Novelty seeking as a moderator of familial risk for alcohol dependence

BACKGROUND: Disinhibitory personality traits such as high novelty seeking (NS) are moderately heritable, and individuals with substance use disorders (SUDs) frequently exhibit such traits. However, recent studies have cast doubt on the supposition that such traits are true familial risk factors for SUD and particularly for alcohol dependence. Another possibility is that familial risk interacts with personality-associated risk, in which case the association between personality and familial risk might depend on sample composition, accounting for the lack of consensus among studies to date. We examined this possibility by analyzing the association between NS and alcohol dependence in individuals at intermediate and high levels of familial risk for alcohol dependence. METHODS: Data from the Collaborative Study on the Genetics of Alcoholism, a multisite family study, were examined. Subjects were 1,111 adult siblings of alcohol-dependent index cases. Parental diagnoses of alcohol dependence and personality scores of NS from the Tridimensional Personality Questionnaire were used to predict alcohol dependence. RESULTS: A significant interaction between NS and familial risk for alcoholism was seen, such that NS was a significantly stronger predictor of alcohol dependence in subjects with one or more parents with alcohol dependence than in subjects without alcohol-dependent parents. CONCLUSIONS: Novelty seeking and familial risk interact so that the risk associated with high NS is magnified in families with parental alcohol dependence and NS is a moderator of familial risk. Accordingly, high NS is strongly associated with alcohol dependence in subjects with a parent diagnosed with alcohol dependence, but low NS may protect against the risk associated with familial alcoholism. This interaction may account for conflicting findings from studies that have examined this question previously.     

Characterization of South African adolescents with alcohol use disorders but without psychiatric or polysubstance comorbidity

Background: Individuals who begin drinking during early adolescence and exhibit externalizing pathology and disinhibitory/dysregulatory tendencies are more vulnerable to developing alcohol use disorders (AUDs) in adulthood. Previous research has focused on in‐treatment populations with substantial comorbid psychopathology and polysubstance use. Here, we characterize a unique sample of treatment‐naïve adolescents without such comorbidity to help identify vulnerable youth who may benefit from early intervention. Methods: We compared externalizing propensity, disinhibitory characteristics, and school performance in adolescents with AUDs (but without comorbid psychopathology or other substance use; n = 70) to those of demographically matched controls (n = 70). Within the AUD group, we compared measures of substance use and the disinhibitory syndrome between boys and girls with differing severity of externalizing propensity. Results: Adolescents with AUDs demonstrated more externalizing propensity and disinhibitory personality traits (impulsivity, novelty seeking, and excitement seeking), poorer self‐monitoring and response inhibition, more bullying and sexual risk‐taking behavior, poorer first‐language performance, and greater use of alcohol, cannabis, and nicotine (p < 0.05). Within the AUD group, participants with higher externalizing propensity began drinking earlier, more frequently, and for a longer duration than those with lower externalizing symptoms (p < 0.05). Disinhibitory features (personality, cognition, and behavior) were, however, not stronger in those with higher externalizing propensity. Conclusions: We suggest that the constructs of externalizing propensity and disinhibitory syndrome are useful in characterizing treatment‐naïve adolescents with AUDs but without comorbid psychopathology or polysubstance use. These results support the importance of these constructs in understanding adolescent AUDs, even when the frank externalizing diagnoses of childhood (oppositional defiant disorder and conduct disorder) are excluded.     

Diffusion tensor measures of the corpus callosum in adolescents with adolescent onset alcohol use disorders

Background: In adults, myelination injury is associated with alcoholism. Maturation of the corpus callosum is prominent during adolescence. We hypothesized that subjects with adolescent‐onset alcohol use disorders (AUD; defined as Diagnostic and Statistical Manual of Mental Disorders‐IV alcohol dependence or abuse) would have myelination mircostructural differences compared to controls. Methods: Adolescent subjects (25 males, 7 females) with an AUD (16.9 ± 1.2 years), who were recruited from substance abuse treatment programs and had co‐morbid mental disorders, and 28 sociodemographically similar healthy controls (17 males, 11 females; 15.9 ± 1.1 years) underwent a 3.0 T MRI diffusion tensor imaging scan. Results: Measures of rostral body fractional anisotropy (FA) were higher in the AUD group than in the control group. Compared to controls, mean diffusivity (MD) was lower, while FA was higher, in the AUD group in the isthmus region. Anterior corpus callosum mircostructural development differed in adolescents with AUD, as age was positively (not negatively) associated with rostrum MD and age was negatively (not positively) associated with rostrum FA. There were sex by group interactions in that control females had higher posterior midbody FA when compared to female adolescents with AUD. Conclusions: Lower MD and higher FA values in the AUD group suggest pre‐morbid vulnerability for accelerated prefrontal and temporo‐parietal myelin maturation that may enhance the risk for adolescent AUD. Significant (and opposite to developmentally expected) correlations were seen between anterior corpus callosum MD and FA measures and age in the AUD group, suggesting neurotoxic effects of alcohol on adolescent corpus callosum microstructure. As seen in adults, female adolescents with AUD may be especially vulnerable to corpus callosum mircostructural injury. Further diffusion tensor imaging studies of corpus callosum maturation in children at familial risk for alcoholism, and in those with AUD, need to be done to elucidate these mechanisms.     

The alcohol use disorders identification test: an update of research findings

BACKGROUND: The Alcohol Use Disorders Identification Test (AUDIT) has been extensively researched to determine its capability to accurately and practically screen for alcohol problems. METHODS: During the 5 years since our previous review of the literature, a large number of additional studies have been published on the AUDIT, abbreviated versions of it, its psychometric properties, and the applicability of the AUDIT for a diverse array of populations. The current article summarizes new findings and integrates them with results of previous research. It also suggests some issues that we believe are particularly in need of further study. RESULTS: A growing body of research evidence supports the criterion validity of English version of the AUDIT as a screen for alcohol dependence as well as for less severe alcohol problems. Nevertheless, the cut-points for effective detection of hazardous drinking as well as identification of alcohol dependence or harmful use in women need to be lowered from the originally recommended value of 8 points. The AUDIT-C, the most popular short version of the AUDIT consisting solely of its 3 consumption items, is approximately equal in accuracy to the full AUDIT. Psychometric properties of the AUDIT, such as test-retest reliability and internal consistency, are quite favorable. Continued research is urged to establish the psychometric properties of non-English versions of the AUDIT, use of the AUDIT with adolescents and with older adults, and selective inclusion of alcohol biomarkers with the AUDIT in some instances. CONCLUSIONS: Research continues to support use of the AUDIT as a means of screening for the spectrum of alcohol use disorders in various settings and with diverse populations.     

Parallels to early onset alcohol use in the relationship of early onset smoking with drug use and DSM-IV drug and depressive disorders: findings from the National Longitudinal Epidemiologic Survey

This paper endeavored to determine (1) if early onset of regular tobacco use is as predictive of drug use and depressive disorders as it is of alcohol use disorders; and (2) if a biological commonality, as measured by a family history of alcoholism and both early onset and severity of disease, among all three disorders can be evidenced in a large nationally representative sample. Prevalences of lifetime drug use, drug abuse and dependence, and major depressive disorders, as well as indices of their severity, were compared among smoking groups defined by age at onset of regular tobacco use and among nonsmokers. Linear logistic regression analyses, controlling for important covariates, including a family history positive for alcoholism, were conducted to assess the relationship between age at smoking onset and drug use, abuse and dependence, as well as depressive disorders. Both objectives were met. Moreover, results suggest that smoking may play an equally, if not even more, insidious role than drinking in the use and development of dependence on illicit substances and depression.     

Health problems in adolescents with alcohol use disorders: self-report, liver injury, and physical examination findings and correlates

BACKGROUND: Although adolescent alcohol consumption has been found to be positively correlated with self-reported health problems, few studies have examined other health indicators. This study compared adolescents with alcohol use disorders (AUDs) and a community reference group on self-reported health problems, serum liver enzymes, and physical examination findings. The relevance of negative emotionality to understanding these health problems was also investigated. METHODS: The subjects were adolescents with AUDs recruited from clinical programs and classified as having DSM-IV alcohol dependence (n = 71) or alcohol abuse (n = 57) and reference adolescents without AUDs recruited from community sources (n = 131). The assessment of health status included self-reported health problems in 15 areas; serum liver enzyme assays, including gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase; and physical examination findings. Negative emotionality was determined by systematically combining scores from the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, the Child Behavior Checklist, and the Multidimensional Personality Questionnaire. RESULTS: Adolescent AUDs were associated with more self-reported health problems, higher gamma-glutamyl transpeptidase and alanine aminotransferase levels, and more physical examination abnormalities. Negative emotionality was highly correlated with self-reported health problems, mediated the relationship between AUDs and self-reported health problems, and was not correlated with serum liver enzyme levels or physical examination abnormalities. CONCLUSIONS: These results indicated that AUDs during adolescence were associated with health problems, including modest but demonstrable liver injury. Self-reported health problems were probably best understood, in this context, as a negative emotionality manifestation.     

Alcohol use disorders increase the risk for mechanical ventilation in medical patients

BACKGROUND: Annually, more than 300,000 patients receive mechanical ventilation in an intensive care unit in the United States. The hospital mortality for ventilated patients may approach 50%, depending on the primary diagnosis. In trauma and surgical patients, a diagnosis of alcohol use disorder (AUD) is common and is associated with a prolonged duration of mechanical ventilation. The objective of this study is to determine whether the presence of AUD and the development of alcohol withdrawal are associated with an increased use and duration of mechanical ventilation in patients with medical disorders that commonly require intensive care unit admission. METHODS: We performed a retrospective cohort study using the Nationwide Inpatient Sample, a large all-payer inpatient database representing approximately 1,000 hospitals. For the years 2002 to 2003, adult patients with 1 of the 6 most common diagnoses associated with medical intensive care unit admission were included in the study. Both univariate analysis and multivariable logistic regression were performed to determine whether AUD and alcohol withdrawal were independently associated with the use and duration of mechanical ventilation in these patients. RESULTS: There were a total 785,602 patients who fulfilled 1 of the 6 diagnoses, 26,577 (3.4%) had AUD, 3,967 (0.5%) had alcohol withdrawal, and 65,071 (8.3%) underwent mechanical ventilation (53% <96 hours, 47%> or =96 hours). Independent of the medical diagnosis, AUD was associated with an increased risk of requiring mechanical ventilation (13.7 vs 8.1%, odds ratio=1.49, 95% confidence interval [1.414; 1.574], p<0.0001) but was not associated with a prolonged duration of mechanical ventilation. However, the presence of alcohol withdrawal was associated with a longer duration of mechanical ventilation (57 vs 47%> or =96 hours, odds ratio=1.48, 95% confidence interval [1.266; 1.724], p<0.0001). CONCLUSIONS: In patients with medical diagnoses associated with intensive care unit admission, AUD increases the risk for mechanical ventilation while the development of alcohol withdrawal is associated with a longer duration of mechanical ventilation.     

Serotonin, impulsivity, and alcohol use disorders in the older adolescent: a psychobiological study

BACKGROUND: Alcohol use disorders (AUDs) among adolescents are associated with a high prevalence of conduct disorder (CD), much as type II alcoholism in adults is associated with impulsive-aggressive behavior and antisocial personality traits. Adults with impulsive personality disorders and AUD demonstrate diminished central serotonergic responsiveness to serotonergic agonists. Dysregulation of central serotonergic function may contribute to a vulnerability to impulsive-aggressive behavior, CD, and AUD. We studied older adolescents, both male and female, to examine the relationships between sex, dispositional impulsivity, aggressivity, CD, and responsiveness to serotonergic challenge with d,l fenfluramine (FEN) early in the development of AUD. METHODS: Thirty-six adolescents between the ages of 16 and 21 years were assessed for DSM-IV AUD and other Axis I disorders by using the Psychoactive Substance Use Disorders section of the Structured Clinical Interview for DSM III-R, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, and CD interviews. Impulsivity and aggressivity were assessed by the Barratt Impulsiveness Scale, Lifetime History of Aggression, Buss-Durkee Hostility Inventory, Eysenck Impulsiveness Questionnaire, Youth Self Report, and Multidimensional Personality Questionnaires. FEN was administered as 0.8 mg/kg to a maximum of 60 mg, and blood was sampled at fixed intervals for prolactin, cortisol, fenfluramine, and norfenfluramine levels. RESULTS: Eighteen adolescents (12 male, 6 female) with AUD scored significantly higher on all measures of impulsivity and aggressivity compared with 18 healthy controls (12 male, 6 female). There were no significant differences between groups in peak prolactin or cortisol responses (minus baseline), or area-under-the-curve determinations (AUC); however, 9 subjects with AUD and comorbid CD had significantly elevated cortisol AUC levels compared with subjects with AUD and no CD or with normal controls. In the total sample, cortisol AUC was associated positively with measures of aggression. CONCLUSIONS: Adolescents with early-onset AUD are characterized by impulsivity and aggressivity compared with healthy peers but do not demonstrate the diminished prolactin or cortisol responses to FEN characteristic of adult alcoholics with impulsive-aggression.     

Parenting mechanisms in links between parents' and adolescents' alcohol use behaviors

Background: Adolescence has been identified as a critical period with regard to the initiation and early escalation of alcohol use. Moreover, research on familial risk and protective processes provides independent support for multiple domains of parental influence on adolescent drinking; including parents’ own drinking behaviors, as well as the practices they employ to socialize their children. Despite this prevalence of findings, whether and how these distinct associations are related to one another is still not entirely clear. Methods: The present study used data from 4,731 adolescents and their parents to test the nature of associations between (a) parents’ frequencies of alcohol use and intoxication, and lifetime alcohol‐related problems, (b) adolescents’ perceptions of the parenting that they receive, and (c) adolescents’ prevalence of alcohol use and intoxication at 14 and 17½ years of age. As such, multiple mediation modeling was used to assess whether parental alcohol use behaviors influence adolescent alcohol use directly, or if they operate through indirect associations with various aspects of parenting that subsequently influence adolescent use. Results: Examination of simple associations demonstrated that maternal and paternal alcohol use behaviors were positively linked with adolescent use behaviors at 14 and 17½ years of age. Likewise, several parenting behaviors were independently associated with both parental and adolescent drinking. Examined collectively, multivariate path analyses indicated that associations between parents’ and adolescents’ alcohol‐related behaviors were mediated, in part, by adolescents’ perceptions of the parenting that they received, especially at 14 years of age. Furthermore, perceived parental monitoring and discipline had unique mediating capabilities, net the effects of all other parenting behaviors. Conclusions: This study demonstrates that parenting is an important mediator of the association between parental and adolescent drinking practices. An important area for future research will be to study how adolescents can avoid alcohol‐related problems despite being reared within a risk laden parenting environment and/or having parents who drink frequently.     

Drinks of the father: father's maximum number of drinks consumed predicts externalizing disorders,substance use,and substance use disorders in preadolescent and adolescent offspring

BACKGROUND: The maximum number of drinks consumed in 24 hr seems to be an interesting phenotype related to alcoholism. The goal of the present study was to determine in an epidemiologic sample whether this measure of drinking history in fathers predicted externalizing behavioral disorders, substance use, and substance abuse in preadolescent and adolescent offspring and whether any such associations would be independent of paternal alcohol dependence diagnoses. METHODS: Subjects were male and female twins from both age cohorts of the Minnesota Twin Family Study, a population-based longitudinal study, and were approximately 11 or 17 years of age, respectively, upon study enrollment. In both age cohorts, diagnoses of conduct disorder, oppositional defiant disorder, and attention-deficit/hyperactivity disorder served as outcome measures. In addition, measures of lifetime substance use and of the presence of symptoms of substance abuse were derived for the 11-year-old cohort when subjects were approximately 14 years old and diagnoses of substance abuse were derived for the older cohort at age 17. An extension of logistic regression using generalized estimating equations served to assess whether paternal maximum alcohol consumption predicted filial outcome measures. RESULTS: Paternal maximum alcohol consumption was consistently associated with conduct disorder, substance use, and substance abuse or dependence in male and female offspring. These associations were not mediated by a primary effect of paternal alcoholism. CONCLUSIONS: Paternal maximum alcohol consumption was uniquely associated with those offspring characteristics most reliably found in adolescent children of alcoholic parents. This phenotype might supplement DSM diagnoses of alcohol dependence to reduce the number of false positives in genetic research.     

Antisocial behavioral syndromes and DSM-IV alcohol use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions

BACKGROUND: Antisocial personality disorder (ASPD), syndromal adult antisocial behavior (AABS) without conduct disorder (CD) before age 15, and CD without progression to ASPD ("CD only") are highly prevalent among adults with alcohol use disorders (AUDs). Among patients in AUD treatment, antisocial behavioral syndromes are associated with more severe AUDs and poorer treatment outcomes. Comparative data concerning associations of antisocial syndromes with clinical characteristics of AUDs and the sociodemographic and clinical correlates of these syndromes among general population adults with AUDs have not previously been available. This study examines prevalences and correlates of antisocial syndromes among adults with lifetime Diagnostic and Statistical Manual--Version IV (DSM-IV) AUDs, and describes associations of these syndromes with clinical characteristics of AUDs, in the general U.S. population. METHODS: This report is based on the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (n=43,093, response rate=81%). Respondents (n=11,843) with lifetime AUDs were classified according to whether they met criteria for ASPD, AABS, "CD only," or no antisocial syndrome. Correlates of antisocial syndromes were examined using contingency table approaches and normal theory analyses of variance. Associations of antisocial syndromes with clinical characteristics of AUDs, including number of lifetime episodes, duration of longest or only episode, and alcohol consumption during period of heaviest drinking were examined using normal theory and logistic regression. RESULTS: Sociodemographic and clinical correlates of antisocial syndromes among respondents with AUDs were consistent with results from prior studies. Antisocial syndromes were significantly associated with phenomenology of AUDs, particularly ASPD with the most severe clinical presentations. Associations with AABS were similar to but more modest than those with ASPD; those with "CD only" were weaker and less consistent. Patterns of associations between antisocial syndromes and clinical characteristics of AUDs were generally similar between men and women. CONCLUSIONS: Antisocial syndromes, particularly ASPD, appear to identify a more pernicious clinical profile of AUDs among adults in the general U.S. population.     

Blood oxygen level dependent response and spatial working memory in adolescents with alcohol use disorders

BACKGROUND: Previous studies have suggested neural disruption and reorganization in young and older adults with alcohol use disorders (AUD). However, it remains unclear at what age and when in the progression of AUD changes in brain functioning might occur. METHODS: Alcohol use disordered (n = 15) and nonabusing (n = 19) boys and girls aged 15 to 17 were recruited from local high schools. Functional magnetic resonance imaging data were collected after a minimum of 5 days' abstinence as participants performed spatial working memory and simple motor tasks. RESULTS: Adolescents with AUD showed greater brain response to the spatial working memory task in bilateral parietal cortices and diminished response in other regions, including the left precentral gyrus and bilateral cerebellar areas (clusters > or =943 microl; p < 0.05), although groups did not differ on behavioral measures of task performance. No brain response differences were observed during a simple finger-tapping task. The degree of abnormality was greater for teens who reported experiencing more withdrawal or hangover symptoms and who consumed more alcohol. CONCLUSIONS: Adolescents with AUD show abnormalities in brain response to a spatial working memory task, despite adequate performance, suggesting that subtle neuronal reorganization may occur early in the course of AUD.     

Cigarette smoking and the risk for alcohol use disorders among adolescent drinkers

BACKGROUND: Cigarette smoking and alcohol use disorders (AUDs) are closely linked, but it is not clear whether higher rates of AUD among smokers are solely attributable to heavier drinking or, alternatively, whether smokers are more vulnerable to alcohol abuse and dependence than nonsmokers who drink comparable quantities. We sought to address this issue using data from a nationally representative U.S. sample of adolescents and young adults. Specifically, we analyzed the relationship between cigarette smoking, drinking, and AUDs. METHODS: Data were from the aggregated 2002 through 2004 U.S. National Survey on Drug Use and Health. Participants were randomly selected, household-dwelling adolescents and young adults (ages 12-20) from the noninstitutionalized, civilian population of the United States (N=74,836). Measurements included current DSM-IV alcohol abuse or dependence, number of drinks in the past 30 days, and past-year cigarette smoking, defined as having smoked more than 100 cigarettes across the lifetime and having smoked during the past year. RESULTS: Past-year smokers (prevalence=16.0%) drank in higher quantities than never-smokers, but were also at elevated risk for AUD when compared with never-smokers who drank equivalent quantities. The effect was observed across age groups, but was more prominent among younger adolescents. After adjusting for drinking quantity and sociodemographic variables, smokers had 4.5-fold higher odds of AUD than never-smokers [95% confidence interval (95% CI), 3.1-6.6]. Youths who reported smoking but did not cross the 100-cigarette threshold were at intermediate risk [odds ratio (OR), 2.3; 95% CI, 1.7-3.3]. Differences in AUD between smokers and never-smokers were most pronounced at lower levels of drinking. CONCLUSIONS: The results are consistent with a higher vulnerability to AUDs among smokers, compared with nonsmokers who drink equivalent quantities.     

Validity of the alcohol use disorders identification test in college students

BACKGROUND: High-risk alcohol use among college students is associated with accidents, partner violence, unwanted sexual encounters, tobacco use, and performance issues. The identification and treatment of high-risk drinking students is a priority for many college campuses and college health centers. The goal of this study was to test the psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT) in college students. METHODS: A convenience sample of students coming into a college health clinic was asked to complete the 10-question AUDIT and then participate in a research interview. The interview focused on assessing students for alcohol abuse and dependence by using the Composite International Diagnostic Interview Substance Abuse Module and timeline follow-back procedures to assess a 28-day drinking history. RESULTS: A total of 302 students met the eligibility criteria and agreed to participate in the study. The sample consisted of 185 females (61%) and 117 males (39%), with a mean age of 20.3 years. Forty students were abstinent, 88 were high-risk drinkers, and 103 met criteria for a 12-month history of dependence. Receiver operator curves demonstrated that the AUDIT had the highest area under the cure for detecting high-risk alcohol use (0.872) and the lowest for identifying persons with a lifetime history of alcohol abuse or dependence (0.775). An AUDIT cutoff score of 6 or greater demonstrated a sensitivity of 91.0% and a specificity of 60.0% in the detection of high-risk drinkers. CONCLUSIONS: The AUDIT has reasonable psychometric properties in sample of college students using student health services. This study supports the use of the AUDIT in this population.     

Adult transition from at-risk drinking to alcohol dependence: the relationship of family history and drinking motives

Background:  Prospective studies have not previously examined whether a family history of alcoholism and drinking motives conjointly predict a diagnosed DSM-IV alcohol abuse or dependence in adults, despite a large literature that each is associated with alcohol consumption. The focus of this study is the conjoint, prospective examination of these risk factors in a 10-year longitudinal study of adults who were at-risk drinkers at baseline.
Methods:  Prospective, population-based cohort of drinkers aged 18 or older from a Northeastern U.S. area initially evaluated for history of alcohol use disorders and drinking motives in 1991 to 1992. New onset dependence was studied in those who never met the criteria for alcohol dependence at baseline ( n  = 423), and new onset abuse was studied in those who never met the criteria for alcohol abuse at baseline ( n  = 301) and who did not develop dependence during the follow-up.
Results:  Family history significantly interacted with 2 baseline drinking motives in predicting new onsets of DSM-IV alcohol dependence: drinking to reduce negative affect (OR 3.38; 95% CI 1.05, 10.9) and drinking for social facilitation (OR 3.88; CI 1.21, 12.5). Effects were stronger after conditioning the drinking motives on having a positive family history of alcoholism. In contrast, in predicting new onsets of alcohol abuse, drinking motives did not have direct effects or interact with family history.
Conclusions:  Those who drank to reduce negative affect or for social facilitation at baseline were at greater risk of alcohol dependence 10 years later if they also had a family history of alcoholism. These results suggest an at-risk group that can be identified prior to the development of alcohol dependence. Further, the findings suggest utility in investigating the interaction of drinking motives with measured genetic polymorphisms in predicting alcohol dependence.