Vulnerability For Alcohol Use Disorder Research Articles

Impaired Expression of Mu- and Kappa-Opioid Receptor mRNA in the Midbrain of Rats with Prenatal Alcohol Intoxication

Disruption of normal epigenetic reprogramming during the prenatal period under the influence of exogenous factors affects fetus development and adult phenotype formation. The mechanisms through which determinants, such as maternal alcohol intake, contribute to the formation of an alcohol-vulnerable phenotype later in life still remain unclear. In this paper, we suggest that alteration in the reinforcing properties of ethanol in prenatally alcohol-exposed subjects may be associated with transcriptional dysregulation of the brain opioid receptor genes. We compared voluntary alcohol intake and levels of mRNA coding for μ- (MOP) and κ-opioid (KOP) receptors in the mesolimbic areas of adult male offspring of the female Wistar rats having received 10% ethanol as the only source of liquid throughout pregnancy or water (control). We found that prenatally alcohol exposed rats had higher alcohol preference on PND60 (free-choice paradigm) and lower mRNA expression for both MOP and KOP in the midbrain compared to the control. This suggests a potential link between prenatal alcohol, dysfunction of the brain opiate system and adult vulnerability for alcohol use disorder.

Vulnerability for alcohol use disorder after adverse childhood experiences (AUDACE): protocol for a longitudinal fMRI study assessing neuropsychobiological risk factors for relapse

BackgroundAdverse childhood experiences (ACE) are common and may predispose affected individuals to various health problems, including alcohol use disorder (AUD). Although a relationship between ACE and AUD has been well-established,...

Sex/gender differences in brain function and structure in alcohol use: A narrative review of neuroimaging findings over the last 10 years.

Over the last 10years, rates of alcohol use disorder (AUD) have increased in women by 84% relative to a 35% increase in men. Rates of alcohol use and high-risk drinking have also increased in women by 16% and 58% relative to a 7% and 16% increase in men, respectively, over the last decade. This robust increase in drinking among women highlights the critical need to identify the underlying neural mechanisms that may contribute to problematic alcohol consumption across sex/gender (SG), especially given that many neuroimaging studies are underpowered to detect main or interactive effects of SG on imaging outcomes. This narrative review aims to explore the recent neuroimaging literature on SG differences in brain function and structure as it pertains to alcohol across positron emission tomography, magnetic resonance imaging, and functional magnetic resonance imaging modalities in humans. Additional work using magnetic resonance spectroscopy, diffusion tensor imaging, and event-related potentials to examine SG differences in AUD will be covered. Overall, current researchon the neuroimaging ofAUD, alcohol consumption, or risk of AUD is limited, and findings are mixed regarding the effect of SG on neurochemical, structural, and functional mechanisms associated with AUD. We address SG disparities in the neuroimaging of AUD and propose a call to action to include women in brain imaging research. Future studies are crucial to our understanding of the neurobiological underpinnings of AUD across neural systems and the vulnerability for AUD among women and men.

Increased alcohol preference and intake in nicotine-preferring rats

ABSTRACT Background Alcohol and tobacco are among the leading substances that are misused together and shared genetic vulnerability is likely. Increased susceptibility to nicotine self-administration has been shown in alcohol-preferring rat-lines. However, a nicotine-preferring (nP) rat-line has not been studied for alcohol preference. Objectives To evaluate alcohol preference and intake in male and female nP rats. We hypothesized that nP rats and females would drink more ethanol than control rats and males, respectively. Methods nP rats are being selectively outbred for high oral nicotine intake at Ege University. Seventeen nP (18th generation) and 20 naïve female and male SD rats, not previously exposed to alcohol or nicotine, were used. Twelve-week-old rats were given intermittent access to 20% ethanol in a 2-bottle-choice-procedure for six weeks. After one week withdrawal, six weeks of oral nicotine self-administration was applied. Results nP rats drank significantly more ethanol than controls and their preference for ethanol over water was higher. Female rats’ ethanol intake was higher than males’. The nP rats’ nicotine preference and intake were higher than controls, and they gained less weight. Conclusion We have shown for the first time that nP rats also have high alcohol intake. Our results support the hypothesis that shared genetic factors may underlie concurrent addiction to nicotine and alcohol and have translational value in understanding their misuse. Considering the increased vulnerability for alcohol use disorder in smokers and sex differences observed, early preventive measures in families with a history of tobacco addiction, specifically targeting female members, could have public health benefits.

Binge Drinking May Offer Clues About Risk for AUD

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessBinge Drinking May Offer Clues About Risk for AUDJoAnn BlakeJoAnn BlakeSearch for more papers by this authorPublished Online:14 Sep 2017https://doi.org/10.1176/appi.pn.2017.9b6AbstractYoung social drinkers at risk for an alcohol use disorder (AUD) had consumption patterns that were markedly different from low-risk drinkers during a free-access intravenous alcohol self-administration session.Binge drinking may be an early indicator of vulnerability to alcohol use disorder (AUD) and should be carefully assessed as part of a clinical evaluation, suggests a study published on August 4 in AJP in Advance. “Identifying early phenotypic differences between vulnerable individuals and healthy control subjects could help identify those at higher risk [for AUD],” wrote Joshua L. Gowin, Ph.D., a postdoctoral researcher at the National Institutes of Health in Bethesda, Md., and colleagues.Defined as a pattern of drinking that brings the blood alcohol level to 0.08 g/dL or above, binge drinking may indicate vulnerability to AUD, according to researchers. The study consisted of 159 young social drinkers who had taken part in an experimental laboratory session where they self-administered alcohol. To be included, participants must have consumed at least five drinks on at least one occasion previously. After the participant ate a standard meal, an intravenous catheter was inserted into a vein in the subject’s forearm. Alcohol self-administration was conducted using the computer-assisted alcohol infusion system software, which controlled the rate of infusion of 6 percent v/v (volume/volume) alcohol in saline for each person, using a physiologically based pharmacokinetic model for alcohol distribution and metabolism that accounts for sex, age, height, and weight. Researchers tested the hypothesis that risk factors for AUD—including family history of alcoholism, male sex, behavioral impulsivity, and low level of response to alcohol—would predict the rate of binging during an individual alcohol consumption session. Overall, 60 participants reached a binge-level exposure. A greater percentage of relatives with alcoholism (hazard ratio: 1.04), male sex (hazard ratio: 1.74), and higher impulsivity (hazard ratio: 1.17) were associated with a higher rate of binging throughout the session. Participants with all three of these risk factors had the highest rate of binging throughout the session compared with the lowest risk group (hazard ratio: 5.27). Level of response to alcohol was not a significant predictor of the rate of binging throughout the session.The study demonstrated that alcohol consumption patterns of young social drinkers at risk for AUD varied markedly from young low-risk drinkers. Researchers found that vulnerable drinkers showed higher rates of binging throughout the session and a greater overall exposure to alcohol. To the investigators’ knowledge, this is the first large pharmacokinetically controlled study to suggest that risk factors for AUD may lead to different patterns of drinking in young social drinkers who have not yet developed the disorder. The study was supported by the National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research. Development of the software used for the intravenous alcohol self-administration session was supported by Sean O’Connor, M.D., of the Indiana Alcohol Research Center. ■“Vulnerability for Alcohol Use Disorder and Rate of Alcohol Consumption” can be accessed here. ISSUES NewArchived

Vulnerability for Alcohol Use Disorder and Rate of Alcohol Consumption.

Although several risk factors have been identified for alcohol use disorder, many individuals with these factors do not go on to develop the disorder. Identifying early phenotypic differences between vulnerable individuals and healthy control subjects could help identify those at higher risk. Binge drinking, defined as reaching a blood alcohol level of 80 mg%, carries a risk of negative legal and health outcomes and may be an early marker of vulnerability. Using a carefully controlled experimental paradigm, the authors tested the hypothesis that risk factors for alcohol use disorder, including family history of alcoholism, male sex, impulsivity, and low level of response to alcohol, would predict rate of binging during an individual alcohol consumption session. This cross-sectional study included 159 young social drinkers who completed a laboratory session in which they self-administered alcohol intravenously. Cox proportional hazards models were used to determine whether risk factors for alcohol use disorder were associated with the rate of achieving a binge-level exposure. A greater percentage of relatives with alcoholism (hazard ratio: 1.04, 95% CI=1.02-1.07), male sex (hazard ratio: 1.74, 95% CI=1.03-2.93), and higher impulsivity (hazard ratio: 1.17, 95% CI=1.00 to 1.37) were associated with a higher rate of binging throughout the session. Participants with all three risk factors had the highest rate of binging throughout the session compared with the lowest risk group (hazard ratio: 5.27, 95% CI=1.81-15.30). Binge drinking may be an early indicator of vulnerability to alcohol use disorder and should be carefully assessed as part of a thorough clinical evaluation.

Can routine information from electronic patient records predict a future diagnosis of alcohol use disorder?

Objective: To explore whether information regarding potentially alcohol-related health incidents recorded in electronic patient records might aid in earlier identification of alcohol use disorders.Design: We extracted potentially alcohol-related information in electronic patient records and tested if alcohol-related diagnoses, prescriptions of codeine, tramadol, ethylmorphine, and benzodiazepines; elevated levels of gamma-glutamyl-transferase (GGT), and mean cell volume (MCV); and new sick leave certificates predicted specific alcohol use disorder.Setting: Nine general practitioner surgeries with varying size and stability.Subjects: Totally 20,764 patients with active electronic patient record until data gathering and with a history of at least four years without a specific alcohol use disorder after turning 18 years of age.Methods: The Cox proportional hazard analysis with time-dependent covariates of potential accumulated risks over the previous four years.Main outcome measures: Time from inclusion until the first specific alcohol use disorder, defined by either an alcohol specific diagnostic code or a text fragment documenting an alcohol problem.Results: In the unadjusted and adjusted Cox-regression with time-dependent covariates all variables were highly significant with adjusted hazard ratios ranging from 1.25 to 3.50. Addictive drugs, sick leaves, GGT, MCV and International Classification for Primary Care version 2 (ICPC-2), and International Classification of Diseases version 10 (ICD-10) diagnoses were analyzed. Elevated GGT and MCV, ICD-10-diagnoses, and gender demonstrated the highest hazard ratios.Conclusions: Many frequent health problems are potential predictors of an increased risk or vulnerability for alcohol use disorders. However, due to the modest hazard ratios, we were unable to establish a clinically useful tool.KEY POINTSAlcohol is potentially relevant for many health problems, but current strategies for identification and intervention in primary health care have not been successful.Many frequent clinical problems recorded in electronic patient records may indicate an increased risk for alcohol related health problems.The hazard ratios were modest and the resulting predictive model was unsatisfactory for diagnostic purposes. If we accepted a sensitivity as low as 0.50, the specificity slightly exceeded 0.75. With a low prevalent condition, it is obvious that the false positive problem will be vast.In addition to responding to elevated blood levels of liver enzymes, general practitioners should be aware of alcohol as a potentially relevant factor for patients with repeated events of many mental and psychosocial diagnoses and new sick leaves and repeated prescriptions of addictive drugs.

Early social isolation augments alcohol consumption in rats.

There is a considerable degree of individual vulnerability for alcohol use disorder (AUD) as only a subpopulation of individuals who regularly consume alcohol develop AUD. It is therefore very important to understand the factors and mechanisms that contribute towards the individual risk for AUD. In this respect, social influences, in particular during development, may be relevant for AUD as disruptions in early social experiences are associated with an increased risk for AUD. Social play, the most prominent form of social behaviour shown by young mammals, is rewarding and considered to be important for social, emotional and cognitive development. Recent studies suggest that early social isolation, effectively depriving animals from social play, increases the risk for addictive behaviour. The aim of this study was therefore to explore the long-term consequences of early social isolation on alcohol consumption and motivation for alcohol. To this end, rats were socially isolated from postnatal days 21-42, followed by 4 weeks of social housing, and voluntary alcohol consumption and operant responding for alcohol were determined in adulthood. We observed enhanced levels of alcohol consumption in adulthood in previously isolated rats, whereas operant responding for alcohol was not altered. The impact of early social isolation was independent of the individual variation in alcohol consumption. These data indicate that social isolation, during a developmental period when social play is highly abundant, enhances the propensity to consume alcohol in adulthood. This implies that early social experience may be a protective factor against excessive alcohol use.

Adolescent social isolation does not lead to persistent increases in anxiety- like behavior or ethanol intake in female long-evans rats.

Clinically, early life stress and anxiety disorders are associated with increased vulnerability for alcohol use disorders. In male rats, early life stress, imparted by adolescent social isolation, results in long-lasting increases in a number of behavioral risk factors for alcoholism, including greater anxiety-like behaviors and ethanol (EtOH) intake. Several recent studies have begun to use this model to gain insight into the relationships among anxiety measures, stress, EtOH intake, and neurobiological correlates driving these behaviors. As prior research has noted significant sex differences in the impact of adolescent stress on anxiety measures and EtOH drinking, the current study was conducted to determine if this same model produces an "addiction vulnerable" phenotype in female rodents. Female Long Evans rats were socially isolated (SI; 1/cage) or group housed (GH; 4/cage) for 6weeks during adolescence. After this housing manipulation, behavioral assessment was conducted using the elevated plus maze, response to novelty in an open field environment, and the light/dark box. After behavioral testing, home cage EtOH drinking was assessed across an 8-week period. No group differences were detected in any of the behavioral measures of unconditioned anxiety-like behavior. Greater EtOH intake and preference were observed in SI females but these differences did not persist. The SI/GH model, which results in robust and enduring increases in anxiety measures and EtOH self-administration in male Long Evans rats, did not result in similar behavioral changes in female rats. These data, and that of others, suggest that adolescent social isolation is not a useful model with which to study neurobiological substrates linking antecedent anxiety and addiction vulnerability in female rats. Given the compelling epidemiological evidence that the relationship between chronic adolescent stress and alcohol addiction is particularly strong in women, there is clearly an urgent need to identify a more effective model with which to study these clinically important relationships in female rodents.