Research on alcohol and adolescent brain development: opportunities and future directions

In the past 15 years, both human and animal studies have advanced our understanding of the effects of adolescent alcohol exposure on behavioral and neural development, particularly in the areas of the ontogeny of initial sensitivity and tolerance to alcohol, the consequences of adolescent alcohol exposure on subsequent drinking patterns, as well as cognitive and neural function. Despite these advances, there are still substantial gaps in our understanding of whether heavy adolescent drinking interferes with normal brain development at the cellular and molecular level, and if so, how these changes may translate into patterns of brain connectivity that result in the emergence of alcohol use disorders. This article discusses our current knowledge of the cellular and molecular brain changes that stem from heavy alcohol exposure, including binge patterns, during adolescence. Progress has been made in linking the behavioral effects of adolescent drinking to underlying cellular and molecular mechanisms. However, it is suggested that future research on the etiology and consequences of adolescent drinking use an integrative approach to this problem by combining multiple levels, including genetic, cellular and molecular, systems (neuroimaging), and behavioral, with an emphasis on integrating the different levels of analysis.     

A Prospective Study of Intraindividual and Peer Influences on Adolescents' Heterosexual Romantic and Sexual Behavior

Theories and empirical studies of adolescent sexual behavior have identified the contributions of personal attributes and social experiences; however, it is rare that models have clarified developmental pathways to adolescent sexual behavior that include (1) factors assessed prior to and early in adolescence and (2) dyadic experiences in adolescence that provide the opportunity for sexual behavior (i.e., dating). Using data from a prospective study, structural equation modeling was used to test a model predicting adolescent sexual behavior at age 19, denoted by the number of lifetime sexual partners. Predictors examined were sociability and impulsivity assessed at 30 months of age, physical characteristics and experiences with peers measured at age 12-13, the age of first romantic relationship, and frequency of alcohol use at age 16. The pathway to greater sexual involvement was marked by some desired personal attributes (e.g., sociability) and peer experiences (e.g., higher quality friendships). These associations were mediated, however, by earlier initiation of romantic relationships and more frequent use of alcohol in middle adolescence. Earlier initiation of romantic relationships and more frequent alcohol use were predicted by greater sociability and less impulsivity in childhood, higher quality friendships and greater peer acceptance in early adolescence, and a more mature appearance and physical attractiveness (among females) at age 13. The findings imply a complex pathway that leads to a greater accumulation of sexual partners by age 19. This pathway begins in childhood and includes individual qualities, peer acceptance, romantic relationships, and alcohol use.     

Chronic alcohol consumption from adolescence to adulthood in mice – Hypothalamic gene expression changes in insulin-signaling pathway

Adolescence is a developmental stage vulnerable to alcohol drinking-related problems, and alcohol exposure during adolescence may lead to long-lasting consequences. The hypothalamus is a key brain region for food and water intake regulation as well as weight control, and is one of the alcohol-sensitive brain regions. However, it is not known what the alcohol effect is on the hypothalamus following adolescent alcohol intake, chronically over adolescent development, at moderate levels. We employed a model of chronic moderate alcohol intake from adolescence to adulthood in mice, and analyzed the effect of alcohol on growth and weight gain, as well as hypothalamic gene expression patterns. The results indicated that chronic alcohol consumption during adolescence, even at moderate levels, led to both a reduction in weight gain in mice, and considerable gene expression changes in the hypothalamus. Pathway analysis and real-time PCR identified the type II diabetes mellitus and the insulin-signaling pathways as being the hypothalamic pathways affected by chronic alcohol. Our findings from the mouse alcohol consumption study therefore serve as a potential warning against alcohol consumption during adolescence, such as in teens and college students.     

Chronic intermittent toluene inhalation initiated during adolescence in rats does not alter voluntary consumption of ethanol in adulthood

Voluntary inhalation of organic solvents, such as toluene, is particularly prevalent in adolescent populations and is considered to be a contributing factor to substance use and dependence later in life. While inhalants are often the initial “drug” experienced during this period, alcohol is another substance readily abused by adolescent populations. Although both substances are thought to have similar actions within the brain, our understanding of the implications of adolescent inhalant abuse upon subsequent exposure to alcohol remains to be investigated. Thus, this study aimed to assess locomotor responses to acute ethanol and voluntary ethanol consumption following a period of toluene inhalation throughout adolescence/early adulthood. Adolescent male Wistar rats (postnatal day [PN] 27) inhaled air or toluene (3000 ppm) for 1 h/day, 3 days/week for 4 (PN 27–52) or 8 weeks (PN 27–80) to mimic the patterns observed in human inhalant abusers. Following the exposure period, cross-sensitization to acute ethanol challenge (0.5 g/kg, intra-peritoneally [i.p.]), and voluntary consumption of 20% ethanol in a chronic intermittent 2-bottle choice paradigm, were assessed. Hepatic ethanol and acetaldehyde metabolism and liver histopathology were also investigated. Chronic intermittent toluene (CIT) exposure throughout adolescence for up to 8 weeks did not alter the behavioral response to acute ethanol or voluntary consumption of ethanol in adulthood, although an age-dependent effect on ethanol consumption was observed (p < 0.05). Both liver function and pathology did not differ between treatment groups. Thus, in the paradigm employed, CIT exposure throughout adolescence and early adulthood did not predispose rats to subsequent locomotor sensitivity or voluntary consumption of ethanol in adulthood.     

Functional magnetic resonance imaging in studies of neurocognitive effects of alcohol use on adolescents and young adults

Alcohol use disorders (defined as alcohol abuse or dependence) are prevalent and serious problems among adolescents and young adults. Adolescence is a time of trying new experiences and activities that emphasize socializing with peers, and conforming to peer-group standards. These new activities may place young people at particular risk for initiating and continuing alcohol consumption. Exposing the brain to alcohol during adolescence may interrupt key processes of brain development, leading to cognitive impairment as well as to further escalation of alcohol use. Alcohol-induced adolescent learning impairments could affect academic and occupational achievements. Functional magnetic resonance imaging (fMRI) is a relatively new imaging technique that allows studying neurocognitive function. fMRI aims to determine the neurobiological correlate of behavior by identifying the brain regions that become active during the performance of specific tasks in vivo. The technique is non-invasive and relatively safe. This allows repeated studies to be carried out within a given subject. Several fMRI studies have been performed to evaluate neurocognitive function in adolescents and young adults with alcohol use disorders. Adolescents and young adults with alcohol use disorders had abnormalities in brain response to a working memory task. The results of the studies of cue reactivity and craving responses in young people suggest that the elevated physiological response and altered cognitive reactions to alcohol are involved in the pathogenesis of alcohol dependence in adolescents and young adults. Future fMRI studies may help ascertain the adverse affects of alcohol on brain function during early neurodevelopmental stages. fMRI may be uniquely powerful in the delineation of the underlying pathophysiology of alcohol use disorders in adolescents and young adults.     

Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry

Alcohol use increases across adolescence and is a concern in the United States. In humans, males and females consume different amounts of alcohol depending on the age of initiation, and the long-term consequences of early ethanol consumption are not readily understood. The purpose of our work was to better understand the immediate and long-term impact of ethanol exposure during adolescence and the effects it can have on behavior and dopaminergic responsivity. We have assessed sex differences in voluntary ethanol consumption during adolescence and adulthood and the influence of binge ethanol exposure during adolescence. We have observed that males are sensitive to passive social influences that mediate voluntary ethanol consumption, and early ethanol exposure induces long-term changes in responsivity to ethanol in adulthood. Exposure to moderate doses of ethanol during adolescence produced alterations in dopamine in the nucleus accumbens septi during adolescence and later in adulthood. Taken together, all of these data indicate that the adolescent brain is sensitive to the impact of early ethanol exposure during this critical developmental period.     

Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence

Studies over the last decade demonstrate that adolescence is a brain maturation period from childhood to adulthood. Plastic and dynamic processes drive adolescent brain development, creating flexibility that allows the brain to refine itself, specialize, and sharpen its functions for specific demands. Maturing connections enable increased communication among brain regions, allowing greater integration and complexity. Compelling evidence has shown that the developing brain is vulnerable to the damaging effects of ethanol. It is possible to infer, therefore, that alcohol exposure during the critical adolescent developmental stages could disrupt the brain plasticity and maturation processes, resulting in behavioral and cognitive deficits. Recent neuroimaging studies have provided evidence of the impact of human adolescent drinking in brain structure and functions. Findings in experimental animals have also given new insight into the potential mechanisms of the toxic effects of ethanol on both adolescent brain maturation and the short- and long-term cognitive consequences of adolescent drinking.Adolescence is also characterized by the rapid maturation of brain systems mediating reward and by changes in the secretion of stress-related hormones, events that might participate in the increasing in anxiety and the initiation pattern of alcohol and drug consumption. Studies in human adolescents demonstrate that drinking at early ages can enhance the likelihood of developing alcohol-related problems. Experimental evidence suggests that early exposure to alcohol sensitizes the neurocircuitry of addiction and affects chromatin remodeling, events that could induce abnormal plasticity in reward-related learning processes that contribute to adolescents' vulnerability to drug addiction.In this article, we review the potential mechanisms by which ethanol impacts brain development and lead to brain impairments and cognitive and behavioral dysfunctions as well as the neurobiological and neurochemical processes underlying the adolescent-specific vulnerability to drug addiction.     

Alcohol Use Among Adolescent Mothers: Heterogeneity in Growth Curves,Predictors, and Outcomes of Alcohol Use Over Time

This paper examines patterns of alcohol use over a 10-year period in a sample of adolescent mothers and includes both predictors and outcomes of young mothers' alcohol use patterns over time. This study used mixture modeling to identify latent trajectory classes based on alcohol consumption over 10 years. Results indicate that there is significant heterogeneity in alcohol use trajectories of adolescent mothers during the transition from adolescence to adulthood as well as significant predictors and outcomes that vary by latent class trajectory. Specifically, measures of the consumption of alcohol by both quantity and frequency yielded multiple latent trajectory classes. Alcohol quantity measures yielded a two-class model with higher and lower quantity users. Age at first drink significantly differentiated between the two classes indicating that the younger the respondent was, the more likely she belonged to the higher quantity user class. In addition, members of the higher quantity class had significantly more negative outcomes in adulthood. The second measure of alcohol consumption, alcohol frequency, yielded a four-class solution consisting of low-level users, early decliners, late decliners, and increasers. As with alcohol quantity, age at first drink significantly differentiated between classes, as did age at first birth, in the expected direction. Similarly, two classes with the greatest growth and patterns of use over time, late decliners and increasers, had significantly worse outcomes in adulthood. The results suggest that identifying underlying heterogeneity in alcohol use can be informative with regard to both predictors and outcomes for young women who were adolescent mothers. Results suggest that there are possible higher order factors that can account for the results of this study.     

Childhood maltreatment and the risk of substance problems in later life

This paper examines the risk of developing problems in adolescence and adulthood, particularly those associated with substance use, as a consequence of experiencing physical or sexual abuse during childhood. We review both retrospective and prospective research, conducted with both adolescent and adult respondents. Although there are some marked discrepancies in the findings from retrospective and prospective studies, these are probably due to differences in methodology, particularly between using official records and self-report to identify cases of abuse. Despite the wide range of methodologies and samples used in these studies, most indicate that the experience of childhood abuse is a risk factor for a number of common mental disorders in adolescence and adulthood, including alcohol and drug-related problems. In many cases, the experience of abuse appears to lead in later life to increased feelings of depression and anxiety which, while not sufficient to result in the diagnosis of a mental health disorder, place the victims at greater risk of developing substance problems. Multivariate studies indicate that this positive association remains even when controlling for important variables such as the presence of parental alcohol problems. The paper concludes with a number of recommendations for future research, so that it can be established whether the risk arises specifically from child abuse or neglect, or from the more general impact on child development of adverse family relationships.     

Concurrent alcohol and tobacco use during early adolescence characterizes a group at risk

AIMS: To investigate whether concurrent alcohol and tobacco use during early adolescence characterizes a subgroup that differs from users of one substance only regarding several risk factors for later substance use problems. METHODS: Participants were from a prospective longitudinal cohort study of 384 children at risk for later psychopathology, with the majority being born with obstetric complications and psychosocial adversities. Assessments of adolescent drug consumption and related intrapersonal characteristics were obtained at age 15. RESULTS: Compared to consumers of alcohol only, 15-year-olds drinking and smoking during the same time period (past 4 weeks) had significantly higher levels of consumption and more excessive use of alcohol, started drinking at an earlier age, had higher scores on the Fagerstr?m Test for Nicotine Dependence, and more cannabis use. This group could be distinguished from users of alcohol only by higher novelty seeking and more positive alcohol effect expectancies. Compared to consumers of tobacco only, concurrent users reported higher nicotine dependence and more cannabis use. No significant differences were observed regarding frequency and age at initiation of tobacco use, tobacco-related sensitivity, self-efficacy and instrumentality as well as novelty seeking. CONCLUSIONS: Concurrent alcohol and tobacco use during early adolescence is associated with characteristics that are well known as risk factors for later alcohol use problems and dependence and that should be targeted by prevention programs.     

Social competence among urban minority youth entering middle school: relationships with alcohol use and antisocial behaviors

Social competence is increasingly multidimensional during adolescence as young people encounter a variety of new social situations and can respond with a broad range of appropriate behaviors. However, research on social competence has focused more on children than adolescents. The present study examined the relationships between components of social competence (e.g., assertiveness and social confidence) and adolescent problem behaviors including alcohol use and antisocial behaviors (e.g., aggression and delinquency). A survey was administered to 6th grade students (N=2411) entering 20 New York City public and parochial middle schools and again a year later in the 7th grade. Findings indicated that verbal aggression was reported most frequently among students (93%), followed by physical aggression (69%), delinquent behaviors (53%), and alcohol use (16%). Structural equation modeling indicated that while assertiveness was protective in terms of adolescent problem behaviors, social confidence--the level of confidence that students had in initiating social interactions including dating--was associated with greater alcohol use and antisocial behavior both cross-sectionally and longitudinally. Additional analyses revealed that social confidence related to the initiation of dating (e.g., asking someone out for a date or having a conversation with a member of the opposite sex) was most strongly correlated with each problem behavior outcome. These findings suggest that social confidence, particularly as it relates to precocious dating behavior during early adolescence, is a risk factor for the early initiation of alcohol use and antisocial behavior.     

Prevalence and factors associated with behavioral disorders in adolescents: a population-based study

This study proposed to estimate the prevalence of behavioral disorders and associated factors in adolescents (11-15 years), using a cross-sectional design (n = 1,145). Subjects answered a self-administered questionnaire. Behavioral disorder was assessed with the Mini International Neuropsychiatric Interview (MINI). The study analyzed disorders in relation to gender, age, socioeconomic status, schooling, failure in school, religion, smoking, sedentary lifestyle, alcohol consumption, drug use, depression, and bullying (as victim). Ordinal regression was used for the statistical analysis, with a hierarchical model for the outcome. An estimated 29.2% of the sample presented behavioral disorders. In the multivariate analysis, the odds ratio for a male adolescent to present one additional point on the behavioral disorder scale was 2.04 (95%CI: 1.53-2.71). Alcohol consumption, drug use, and suffering bullying were associated with higher scores on the behavioral disorder scale. The findings also showed that the factors associated with behavioral disorder showed a strong interrelationship between health behaviors in adolescence.     

Early health-related behaviours and their impact on later life chances: evidence from the US

This paper uses evidence from the US to examine the impact of adolescent illegal consumption and violent behaviour on later life chances. Specifically, we look at the effect of such behaviour by young men in late adolescence on productivity and household formation 10 years on. We find that alcohol and soft drug consumption have no harmful effects on economic prospects in later life. In contrast, hard drug consumption and violent behaviour in adolescence are both associated with lower productivity even by the time the individuals are in their late twenties. These effects are substantial and affect earnings levels and earnings growth. These results are robust to the inclusion of a rich set of additional controls measuring aspects of the individuals' backgrounds. However, we find no evidence of any of these behaviours significantly affecting household formation. © 1998 John Wiley & Sons, Ltd.     

HIV vaccine candidates generate in vitro T cell response to putative epitopes in Chinese-origin rhesus macaques

The Indian rhesus macaque is the established animal model for HIV infection and vaccine research. Growing evidence suggests that the more readily available Chinese rhesus macaque may be a more relevant option. As increasing numbers of novel Chinese rhesus MHC alleles are reported, we decided to explore potential HIV vaccine epitopes in this model. We immunized forty Chinese rhesus macaques with three different HIV vaccine candidates either individually or following a prime/boost strategy. We used ELISPOT to measure immune response in vitro to HIV-1 p24C and HIV-1 gp160 peptide libraries. We identified five putative epitopes with associations to HLA-I alleles including HLA*B-2705 and HLA-B*5101 (associated with slow disease progression and low viral set point) and HLA-B*18 (associated with rapid disease progression and high viral set point). This suggests the possible use of Chinese rhesus macaques to model different disease progressions. We also explored the use of fusion proteins as stimulators in ELISPOT assays. While PBMCs from 6 monkeys responded to peptide stimulation, PBMCs from 28 monkeys responded to the anthrax lethal factor fusion proteins LFn p24C and/or LFn gp140C. Our results support the use of Chinese rhesus macaques in HIV vaccine studies.     

Adolescent alcohol initiation: A review of psychosocial risk factors

Longitudinal research studies focused on alcohol use initiation in adolescence were reviewed to determine which variables function as antecedent predictors or risk factors. Only studies that focused on time-1 abstainers were included. Classes of risk factors examined include sociodemographic, family, peer, personality, and behavioral variables. The most consistent antecedent risk factors for starting to drink in adolescence were parental and peer approval and models for drinking and drug use as well as adolescents’ own prior involvement in delinquent behavior. There was little evidence for gender differences in risk factors for alcohol use initiation. Secondary analyses of existing longitudinal data sets are encouraged to examine whether there are ethnic/racial differences in the risk factors for starting to drink and to establish those factors that serve a protective or buffering function, delaying onset of alcohol use in adolescence.     

The Enduring Impact of Parents’ Monitoring,Warmth, Expectancies,and Alcohol Use on Their Children’s Future Binge Drinking and Arrests: a Longitudinal Analysis

Binge drinking is associated with many health and financial costs and is linked to risks of legal consequences. As alcohol use typically is initiated during adolescence, the current study assessed the relationship between parental behaviors and strategies in forecasting adolescents’ likelihood of binge drinking and later arrest. Restricted data from waves I–IV of the National Longitudinal Study of Adolescent Health were used to assess hypotheses. A weighted path analytic model (N?=?9421) provided a multifaceted picture of variables linked to later antisocial behavior. Low parental monitoring, low parental warmth, parent alcohol use, and parent expectancies regarding their children’s alcohol use were associated with higher incidence of adolescent binge drinking. In turn, low monitoring, low warmth, parent alcohol use, parent expectancies, and underage consumption were associated with binge drinking in early adulthood. Binge drinking during both adolescence and young adulthood were predictive of respondents’ likelihood of arrest 8–14 years later. Findings demonstrated the substantial, enduring effects of parental behaviors on child alcohol-related actions and have implications for parent-targeted interventions designed to reduce excessive alcohol consumption. They suggest campaigns focus on parenting strategies that involve setting effective and strict alcohol-related rules and guidelines, while maintaining a warm and supportive family environment.     

Heterogeneous Friendship Affiliation, Problem Behaviors, and Emotional Outcomes among High-Risk Adolescents

Adolescent friendship groups are often heterogeneous and thus involve exposure to both deviant and nondeviant influences. This longitudinal study examined whether the addition of nondeviant peer influences in early high school protected against the negative socialization effects of deviant affiliation on both concurrent and future smoking, alcohol problems, and depressive symptomatology. Adolescents (9th and 10th grade students, N?=?1,128) completed self-report questionnaires at both a baseline and 24-month assessment. Nondeviant affiliation consistently reduced the effects of deviant influences on smoking and alcohol problems but not on depressive symptoms. Findings reinforce the complexity of adolescent friendship influences and the notion that distinct mechanisms may drive the associations between deviant affiliations and behavioral and emotional outcomes throughout adolescence. Implications for prevention are also discussed.     

The risks for late adolescence of early adolescent marijuana use.

OBJECTIVES: The purpose of this study was to assess the relation of early adolescent marijuana use to late adolescent problem behaviors, drug-related attitudes, drug problems, and sibling and peer problem behavior. METHODS: African American (n = 627) and Puerto Rican (n = 555) youths completed questionnaires in their classrooms initially and were individually interviewed 5 years later. Logistic regression analysis estimated increases in the risk of behaviors or attitudes in late adolescence associated with more frequent marijuana use in early adolescence. RESULTS: Early adolescent marijuana use increased the risk in late adolescence of not graduating from high school; delinquency; having multiple sexual partners; not always using condoms; perceiving drugs as not harmful; having problems with cigarettes, alcohol, and marijuana; and having more friends who exhibit deviant behavior. These relations were maintained with controls for age, sex, ethnicity, and, when available, earlier psychosocial measures. CONCLUSIONS: Early adolescent marijuana use is related to later adolescent problems that limit the acquisition of skills necessary for employment and heighten the risks of contracting HIV and abusing legal and illegal substances. Hence, assessments of and treatments for adolescent marijuana use need to be incorporated in clinical practice.     

Suicidality, depression, and alcohol use among adolescents: a review of empirical findings

Suicide is a serious health problem as it is currently the third leading cause of death for teenagers between the ages of 15 and 24 years. Depression, which is also a serious problem for adolescents, is the most significant biological and psychological risk factor for teen suicide. Alcohol use remains extremely widespread among today's teenagers and is related to both suicidality and depression. Suicidality refers to the occurrence of suicidal thoughts or suicidal behavior. The consensus in empirical research is that mental disorders and substance abuse are the most important risk factors in both attempted and completed adolescent suicide. Therefore, it is incumbent upon researchers to identify the factors that can lead to their prevention among today's youth. This review compiles the existing literature on suicidality, depression, and alcohol use among adolescents spanning over the past 15 years. Both Problem Behavior Theory and Stress-coping Theory can explain the relationships among suicidality, depression and alcohol use. The prevention of suicidality is critical, especially during the early school years, when it is associated with depression and alcohol use. Suicidality, depression and alcohol use are three phenomenon that noticeably increase in adolescence marking this time period as an ideal opportunity for prevention efforts to commence. Future empirical work is needed that will further assess the impact of adolescent depression and alcohol use on suicidality. In sum, this review of empirical research highlights critical results and limitations, as well as indicates a need for continued efforts in preventing suicidality, depression, and alcohol use among adolescents.