability constant. Intoxicated (0.08% target blood alcohol concentration), placebo, and no-alcohol control participants viewed a series of visual threat cues. Certain cue duration (5 s) blocks were equivalent to predictable shock blocks eliciting fear in earlier research. Uncertain cue duration (5, 20, 50, or 80 s, intermixed) blocks introduced temporal uncertainty regarding impending shock to elicit anxiety. Startle potentiation relative to matched cue periods in no-shock blocks provided the primary measure of affective response. All threat cues produced robust startle potentiation.

Alcohol reduced startle potentiation during the first 5 s of threat cue presentation in uncertain but not certain duration blocks. Alcohol also reduced startle potentiation at later times among longer uncertain duration cues, suggesting that alcohol SRD persisted. Trait negative emotionality and binge drinking status moderated alcohol SRD magnitude during uncertain threat.

These translational findings corroborate previous reports regarding distinct substrates of fear versus anxiety and have implications for both alcoholism etiology and comorbidity with anxiety disorders.

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The effect of alcohol on emotional inertia: A test of alcohol myopia.

Alcohol myopia (AM) has emerged as one of the most widely researched theories of alcohol’s effects on emotional experience. Given this theory’s popularity, it is notable that a central tenet of AM has not been tested—namely, that alcohol creates a myopic focus on the present moment, limiting the extent to which the present is permeated by emotions derived from prior experience.

We tested the impact of alcohol on moment-to-moment fluctuations in affect, applying advances in emotion assessment and statistical analysis to test this aspect of AM without drawing the attention of participants to their own emotional experiences. We measured emotional fluctuations using autocorrelation, a statistic borrowed from time-series analysis measuring the correlation between successive observations in time. High emotion autocorrelation is termed emotional inertia and is linked to negative mood outcomes. Social drinkers (N = 720) consumed alcohol, placebo, or control beverages in groups of 3 over a 36-min group formation task. We indexed affect using the Duchenne smile, recorded continuously during the interaction (34.9 million video frames) according to the Facial Action Coding System (P. Ekman, W. V. Friesen, & J. C. Hager, 2002).

Autocorrelation of Duchenne smiling emerged as the most consistent predictor of self-reported mood and social bonding when compared with Duchenne smiling mean, standard deviation, and linear trend. Alcohol reduced affective autocorrelation, and autocorrelation mediated the link between alcohol and self-reported mood and social outcomes.

Findings suggest that alcohol enhances the ability to freely enjoy the present moment untethered by past experience and highlight the importance of emotion dynamics in research examining affective correlates of psychopathology.

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The triangular association of ADH1B genetic polymorphism, alcohol consumption and the risk of depression in older men

Alcohol use, particularly alcohol abuse and dependence, are associated with increased risk of depression. Current diagnostic criteria suggest that the relationship is causal, but the evidence has only been derived from observational studies that are subject to confounding and bias.

Given the logistic and ethical constraints that would be associated with a trial of alcohol use to prevent depression, we aimed to complete a Mendelian randomization study to determine if a genetic polymorphism associated with alcohol abuse and dependence (ADH1B rs1229984 G
A) contributed to modulate the risk of depression in a community-derived cohort of older men.

This retrospective analysis of a cohort of 3873 community-dwelling men aged 65–83 years living in the metropolitan region of Perth, Western Australia, investigated the triangular association between the rs1229984 GA polymorphism and alcohol use and, after 3.2–8.2 years, the presence of current depression or history of depression. The mean number of standard drinks consumed per week (n; standard deviation; range) according to genotype was AA 1.8 (17; 2.7; 0–7), GA 5.9 (262; 7.5; 0–35), GG 8.5 (3594; 10.9; 0–140) (GG>AA, GG>GA;) .

Consumption of 1 or 2 drinks per day decreased the odds of depression
(n=610) by 30 and 40%, whereas consumption of more than six drinks daily more than doubled the odds of depression (odds ratio: 2.12, 95% confidence interval: 1.02, 4.40). The ADH1B rs1229984 GA polymorphism was not associated with current or past depression (P=0.857). In addition, the presence of the A allele did not interact with the alcohol use to modulate the risk of depression (P=0.725).

These results suggest that alcohol consumption does not cause or prevent depression in older men.

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Global Actions: Commitments to Reduce Harmful Drinking. Sep 12, 2013

Global Actions in Focus
“Responsible drinking: don’t drink and drive”
Commercial driver training program
In partnership with the Institute of Road Traffic Education and College of Traffic Management (IRTE), Global Actions India held a series of training seminars, “Responsible Drinking: Don’t Drink and Drive,” to educate commercial drivers about responsible drinking and the consequences of drink driving. IRTE launched the seminars in April 2013 and will continue to run the training program through December 2013. The initiative targets Delhi commercial drivers, including bus, truck, and auto rickshaw drivers, and all training sessions are held at the Driver Training Center of IRTE in Okhla, New Delhi. From April 22 to August 31, a total of 4,745 drivers completed the training course.

During the first seminar in April, feedback from the participants was collected manually. After evaluating this method of data collection, the program transitioned to collecting feedback and suggestions from participating commercial drivers through a software application both before and after the training was completed. The survey questions, which are presented both in Hindi and English, are now displayed on an LED monitor. Instructors lead the participants through each question in the survey, and the drivers are able to choose their answer through a remote control. The software allows IRTE to test up to 25 drivers at one time, providing a faster and more efficient testing process that also allows semi-illiterate individuals to offer feedback on the training program.

From August 21 to 31, 345 drivers completed the drink driving training modules and also provided survey response about their driving behavior. While 339 drivers believed that consuming beverage alcohol before operating a vehicle would increase their risk of causing a road traffic crash, 150 of the respondents admitted to drink driving while operating a commercial vehicle. Out of the respondents, 221 said they had been a passenger of a motor vehicle being operated by someone who had consumed alcohol.
Among the program participants who have completed the electronic survey since May, 79% found the information presented during the training very useful and 94% believed the workshop should be integrated into existing defensive driving training programs. For more than two-thirds of the drivers, the “Responsible Drinking: Don’t Drink and Drive” seminar was the first training program on drink driving they had attended
Key Recent Milestones
· Worldwide: Global Actions Facebook page had 20,200 impressions in July and August and the ICAP Facebook page had 18,200 impressions during the same time frame.

What's Happening Next
· Vietnam: The launch of Phase Two of the Drink Driving Initiative in Da Nang, Vietnam will take place on September 18, 2013. Following the event, the International Center for Alcohol Policies and Pernod Ricard are hosting a responsible drinking workshop for 500 Da Nang University students.

Tailoring a response to youth binge drinking in an Aboriginal Australian community: a grounded theory study

While Aboriginal Australian health providers prioritise identification of local community health needs and strategies, they do not always have the opportunity to access or interpret evidence-based literature to inform health improvement innovations. Research partnerships are therefore important when designing or modifying Aboriginal Australian health improvement initiatives and their evaluation. However, there are few models that outline the pragmatic steps by which research partners negotiate to develop, implement and evaluate community-based initiatives. The objective of this paper is to provide a theoretical model of the tailoring of health improvement initiatives by Aboriginal community-based service providers and partner university researchers. It draws from the case of the Beat da Binge community-initiated youth binge drinking harm reduction project in Yarrabah.     
A theoretical model was developed using the constructivist grounded theory methods of concurrent sampling, data collection and analysis. Data was obtained from the recordings of reflective Community-Based Participatory Research (CBPR) processes with Aboriginal community partners and young people, and university researchers. CBPR data was supplemented with interviews with theoretically sampled project participants. The transcripts of CBPR recordings and interviews were imported into NVIVO and coded to identify categories and theoretical constructs. The identified categories were then developed into higher order concepts and the relationships between concepts identified until the central purpose of those involved in the project and the core process that facilitated that purpose were identified.     
The tailored alcohol harm reduction project resulted in clarification of the underlying local determinants of binge drinking, and a shift in the project design from a social marketing awareness campaign (based on short-term events) to a more robust advocacy for youth mentoring into education, employment and training. The community-based process undertaken by the research partnership to tailor the design, implementation and evaluation of the project was theorised as a model incorporating four overlapping stages of negotiating knowledges and meanings to tailor a community response.  
The theoretical model can be applied in spaces where local Aboriginal and scientific knowledges meet to support the tailored design, implementation and evaluation of other health improvement projects, particularly those that originate from Aboriginal communities themselves.
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Wednesday, September 11, 2013

RCPI Alcohol Policy Group Pre-Budget Submission 2014

The Royal College of Physicians of Ireland's Alcohol Policy Group bas called for the introduction of minimum pricing and an increase in excise duty in its Pre-Budget Submission 2014.

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Brief intervention and decrease of alcohol consumption among women: a systematic review

Problems related to alcohol consumption are priority public health issues worldwide and may compromise women's health. The early detection of risky alcohol consumption combined with a brief intervention (BI) has shown promising results in prevention for different populations.

The aim of this study was to examine data from recent scientific publications on the use of BI toward reducing alcohol consumption among women through a systematic review. Electronic searches were conducted using Web of Science, PubMed(Medline) and PsycInfo databases. In all databases, the term "brief intervention" was associated with the words "alcohol" and "women", and studies published between the years 2006 and 2011 were selected. Out of the 133 publications found, the 36 scientific articles whose central theme was performing and/or evaluating the effectiveness of BI were included. The full texts were reviewed by content analysis technique.
This review identified promising results of BI for women, especially pregnant women and female college students, in different forms of application (face-to-face, by computer or telephone) despite a substantial heterogeneity in the clinical trials analyzed. In primary care, which is a setting involving quite different characteristics, the results among women were rather unclear.

In general, the results indicated a decrease in alcohol consumption among women following BI, both in the number of days of consumption and the number of doses, suggesting that the impact on the woman's reproductive health and the lower social acceptance of female consumption can be aspects favorable for the effectiveness of BI in this population.

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Transdermal Delivery of Cannabidiol Attenuates Binge Alcohol-Induced Neurodegeneration in a Rodent Model of an Alcohol Use Disorder

Excessive alcohol consumption, characteristic of alcohol use disorders, results in neurodegeneration and behavioral and cognitive impairments that are hypothesized to contribute to the chronic and relapsing nature of alcoholism.

Therefore, the current study aimed to advance the preclinical development of transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced neurodegeneration.

In experiment 1, 1.0%, 2.5% and 5.0% CBD gels were evaluated for neuroprotection. The 5.0% CBD gel resulted in a 48.8% reduction in neurodegeneration in the entorhinal cortex assessed by Fluoro-Jade B (FJB), which trended to statistical significance ( p = 0.069). Treatment with the 5.0% CBD gel resulted in day 3 CBD plasma concentrations of ~ 100.0 ng/mL so this level was used as a target concentration for development of an optimized gel formulation.

Experiment 2 tested a next generation 2.5% CBD gel formulation, which was compared to CBD administration by intraperitoneal injection (IP; 40.0 mg/kg/d). This experiment found similar magnitudes of neuroprotection following both routes of administration; transdermal CBD decreased FJB + cells in the entorhinal cortex by 56.1% (p < 0.05), while IP CBD resulted in a 50.6% (p < 0.05) reduction in FJB + cells.
These results demonstrate the feasibility of using CBD transdermal delivery systems for the treatment of alcohol-induced neurodegeneration.

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Tuesday, September 10, 2013

Association Between Maternal Alcohol Consumption in Early Pregnancy and Pregnancy Outcomes

To investigate the association between alcohol consumption and binge drinking before and during early pregnancy and adverse pregnancy outcomes.

We used data from 5,628 nulliparous pregnant participants recruited to the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study. Participants were interviewed at 15 weeks of gestation and information on alcohol intake before pregnancy and until the time of interview was obtained using a standardized questionnaire. Alcohol intake was classified as occasional (1-2 units per week), low (3-7 units per week), moderate (8-14 units per week), and heavy (greater than 14 units per week). Binge alcohol consumption was defined as consumption of 6 or more alcohol units in one session.

Of the 5,628 participants, 1,090 (19%) reported occasional alcohol consumption, 1,383 (25%) low alcohol consumption, 625 (11%) moderate alcohol consumption, and 300 (5%) heavy alcohol consumption. Overall, 1,905 (34%) participants reported binge alcohol consumption in the 3 months before pregnancy, and 1,288 (23%) of these participants reported binge alcohol consumption during the first 15 weeks of pregnancy. Participants who consumed occasional to heavy amounts of alcohol in early pregnancy did not have altered odds of a small-for-gestational-age neonate, reduced birth weight, preeclampsia, or spontaneous preterm birth. Similarly, those who binge drank in early pregnancy did not have altered odds of these adverse pregnancy outcomes.

Alcohol consumption in early pregnancy was prevalent in this nulliparous cohort. There was no association between alcohol consumption before 15 weeks of gestation and small for gestational age, reduced birth weight, preeclampsia, or spontaneous preterm birth.

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Do Importance of Religious Faith and Healthy Lifestyle Modify the Relationships Between Depressive Symptoms and Four Indicators of Alcohol Consumption? A Survey of Students Across Seven Universities in England, Wales, and Northern Ireland

We examined the associations between depressive symptoms and four indicators of alcohol consumption (high frequency of drinking, frequency of heavy episodic drinking, problem drinking, and possible alcohol dependence). We also explored whether personal importance of religious faith as well as healthy lifestyle had any modifying roles in these relationships.
During 2007–2008, 3,220 students at seven UK universities completed a questionnaire containing questions on CAGE, frequency alcohol use, heavy episodic drinking, modified Beck-Depression Inventory, physical activity and sleep, and importance of religious faith. Multivariate logistic regressions were performed separately for four alcohol consumption indicators, stratified by gender.
Controlling for demographic variables, depressive symptoms were positively associated with problem drinking and possible alcohol dependence for both genders. Religiosity was negatively associated with frequency of drinking and heavy episodic drinking among both genders, while healthy lifestyle was not associated with any of the four measures of alcohol consumption among both genders.
No evidence suggested that either religiosity or healthy lifestyle modified the relationships between depressive symptoms and any of the four measures of alcohol consumption.

This study shows a link between hazardous drinking and mental ill health and suggests religiosity as a protective factor for high alcohol consumption. Promotion of students’ mental and spiritual health could have a preventive role in hazardous drinking at universities.


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News Release - Nearly 18 percent of pregnant women drink alcohol in early stages of pregnancy

Approximately 18 percent of women in their first trimester of pregnancy used alcohol within the past month according to a new report by the Substance Abuse and Mental Health Services Administration (SAMHSA). The report showed that 6.6 percent of women in their first trimester of pregnancy engaged in binge drinking (i.e., drinking five or more drinks on the same occasion at least once in the past 30 days). 
Women who drink alcohol while pregnant increase their infants’ risk of developing a Fetal Alcohol Spectrum Disorder (FASD), a group of conditions that can cause physical, behavioral and learning problems – some of which may have lifelong repercussions. Although there is no safe amount of alcohol for pregnant women to drink, they can lower the risk for their infants when they stop drinking alcohol immediately after finding out they are pregnant.
The report indicates that the level of alcohol use dropped sharply among pregnant woman in their second and third trimesters. The rate of past month alcohol use (i.e., at least one drink in the past 30 days) for women in the second trimester of pregnancy fell to 4.2 percent and among women in the third trimester dipped to 3.7 percent. By comparison, 55.5 percent of non-pregnant women aged 15 to 44 consumed alcohol in the past month.  > > > >  Read More

BRSS TACS Webinar Series: Recovery-Oriented Practice- Person/Family-Centered Recovery Planning


This FREE SAMHSA webcast will air on Thursday, September 12, 2013 at 1:00 - 2:30 ET (12:00 CT, 11:00 MT, 10:00 PT). This webinar will seek to accomplish the following objectives:
  • Present an overview of person/family-centered planning
  • Describe models of person/family-centered planning for people with mental and/or substance use disorders
  • Discuss the range of services and supports that people and their families want to have available to them as they strive to accomplish their goals
  • Discuss peer/parent support roles within each model
All BRSS TACS webinars are recorded, closed captioned, and available for viewing at your convenience. Visit the BRSS TACS webinars page to access the archived webinars.
Register for the Webinar

Family-Based Association Analysis of Alcohol Dependence Criteria and Severity

Despite the high heritability of alcohol dependence (AD), the genes found to be associated with it account for only a small proportion of its total variability. The goal of this study was to identify and analyze phenotypes based on homogeneous classes of individuals to increase the power to detect genetic risk factors contributing to the risk of AD.

The 7 individual DSM-IV criteria for AD were analyzed using latent class analysis (LCA) to identify classes defined by the pattern of endorsement of the criteria. A genome-wide association study was performed in 118 extended European American families (n = 2,322 individuals) densely affected with AD to identify genes associated with AD, with each of the 7 DSM-IV criteria, and with the probability of belonging to 2 of 3 latent classes.


Heritability for DSM-IV AD was 61% and ranged from 17 to 60% for the other phenotypes. A single nucleotide polymorphism (SNP) in the olfactory receptor OR51L1 was significantly associated (7.3 × 10−8) with the DSM-IV criterion of persistent desire to, or inability to, cut down on drinking. LCA revealed a 3-class model: the “low-risk” class (50%) rarely endorsed any criteria and none met criteria for AD; the “moderate-risk” class (33%) endorsed primarily 4 DSM-IV criteria and 48% met criteria for AD; and the “high-risk” class (17%) manifested high endorsement probabilities for most criteria and nearly all (99%) met criteria for AD. One SNP in a sodium leak channel NALCN demonstrated genome-wide significance with the high-risk class (p = 4.1 × 10−8). Analyses in an independent sample did not replicate these associations.

We explored the genetic contribution to several phenotypes derived from the DSM-IV AD criteria. The strongest evidence of association was with SNPs in NALCN and OR51L1.

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