The Impact of Alcohol Use on Frontal White Matter in HIV.

BACKGROUND: Alcohol use disorder (AUD) is prevalent among individuals diagnosed with human immunodeficiency virus (HIV), and both HIV and alcohol use have been shown to negatively affect the integrity of white matter pathways in the brain. Behavioral, functional, and anatomical impairments have been linked independently to HIV and alcohol use, and these impairments have bases in specific frontally mediated pathways within the brain. METHODS: Magnetic resonance imaging data were acquired for 37 HIV+ participants without dementia or hepatitis C. Imaging data were processed through the FreeSurfer and TraCULA pipelines to obtain 4 bilateral frontal white matter tracts for each participant. Diffusion metrics of white matter integrity along the highest probability pathway for each tract were analyzed with respect to demographics, disease-specific variables, and reported substance use. RESULTS: Significantly increased axial diffusivity (decreased axonal integrity) and a trending increase in mean diffusivity were observed along the anterior thalamic radiation (ATR) in participants with a history of AUD. A diagnosis of AUD explained over 36% of the variance in diffusivity along the ATR overall when accounting for clinical variables including nadir CD4 and age-adjusted HIV infection length. CONCLUSIONS: This study provides evidence of HIV-related associations between alcohol use and indicators of axonal integrity loss along the ATR, a frontal pathway involved in the inhibition of addictive or unwanted behaviors. Reduced axonal integrity of this pathway was greatest in HIV+ participants with an AUD, even when considering the effect of age-adjusted disease length and severity (nadir CD4). This finding implicates a potential biological mechanism linking reduced integrity of frontal white matter to the high prevalence of AUD in an HIV+ population without dementia or hepatitis C.

Liver Injury and Endotoxemia in Male and Female Alcohol-Dependent Individuals Admitted to an Alcohol Treatment Program.

BACKGROUND: Interactions between the liver, the gut, and the immune system are critical components of alcoholic liver disease (ALD). The aim of this study was to explore the associations between alcohol-induced liver injury, endotoxemia, and inflammation at admission and over time during abstinence, as well as to examine the sex-related differences in these parameters in alcohol-dependent individuals admitted to an alcohol treatment program. METHODS: A cohort of 48 otherwise healthy participants with alcohol use disorder, but no clinical signs of alcoholic liver injury (34 males [M]/14 females [F]) admitted to an alcohol detoxification program, was stratified into 2 groups based on baseline plasma alanine aminotransferase (ALT) levels (as a marker of liver injury). Group 1 (ALT < 40 U/l, 7M/8F) and Group 2 (ALT ≥ 40 U/l, 27M/6F) were identified. Plasma biomarkers of liver damage, endotoxemia, and inflammation were examined at baseline, day 8, and day 15 of the admission. The drinking history was also evaluated. RESULTS: Sixty-nine percent of patients had elevated ALT and other markers of liver damage, including aspartate aminotransferase and cytokeratin 18 (CK18 M65 and CK M30) at baseline, indicating the presence of mild ALD. Elevated CK18 M65:M30 ratio suggested a greater contribution of necrotic rather than apoptotic hepatocyte cell death in the liver injury observed in these individuals. Females showed greater elevations of liver injury markers compared to males, although they had fewer drinks per day and shorter lifetime duration of heavy drinking. Liver injury was associated with systemic inflammation, specifically, elevated plasma tumor necrosis factor-alpha levels. Compared to patients without liver injury, patients with mild ALD had greater endotoxemia (increased serum lipopolysaccharide levels), which decreased with abstinence and this decrease preceded the drop in CK18 M65 levels. CONCLUSIONS: The study documented the association of mild alcohol-induced liver injury and endotoxemia, which improved with 2 weeks of abstinence, in a subset of individuals admitted to an alcohol detoxification program.

Clinical impact of alcohol-related cirrhosis in the next decade: estimates based on current epidemiological trends in the United States.

BACKGROUND: Identifying changes in the epidemiology of liver disease is critical for establishing healthcare priorities and allocating resources to develop therapies. The projected contribution of different etiologies toward development of cirrhosis in the United States was estimated based on current publications on epidemiological data and advances in therapy. Given the heterogeneity of published reports and the different perceptions that are not always reconcilable, a critical overview rather than a formal meta-analysis of the existing data and projections for the next decade was performed. METHODS: Data from the World Health Organization Global Status Report on Alcohol and Health of 2014, Scientific Registry of Transplant Recipients from 1999 to 2012, National Institute on Alcohol Abuse and Alcoholism, and the Centers for Disease Control and Prevention were inquired to determine future changes in the epidemiology of liver disease. RESULTS: Alcohol consumption has increased over the past 60 years. In 2010, transplant-related costs for liver recipients were the highest for hepatitis C (~$124 million) followed by alcohol-related cirrhosis (~$86 million). We anticipate a significant reduction in incidence cirrhosis due to causes other than alcohol because of the availability of high efficiency antiviral agents for hepatitis C, universal and effective vaccination for hepatitis B, relative stabilization of the obesity trends in the United States, and novel, potentially effective therapies for nonalcoholic steatohepatitis. The proportion of alcohol-related liver disease is therefore likely to increase in both the population as a whole and the liver transplant wait list. CONCLUSIONS: Alcohol-related cirrhosis and alcohol-related liver disorders will be the major cause of liver disease in the coming decades. There is an urgent need to allocate resources aimed toward understanding the pathogenesis of the disease and its complications so that effective therapies can be developed.

The Utility of Including the Strengths of Underage Drinking Laws in Determining Their Effect on Outcomes.

BACKGROUND: To control underage drinking in the United States, which has been associated with an estimated 5,000 deaths and 2.6 million injuries or other harm annually, each state has developed a unique set of laws. Previous research examining these laws' effectiveness has frequently focused on the laws' existence without considering variance in sanctions, enforcement, or exemptions. METHODS: We scored 20 minimum legal drinking age 21 (MLDA-21) laws for their strengths and weaknesses based on (i) sanctions for violating the law, (ii) exceptions or exemptions affecting application, and (iii) provisions affecting the law or enforcement. We then replicated a 2009 study of the effects of 6 MLDA-21 laws in 3 different ways (using identical structural equation modeling): Study 1-8 additional years of data, no law strengths; Study 2-years from the original study, added law strengths; Study 3-additional years, law strengths, serving as an update of the 6 laws' effects. RESULTS: In all 3 studies-and the original study-keg registration laws were associated with both an unexpected significant increase (+11%, p < 0.001) in underage drinking-driver ratios and a notable 25% reduction in per capita beer consumption-opposing results that are difficult to explain. In Study 3, possession and purchase laws were associated with a significant decrease in underage drinking-driver fatal crash ratios (-4.9%, p < 0.001; -3.6%, p < 0.001, respectively). Similarly, zero tolerance and use and lose laws were associated with reductions in underage drinking-driver ratios (-2.8%, p < 0.001; -5.3%, p < 0.001, respectively). CONCLUSIONS: Including strengths and weaknesses of underage drinking laws is important when examining their effects on various outcomes as the model fit statistics indicated. We suggest that this will result in more accurate and more reliable estimates of the impact of the laws on various outcome measures.

Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism.

Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented.

DSM-IV alcohol dependence and marital dissolution: evidence from the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVE: The purpose of this study was to examine the cross-sectional and longitudinal associations among alcohol use disorder (AUD), stressful life events, and marital dissolution in a probability sample of adults. METHOD: The National Epidemiologic Survey on Alcohol and Related Conditions is a prospective, longitudinal study of a probability sample of 43,083 adults 18 years of age and older living in the United States. The interval between Wave 1 (W1) and Wave 2 (W2) was approximately 3 years. Cross-sectional analyses included 32,359 adults ages 18 and older who were ever married at W1, and longitudinal analyses included 17,192 adults who were currently married at W1 and who completed relevant W2 measures. Participants completed inhome surveys conducted with computer-assisted personal interviewing. RESULTS: Rates of lifetime marital dissolution were significantly higher among those with lifetime AUD (48.3%) than in those with no lifetime AUD (30.1%). The incidence of marital dissolution from W1 to W2 was 15.5% for those with a past-12-month AUD at W1, compared to 4.8% among those with no AUD. Proportional hazards regression analyses showed that past-12-month AUD, tobacco use disorder, other substance use disorder, stressful life events, older age at marriage, being married more than once, and being married to an alcoholic at W1 predicted greater hazards of marital dissolution at W2. These associations were not moderated by gender. CONCLUSIONS: AUD and stressful life events predict subsequent marital dissolution independently of other substance use disorders, mood and anxiety disorders, and personality disorders. Results were discussed within the framework of the Vulnerability-Stress-Adaptation model of marriage.

College student drinking research from the 1940s to the future: where we have been and where we are going.

OBJECTIVE: College student drinking is not a new phenomenon, yet the field of research studying college student drinking is relatively young. In recognition of the 75th anniversary of what is now the Journal of Studies on Alcohol and Drugs, this article reviews the path from the first article to focus exclusively on college student drinking as the topic (published in 1945) to the current state of the science and attempts to look forward to the next steps in the field's research agenda. METHOD: Articles were selected by consensus of the authors from incarnations of the journal and other academic journals based on their relevance to the genesis of current best practices regarding college student drinking prevention. RESULTS: Major eras and themes include (a) early efforts to describe and understand college student drinking; (b) building foundations for prevention and intervention efforts in response to growing concerns about high-risk drinking; (c) the emergence of harm-reduction efforts, normative interventions, and efforts to document campus strategies; (d) efficacious prevention efforts and high-risk drinking; (e) the "Call to Action" Task Force Report from the National Institute on Alcohol Abuse and Alcoholism; and (f) updates to the science (including emerging technology). CONCLUSIONS: Understanding the rich history of science related to college drinking prevention should prepare and guide our field for the next 75 years of scientific advances, leading to even greater understanding of the etiology and topology of college student drinking as well as more effective methods to reduce alcohol-related harms.

The prevalence of harmful and hazardous alcohol consumption in older U.S. adults: data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Alcohol consumption and its interaction with disease, medication use, and functional status may result in serious health problems, but little information exists about the national prevalence of alcohol-related health risk in older adults. OBJECTIVE: To estimate the prevalence of harmful and hazardous alcohol use and the prevalence of consumption in excess of National Institute of Alcohol Abuse and Alcoholism (NIAAA) recommendations, in people aged 65 and older, and by sex and race/ethnicity sub-group. DESIGN: Cross-sectional, using data from the 2005-2008 National Health and Nutrition Examination Survey of the non-institutionalized U.S. population. PARTICIPANTS: One thousand and eighty-three respondents aged 65 and older who consume alcohol. MAIN MEASURES: Participants' alcohol consumption was classified as Harmful, Hazardous, or Healthwise, in the context of their specific health status, using the Alcohol-Related Problems Survey classification algorithm. KEY RESULTS: Overall, 14.5 % of older drinkers (95 % CI: 12.1 %, 16.8 %) consumed alcohol above the NIAAA's recommended limits. However, when health status was taken into account, 37.4 % of older drinkers (95 % CI: 34.9 %, 40.0 %) had Harmful consumption and 53.3 % (95 % CI: 50.1 %, 56.6 %) had either Hazardous or Harmful consumption. Among light/moderate drinkers, the proportions were 17.7 % (95 % CI: 14.7 %, 20.7 %) and 28.0 % (95 % CI: 24.8 %, 31.1 %), respectively. Male drinkers had significantly greater odds of Hazardous/Harmful consumption than female drinkers (OR = 2.14 [95 % CI: 1.77, 2.6]). Black drinkers had worse health status and significantly greater odds of Hazardous/Harmful consumption than white drinkers (OR = 1.49; 95 % CI: 1.02, 2.17), despite having no greater prevalence of drinking in excess of NIAAA-recommended limits. CONCLUSION: Most older Americans who drink are light/moderate drinkers, yet substantial proportions of such drinkers drink in a manner that is either harmful or hazardous to their health. Older adults with risky alcohol consumption are unlikely to be identified by health care providers if clinicians rely solely on whether patient consumption exceeds the NIAAA-recommended limits.

Prevalencia de trastornos relacionados con el consumo del alcohol en población penitenciaria condenada por delitos contra la seguridad vial / Prevalence of alcohol consumption related disorders in a prison population convicted of crimes against road safety

Introducción. El consumo de alcohol es la causa de un elevado número de accidentes de tráfico, por lo que se han endurecido las leyes para evitarlo. A pesar de ello hay personas que las infringen e ingresan en prisión por conducir bajo los efectos del alcohol. Se investiga si estas personas son bebedores ocasionales o bien son enfermos alcohólicos. Material y Método. Estudio transversal de 50 internos penitenciarios por delitos contra la seguridad vial, entrevistados acerca de su consumo alcohólico, antecedentes psicopatológicos y delictivos. Resultados. El 88% presenta indicadores de alcoholismo y la mayoría consume otras drogas. Sólo en el 10% se ha detectado psicopatología previa. El 72% tiene antecedentes penitenciarios, la mitad por delitos con violencia. Socialmente están adaptados, 39 años de edad media, son españoles (86%), tienen familia y trabajo regular (76%). Conclusiones. La mayoría de internos por delitos contrala seguridad vial son alcohólicos, pero pocos son detectados. Su enfermedad genera otras conductas delictivas, siendo necesario su tratamiento para evitar la reincidencia y un proceso de exclusión social (AU)

Introduction. Alcohol consumption is a major cause of traffic accidents, so that stricter laws have been enacted to avoid it. Despite this, there are still persons who break the law and go to prison because of driving under the effects of alcohol. We have investigated if these persons are occasionally alcohol drinkers or if they are alcoholics with difficult to modify alcohol patterns. Material and methods. A cross-sectional study including 50 inmates from two prisons who had committed traffic crimes were interviewed about their alcohol consumption habits and their criminal and psychopathological backgrounds. Results. 88% had indicators of alcoholism and most consumed other drugs. Previous psychopathology signs were only detected in 10% of the sample. A total of 72% had previous criminal records, half because of violent offences. They were socially adapted, with mean age 39 years, Spanish (86%), had a stable job and family (76%). Conclusions. Most of the inmates due to traffic rimes are alcoholic, but very few are detected. Their alcohol consumption generates other criminal conduct, treatment being necessary in order to avoid relapse and social exclusion (AU)

Addiction research centres and the nurturing of creativity: the National Institute on Alcohol Abuse and Alcoholism.

The aim of this paper is to present a concise account of the history, mission, structure and some recent achievements of the US National Institute on Alcohol Abuse and Alcoholism (NIAAA). Created by the US Congress 40 years ago, the NIAAA has evolved from an entity charged mainly with building a national system of alcoholism treatment services to one with responsibility for developing, nurturing and supporting the biomedical and behavioral science foundation necessary to reduce the significant domestic and global public health impact of alcohol use disorders. The NIAAA is unique in that it functions both as a funding agency, supporting research at universities and other external, or 'extramural' research institutions, and is also a research institution itself, where alcohol research is carried out in-house, or 'intramurally'. Of a $450.2 million 2009 Congressional Appropriation, approximately 90% was devoted toward the former and approximately 10% towards the latter objective. The current NIAAA Strategic Plan builds on a new organizing principle for long-range research planning, based on a life-span perspective that recognizes that human biology and behavior continue to change throughout life and changes occurring throughout the life-span affect individuals' drinking patterns as well as the decisions they may make to change their drinking habits or to seek help for alcohol use problems. Within this framework, major efforts are currently being devoted to educating practitioners on clinically useful, science-based assessment and treatment methods that exist today, and development of personalized new treatments for tomorrow.

The recovery spectrum: from self-change to seeking treatment.

Recent innovations in alcohol-focused interventions are aimed at closing the gap between population need and the currently uncommon use of alcohol treatment services. Guided by population data showing the heterogeneity of alcohol problems and the occurrence of natural remissions from problem drinking without treatment, alcohol services have begun to expand beyond clinical treatment to offer the untreated majority of individuals with alcohol-related problems accessible, less-intensive services that use the tools of public health practice. These services often are opportunistic, meaning they can be provided in primary-care or other unspecialized health care or community settings. They also can be delivered by nonspecialists, or can be used by people themselves to address problems with alcohol without entering the health care system. This developing spectrum of services includes screening and brief interventions, guided self-change programs, and telehealth options that often are targeted and tailored for high-risk groups (e.g., college drinkers). Other efforts aimed at reducing barriers to care and increasing motivation to seek help have utilized individual, organizational, and public health strategies. Together, these efforts have potential for helping the treatment field reach people who have realized that they have a drinking problem but have not yet experienced the severe negative consequences that may eventually drive them to seek treatment. Although the evidence supporting several innovations in alcohol services is preliminary, some approaches are well established, and collectively they form an emerging continuum of care for alcohol problems aimed at increasing service availability and improving overall impact on population health.

Environmental approaches to prevention in college settings.

Because of concerns regarding drinking among college students and its harmful consequences, numerous prevention efforts have been targeted to this population. These include individual-level and community-level interventions, as well as other measures (e.g., online approaches). Community-level interventions whose effects have been evaluated in college populations include programs that were developed for the community at large as well as programs aimed specifically at college students, such as A Matter of Degree, the Southwest DUI Enforcement Project, Neighborhoods Engaging With Students, the Study to Prevent Alcohol-Related Consequences, and Safer California Universities. Evaluations of these programs have found evidence of their effectiveness in reducing college drinking and related consequences. The most effective approaches to reducing alcohol consumption among college students likely will blend individual-, group-, campus-, and community-level prevention components.

The Alcohol Policy Information System (APIS) and policy research At NIAAA.

Public policies have the potential to prevent the adverse consequences of alcohol consumption on a larger scale than any other category of interventions. However, measuring the effects of specific policies on alcohol-related behaviors and health outcomes is difficult and presents a variety of daunting challenges. One important challenge stems from the nonexperimental nature of most policy research, which makes it difficult to distinguish between causal relationships and noncausal associations. Another key challenge arises from the complexity of alcohol-related behaviors and outcomes and the wide range of potential effects that specific policy interventions may have on different groups and actors in various contexts. A third important challenge involves the difficulty in accurately characterizing the policies to be studied, which can be attributed largely to the arcane legal framework of statutes and regulations in which policies are created. This challenge is magnified by the enormous variety of alcohol-related public policies that have been adopted at all levels of government and the myriad variations in specific provisions that are embedded in the laws and regulations. Valid analysis of policy effects depends on surmounting all of these challenges and accurately characterizing policies and discerning the true causal effects of those policies on well-specified outcomes of interest.

NIAAA: advancing alcohol research for 40 years.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has been the lead Federal agency responsible for scientific research on alcohol and its effects for 40 years. During that time, NIAAA has conducted and funded groundbreaking research, distilled and disseminated those research findings to a broad audience, and ultimately improved public health. Among NIAAA's many significant contributions are the National Epidemiologic Survey on Alcohol and Related Conditions, the largest survey ever conducted on alcohol and associated psychiatric and medical conditions; investment in research to identify the genes underlying vulnerability to alcoholism; creation of the Collaborative Studies on Genetics of Alcoholism, a study of the genetics of alcoholism in a human population; leadership in exploring the effects of alcohol on fetal development and on a variety of diseases and organ systems; fostering alcoholism treatment, including supporting a medications development program that has funded more than 30 Phase 2 trials and 15 human laboratory studies; international collaborations and work across the National Institutes of Health; influential research on preventing alcohol problems through community programs as well as policy changes; and the translation of research findings to everyday practice, including the production of award-winning clinician training materials.

The past and future of research on treatment of alcohol dependence.

Research on the treatment of alcoholism has gained significant ground over the past 40 years. Studies such as the National Institute on Alcohol Abuse and Alcoholism's Project MATCH, which examined the prospect of tailoring treatments for particular people to better suit their needs, and Project COMBINE, which examined in-depth, cognitive-behavioral therapy and medical management, helped pave the way for a new way of approaching alcoholism treatment. New findings garnered through the National Epidemiologic Survey on Alcohol and Related Conditions further defined the problem. At the heart of this research has been the development of procedures to characterize, measure, and monitor the fidelity to a particular conceptual psychotherapeutic approach so that clear comparisons can be made between conceptually and technically distinct approaches. Advances in scientific methodology and statistics have provided tools to analyze complex datasets. The resulting findings mark an improvement over the first models of treatment developed decades ago, which tended to focus on anecdotal findings and assumptions. This hard-earned progress has enabled scientists today to move ahead and address the next set of challenges. Future research, coupled with a restructured treatment system capable of making new scientific findings rapidly available to the community, hold the key to significantly improving treatment outcomes and reducing suffering from alcohol-related disorders.

Fetal alcohol spectrum disorders: from research to policy.

Forty years ago, alcohol was not commonly recognized as a teratogen, an agent that can disrupt the development of a fetus. Today, we understand that prenatal alcohol exposure induces a variety of adverse effects on physical, neurological, and behavioral development. Research supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has contributed to the identification of the range and prevalence of fetal alcohol spectrum disorders (FASD), as well as methods for prevention and treatment of FASD. The worldwide prevalence and high personal and societal costs of FASD speak to the importance of this research. This article briefly examines some of the ways that NIAAA has contributed to our understanding of FASD, the challenges that we still face, and how this research is translated into changes in public policy.