Family History Of Alcohol Use Disorder Research Articles

The Subjective Response to Nitrous Oxide is a Potential Pharmaco-Endophenotype for Alcohol Use Disorder: A Preliminary Study with Heavy Drinkers.

Background:Healthy people with a family history of alcohol problems show a pattern of subjective responses to alcohol that resemble those of affected probands. Studies on ketamine suggest that up-regulation of N-methyl-D-aspartate receptors (NMDARs) underlies these effects, and point to a pharmacologically-responsive endophenotype reflecting enhanced risk for alcohol-use disorders.Methods:Subjective stimulant and sedative effects were assessed before and during nitrous oxide (N2O; 50%) inhalation in heavy drinkers who were otherwise healthy.Results:Participants with an ostensible family history of alcohol-use disorders (n = 23) were distinguishable from those without such familial risk (n = 37) by an enhanced stimulation-to-sedation ratio during N2O inhalation.Conclusion:The pattern of subjective effects of N2O according to familial risk is remarkably similar to that previously seen with ketamine, supporting the idea of a common, NMDAR-mediated mechanism of action. N2O may prove to be a safe and accessible alternative to ketamine for probing heritable NMDAR dysregulation in neuropsychiatric disorders.

Autism and attention-deficit/hyperactivity disorder among individuals with a family history of alcohol use disorders.

Recent studies suggest de novo mutations may involve the pathogenesis of autism and attention-deficit/hyperactivity disorder (ADHD). Based on the evidence that excessive alcohol consumption may be associated with an increased rate of de novo mutations in germ cells (sperms or eggs), we examine here whether the risks of autism and ADHD are increased among individuals with a family history of alcohol use disorders (AUDs). The standardized incidence ratios (SIRs) of autism and ADHD among individuals with a biological parental history of AUDs were 1.39 (95% CI 1.34-1.44) and 2.19 (95% CI 2.15-2.23), respectively, compared to individuals without an affected parent. Among offspring whose parents were diagnosed with AUDs before their birth, the corresponding risks were 1.46 (95% CI 1.36-1.58) and 2.70 (95% CI 2.59-2.81), respectively. Our study calls for extra surveillance for children with a family history of AUDs, and further studies examining the underlying mechanisms are needed.

Acute Alcohol Response Phenotype in Heavy Social Drinkers is Robust and Reproducible

In 3 previously published works (Brumback etal., 2007, Drug Alcohol Depend 91:10-17; King etal., 2011a, Arch Gen Psychiatry 68:389-399; Roche and King, 2010, Psychopharmacology (Berl) 212:33-44), our group characterized acute alcohol responses in a large group of young, heavy binge drinkers (n=104) across a variety of subjective, eye-tracking, and psychometric performance measures. The primary goal of the current study was to directly replicate prior findings of alcohol response in heavy social drinkers (HD) in a second independent cohort (n=104) using identical methodology. A secondary goal was to examine the effects of family history (FH) of alcohol use disorders (AUD) on acute alcohol response in both samples. Participants attended 2 randomized laboratory sessions in which they consumed 0.8g/kg alcohol or a taste-masked placebo. At pre- and post-drink time points, participants completed subjective scales, psychomotor performance and eye-movement tasks, and provided salivary samples for cortisol determination. Results showed that the second cohort of heavy drinkers exhibited a nearly identical pattern of alcohol responses to the original cohort, including sensitivity to alcohol's stimulating and hedonically rewarding effects during the rising breath alcohol content (BrAC) limb, increases in sedation during the declining BrAC limb, a lack of cortisol response, and psychomotor and eye-tracking impairment that was most evident at peak BrAC. The magnitude and temporal pattern of these acute effects of alcohol in the second cohort were similar to the first cohort across all measures, with the exception of 3 eye-movement measures: pro- and antisaccade accuracy and antisaccade velocity. FH of AUD did not affect alcohol response in the first cohort, and this was replicated in the second cohort. In sum, in 2 independent samples, we have demonstrated that HD display a consistent and reliable sensitivity to alcohol's subjective effects and impairment of eye-tracking and psychomotor performance, which is not affected by FH status. This acute alcohol response phenotype in heavy, frequent binge drinkers appears to be robust and reproducible.

Atypical Spatial Working Memory and Task‐General Brain Activity in Adolescents with a Family History of Alcoholism

Altered behavioral performance and brain activation during spatial working memory (SWM) tasks have been demonstrated in individuals with an alcohol use disorder (AUD). It is possible that alterations in processing during SWM may be present prior to initiation of heavy alcohol use in adolescents with a family history of AUDs (family history positive [FHP]) and therefore represent a premorbid neural phenotype that could increase risk for developing an AUD. The goal of our study was to investigate group differences in brain activation during a SWM task between FHP adolescents and adolescents with no family history of AUDs (family history negative [FHN]), as well as examine the relationship between brain activation and individual differences in family history density (FHD) of AUDs. Eighteen FHP and 16 gender and age-matched FHN participants completed a SWM and vigilance task while undergoing a functional magnetic resonance imaging (fMRI) scan. There were no group differences in task performance. The FHN group demonstrated expected greater activation during the SWM than vigilance condition in the right middle frontal gyrus and dorsolateral prefrontal cortex, whereas the FHP group demonstrated comparable brain activation for both the more demanding and simple task conditions. Additionally, FHD was associated with greater activation of the right superior parietal cortex and less activation of the right cerebellum during the SWM task, but not during the vigilance task. Results suggest FHP adolescents demonstrate alterations in activation of prefrontal regions that are related more generally to the maintenance of top-down cognitive control and alterations in parietal and cerebellar regions that are specific to SWM. Alterations in top-down cognitive control may be a general risk factor for FHP adolescents, whereas SWM-specific alterations are seen as a function of family history loading.

Environmental influences predominate in remission from alcohol use disorder in young adult twins

Familial influences on remission from alcohol use disorder (AUD) have been studied using family history of AUD rather than family history of remission. The current study used a remission phenotype in a twin sample to examine the relative contributions of genetic and environmental influences to remission. The sample comprised 6183 twins with an average age of 30 years from the Australian Twin Registry. Lifetime history of alcohol abuse and dependence symptoms and symptom recency were assessed with a structured telephone interview. AUD was defined broadly and narrowly as history of two or more or three or more abuse or dependence symptoms. Remission was defined as absence of symptoms at time of interview among individuals with lifetime AUD. Standard bivariate genetic analyses were conducted to derive estimates of genetic and environmental influences on AUD and remission. Environmental influences alone accounted for remission in males and for 89% of influences on remission in females, with 11% due to genetic influences shared with AUD, which decreased the likelihood of remission. For women, more than 80% of influences on remission were distinct from influences on AUD, and environmental influences were from individual experiences only. For men, just over 50% of influences on remission were distinct from those on AUD, and the influence of environments shared with the co-twin were substantial. The results for the broad and narrow phenotypes were similar. The current study establishes young adult remission as a phenotype distinct from AUD and highlights the importance of environmental influences on remission.

Adolescent substance abuse: the effects of alcohol and marijuana on neuropsychological performance.

Adolescence is a period in which cognition and brain undergo dramatic parallel development. Whereas chronic use of alcohol and marijuana is known to cause cognitive impairments in adults, far less is known about the effect of these substances of abuse on adolescent cognition, including possible interactions with developmental processes. Neuropsychological performance, alcohol use, and marijuana use were assessed in 48 adolescents (ages 12 to 18), recruited in 3 groups: a healthy control group (HC, n = 15), a group diagnosed with substance abuse or dependence (SUD, n = 19), and a group with a family history positive for alcohol use disorder (AUD) but no personal substance use disorder (FHP, n = 14). Age, drinks per drinking day (DPDD), percentage days drinking, and percentage days using marijuana were considered as covariates in a MANCOVA in which 6 neuropsychological composites (Verbal Reasoning, Visuospatial Ability, Executive Function, Memory, Attention, and Processing Speed) served as dependent variables. More DPDD predicted poorer performance on Attention and Executive Function composites, and more frequent use of marijuana was associated with poorer Memory performance. In separate analyses, adolescents in the SUD group had lower scores on Attention, Memory, and Processing Speed composites, and FHP adolescents had poorer Visuospatial Ability. In combination, these analyses suggest that heavy alcohol use in adolescence leads to reduction in attention and executive functioning and that marijuana use exerts an independent deleterious effect on memory. At the same time, premorbid deficits associated with family history of AUD appeared to be specific to visuospatial ability.

Onset and course of alcoholism over 25 years in middle class men

Background: Patterns of drinking and alcohol problems change with age. However, few studies use multiple data points and detailed history spanning early adulthood to middle age. This study reports such data from 373 men in the San Diego Prospective Study. Methods: Data were generated at baseline (T1) at ∼age 20, and through face-to-face followup interviews ∼every 5 years in >90% of these eligible Caucasian and relatively higher educated men. Subjects were placed into 4 groups regarding their course: 62.5% with no alcohol use disorder (AUD); 17.2% with AUD onset <age 30 and a chronic course; 6.7% with onset ≥age 30 and no recovery; and 13.7% with AUD onset <age 30 and maintained remission for >5 years before the 25-year followup. Results: On a univariate level, low level of response (LR) to alcohol, family history of AUDs, and higher Novelty Seeking at ∼age 20 predicted AUDs with onset before age 30 (mean age ∼ 25), but among these only LR predicted later onset (mean age 38) as well. Additional predictors of AUDs included demography (lower education), and greater involvement with alcohol, drugs, and nicotine prior to T1. Sustained remission from AUDs among alcoholics was predicted by lower T1 and T10 drinking frequencies, and being separated or divorced at T10, along with a trend for higher Reward Dependence. Conclusion: These data indicate that information available in ages of the late teens to early twenties can help predict the future onset and course of AUDs, and underscore the importance of longitudinal studies in substance use disorders.

Family History of Alcohol-Use Disorders and Spatial Working Memory: Effects on Adolescent Alcohol Expectancies

Family history (FH) of alcohol-use disorders (AUDs) has been associated with frontal lobe deficits, more positive expectations for alcohol effects, and increased risk of developing AUDs. We tested the hypothesis that anterior brain regions mediate the relationship between FH of AUDs and alcohol expectancies in adolescents. Nondrinking adolescents (N = 50) ages 12-14 completed measures of FH of AUDs, alcohol expectancies, and substance use and performed spatial working memory and vigilance tasks during functional magnetic resonance imaging. Activation of the anterior cingulate significantly predicted alcohol expectancies (R(2)Delta = 9%, beta = .32, F(change) = 6.09, 1/43 df, p < .05). However, FH of AUDs was not associated with brain response or alcohol expectancies. Although a mediational model was not supported, activation in the anterior cingulate was linked to alcohol expectancies, such that adolescents with less neural differentiation to task demands had more positive expectancies for alcohol's effects. These results provide a greater understanding of the interrelations among risk factors for AUD and point to individuals who might be targeted for early, cognitively based interventions.

The relationship of behavioural undercontrol to alcoholism in higher-functioning adults

Externalising behaviours, including the personality characteristics of behavioural undercontrol (BU), represent one of several genetically influenced domains that impact on the alcoholism risk. Because genes explain only about 60% of the vulnerability toward alcohol use disorders (AUDs), an optimal understanding of how such behaviours affect the risk requires evaluation of their impact in the context of additional influences. Few studies have addressed this question regarding BU among relatively well-functioning adults. This paper presents results from testing a BU-based mediational model of risk in men from the San Diego Prospective Study. Structured research instruments were used with 430 adult Caucasian males to evaluate the performance of BU in predicting AUDs at the 15-year follow-up using Pearson product - moment correlations among domains and an AMOS-based structural equation model (SEM). While both the family history of AUDs (FHalc) and BU predicted alcohol-related outcome, BU by itself did not mediate the relationship of the FH to alcohol disorders. The impact of BU on alcohol problems was mediated by alcohol expectancies, peer drinking and by coping. The SEM explained 42% of the variance for AUDs. The current results indicate that BU contributed to the risk for alcohol-related problems, even among more highly functional subjects and after excluding the impact of the antisocial personality disorder, but by itself did not mediate the relationship of FH to outcome in these subjects.