Pathways to substance use: Examining conduct problems and parenting behaviors from preschool to adolescence.

While many studies have identified risk and protective factors of substance use (SU), few have assessed the reciprocal associations of child conduct problems (CP) and parenting practices and behaviors in the prediction of SU across development. A greater understanding of how these factors relate over time is needed to improve the timing of targeted prevention efforts. This study examined how child CP, parenting behaviors, and parents' own antisocial behavior relate from preschool to adolescence and eventuate in SU. Participants included 706 youth (70.6% male; 89.7% white) enrolled in the Michigan Longitudinal Study. Data from waves 1 (ages 3-5), 2 (ages 6-8), 3 (ages 9-11), 4 (ages 12-14), and 5 (ages 15-17) were included. A random intercept cross-lagged panel model (RI-CLPM) examined reciprocal associations between parenting practices, parents' antisocial behavior, and child CP over time (waves 1-4) and how these factors contribute to adolescent alcohol, cigarette, and marijuana use (wave 5). At the within-person level, negative parenting and parents' own antisocial behavior had a strong influence in late childhood/early adolescence. Only child CP emerged as a significant predictor of SU. Results highlight the importance of early intervention and the potential influence of parenting and child factors throughout development in the prevention of SU.

Individual differences in the development of youth externalizing problems predict a broad range of adult psychosocial outcomes.

This study examined how youth aggressive and delinquent externalizing problem behaviors across childhood and adolescence are connected to consequential psychosocial life outcomes in adulthood. Using data from a longitudinal, high-risk sample (N = 1069) that assessed children and their parents regularly from early childhood (ages 3-5) through adulthood, multilevel growth factors of externalizing behaviors were used to predict adult outcomes (age 24-31), providing a sense of how externalizing problems across development were related to these outcomes via maternal, paternal, teacher, and child report. Findings indicated strong support for the lasting connections between youth externalizing problems with later educational attainment and legal difficulties, spanning informants and enduring beyond other meaningful contributors (i.e., child sex, cognitive ability, parental income and education, parental mental health and relationship quality). Some support was also found, although less consistently, linking externalizing problems and later alcohol use as well as romantic relationship quality. Delinquent/rule-breaking behaviors were often stronger predictors of later outcomes than aggressive behaviors. Taken together, these results indicate the importance of the role youth externalizing behaviors have in adult psychosocial functioning one to two decades later.

Adverse childhood experiences, sleep problems, low self-control, and adolescent delinquency: A longitudinal serial mediation analysis.

Several studies link adverse childhood experiences (ACEs) to delinquency. Yet, developmental sequalae accounting for this association remain unclear, with previous research limited by cross-sectional research designs and investigations of singular mediating processes. To redress these shortcomings, this study examines the longitudinal association between ACEs and delinquency as mediated by both sleep problems and low self-control, two factors which past research implicates as potentially important for understanding how ACEs contribute to antisocial behavior. Data collected from 480 adolescents (71.3% boys; 86.3% White) and their parents participating in the Michigan Longitudinal Study was used to conduct a serial mediation analysis. The association between ACEs (prior to age 11) and delinquency in late adolescence was found to operate indirectly via sleep problems in early adolescence and low self-control in middle adolescence. Nonetheless, a direct association between ACEs and later delinquency remained. Pathways through which ACEs contribute to later delinquency are complex and multiply determined. Findings indicate that early behavioral interventions, including improving sleep and self-control, could reduce later delinquency. Still, more research is needed to identify additional avenues through which the ACEs-delinquency association unfolds across development.

Exposure to Parental Alcohol Use Is Associated with Adolescent Drinking Even When Accounting for Alcohol Exposure of Best Friend and Peers.

AIMS: To further disentangle the role of exposure to drinking of role models (parents, peers, best friends) in the development of young adolescent alcohol use, the current study examined (a) whether parent's alcohol use exposure was associated with alcohol use outcomes among adolescents and (b) whether this association remained significant when including best friend and peer drinking exposure. METHODS: A longitudinal study followed 765 adolescents from the Netherlands over 3 years. Adolescents (45.6% male, Mage = 11.78, standard deviation = 0.49 at baseline) completed questionnaires every 6 months, resulting in seven measurement waves. Adolescents reported their own alcohol use and exposure to parental, best friend and peers drinking. RESULTS: Multilevel regression analyses indicated that parental alcohol use exposure was positively associated with a higher likelihood of adolescent alcohol use in the past 6 months, drinking in the last month and binge drinking in the last month. These associations remained significant when including exposure to peer and best friend's alcohol use, also when controlling for alcohol use at the previous timepoint (i.e. change in drinking). These associations were also consistent for boys and girls. CONCLUSIONS: Throughout early adolescence, parental alcohol exposure matters for their offspring's alcohol use, independently of whether peers or their best friend expose them to alcohol or not. Parental alcohol exposure should be considered in prevention efforts to further decrease the number of adolescents that engage in early alcohol use and binge drinking.

Subtypes of inhibitory and reward activation associated with substance use variation in adolescence: A latent profile analysis of brain imaging data.

The present study identified subgroups based on inhibitory and reward activation, two key neural functions involved in risk-taking behavior, and then tested the extent to which subgroup differences varied by age, sex, behavioral and familial risk, and substance use. Participants were 145 young adults (18-21 years old; 40.0% female) from the Michigan Longitudinal Study. Latent profile analysis (LPA) was used to establish subgroups using task-based brain activations. Demographic and substance use differences between subgroups were then examined in logistic regression analyses. Whole-brain task activations during a functional magnetic resonance imaging go/no-go task and monetary incentive delay task were used to identify beta weights as input for LPA modeling. A four-class model showed the best fit with the data. Subgroups were categorized as: (1) low inhibitory activation/moderate reward activation (39.7%), (2) moderate inhibitory activation/low reward activation (22.7%), (3) moderate inhibitory activation/high reward activation (25.2%), and (4) high inhibitory activation/high reward activation (12.4%). Compared with the other subgroups, Class 2 was older, less likely to have parental alcohol use disorder, and had less alcohol use. Class 4 was the youngest and had greater marijuana use. Classes 1 and 3 did not differ significantly from the other subgroups. These findings demonstrate that LPA applied to brain activations can be used to identify distinct neural profiles that may explain heterogeneity in substance use outcomes and may inform more targeted substance use prevention and intervention efforts.

Time-varying Effects of GABRG1 and Maladaptive Peer Behavior on Externalizing Behavior from Childhood to Adulthood: Testing Gene × Environment × Development Effects.

Engagement in externalizing behavior is problematic. Deviant peer affiliation increases risk for externalizing behavior. Yet, peer effects vary across individuals and may differ across genes. This study determines gene × environment × development interactions as they apply to externalizing behavior from childhood to adulthood. A sample (n = 687; 68% male, 90% White) of youth from the Michigan Longitudinal Study was assessed from ages 10 to 25. Interactions between γ-amino butyric acid type A receptor γ1 subunit (GABRG1; rs7683876, rs13120165) and maladaptive peer behavior on externalizing behavior were examined using time-varying effect modeling. The findings indicate a sequential risk gradient in the influence of maladaptive peer behavior on externalizing behavior depending on the number of G alleles during childhood through adulthood. Individuals with the GG genotype are most vulnerable to maladaptive peer influences, which results in greater externalizing behavior during late childhood through early adulthood.

Alcoholic family marital heterogeneity aggregates different child behavior problems both pre- and postseparation.

Children of alcoholics (COAs) are at risk for elevated internalizing and externalizing symptoms. Yet, little is known about the familial and behavioral adjustments of COAs following parental separation. Using an ecological-transactional framework, we examined how multiple risk factors contributed to the formation of different alcoholic family structures and how living in heterogeneous family structures affected COAs' behavioral problems. The Michigan Longitudinal Study, a multiwave study on initially intact alcoholic and control families with preschool-age children (n = 503), was used to evaluate outcomes of offspring, when families either remained intact or were separated when the child was aged 12-14. Alcoholic families who later transitioned into stepfamilies were characterized with higher paternal antisociality, marital aggression, and serious family crises than alcoholic families that remained intact. COAs in stepfamilies (but not in single-parent families) exhibited higher levels of internalizing and externalizing symptoms in preadolescence compared with those in alcoholic intact families, in part because of elevated behavioral risk at age 3. Structural equation modeling indicated that the aggregated risk of stepfamily residence directly related to COAs' internalizing and indirectly related to COAs' externalizing problems, partially mediated by family stressors. Findings suggest targeting COAs in separated families for early intervention.

Childhood adversity, externalizing behavior, and substance use in adolescence: Mediating effects of anterior cingulate cortex activation during inhibitory errors.

Childhood adversity can negatively impact development across various domains, including physical and mental health. Adverse childhood experiences have been linked to aggression and substance use; however, developmental pathways to explain these associations are not well characterized. Understanding early precursors to later problem behavior and substance use can inform preventive interventions. The aim of the current study was to examine neurobiological pathways through which childhood adversity may lead to early adolescent problem behavior and substance use in late adolescence by testing two prospective models. Our first model found that early adolescent externalizing behavior mediates the association between childhood adversity and alcohol, cigarette, and marijuana use in late adolescence. Our second model found that activation in the anterior cingulate cortex (ACC) during an inhibitory control task mediates the association between childhood adversity and early adolescent externalizing behavior, with lower ACC activation associated with higher levels of adversity and more externalizing behavior. Together these findings indicate that the path to substance use in late adolescence from childhood adversity may operate through lower functioning in the ACC related to inhibitory control and externalizing behavior. Early life stressors should be considered an integral component in the etiology and prevention of early and problematic substance use.

Oxytocin Genotype Moderates the Impact of Social Support on Psychiatric Distress in Alcohol-Dependent Patients.

AIMS: The social environment strongly influences individual mental health. Individuals with strong social support systems tend to experience higher levels of well-being, lower levels of psychological distress and exhibit fewer psychiatric symptoms. However, there is a significant degree of individual variability as to the extent to which social support is beneficial to overall mental health. From a neurobiological perspective, it is suggested that the social hormone, oxytocin, may moderate the favorable effects of social interaction. To explore this possibility, we evaluated oxytocin genotype, social support and psychological health in a group of individuals diagnosed with DSM-IV alcohol dependence. METHODS: The associations between OXT genotype, social support and psychological health were analyzed in data from 269 adults diagnosed with DSM-IV alcohol dependence (25% female) admitted into residential treatment programs and outpatient centers in Warsaw, Poland. RESULTS: In line with past observations, we noted that psychiatric distress scores were negatively correlated with social support. Extending these observations, we uncovered a significant moderating effect of OXT genotype (rs2740210) on the relationship between social support and psychiatric distress. While G carriers displayed the predicted negative relationship between social support and psychiatric distress, T homozygotes failed to exhibit such a relationship. CONCLUSION: Genetically driven variation in oxytocin system functioning may influence the degree to which the beneficial effects of social support are felt in this population. These results have direct clinical relevance as enhancing social engagement to improve mental health may prove to be a less effective strategy in some patients owing to intrinsic factors. SHORT SUMMARY: The associations between oxytocin genotype, social support, and psychological health were analyzed in data from 269 adults diagnosed with DSM-IV alcohol dependence. A significant moderating effect of OXT genotype (rs2740210) on the relationship between social support and psychiatric distress was detected.

Pathways to Youth Behavior: The Role of Genetic, Neural, and Behavioral Markers.

Neural and temperamental mechanisms through which a genetic risk marker in the γ-amino butyric acid α2 receptor subunit (GABRA2) impacts adolescent functioning were investigated. Participants (N = 80; 29 female) completed an emotional word task during functional magnetic resonance imaging. Behavioral control, negative emotionality, and resiliency temperament constructs were assessed. Externalizing and internalizing problems were the outcomes. Those with the GABRA2 minor allele had reduced activation to positive words in the angular gyrus, middle temporal gyrus, and cerebellum, and to negative words in frontal, parietal, and occipital cortices. Reduced activation in the angular gyrus predicted greater negative emotionality and, in turn, elevated externalizing problems. Reduced activation in the inferior parietal cortex predicted greater resiliency and, in turn, low externalizing problems.

Brain Activity, Low Self-Control, and Delinquency: An fMRI Study of At-Risk Adolescents.

PURPOSE: A vast literature finds that low self-control is associated with a myriad of antisocial behaviors. Consequently, increasing attention has focused on the causes of low self-control. While criminologists have directed significant attention to studying its social causes, fewer studies have considered its neural bases. METHODS: We add to this nascent body of research by using data collected on an at-risk sample of adolescents participating in the ongoing Michigan Longitudinal Study. We examine the functioning of prefrontal and limbic regions of the brain during failed inhibitory control, assessed using the go/no-go task and functional magnetic resonance imaging, in relation to low self-control and self-reported delinquency. RESULTS: Results indicate that greater activation localized in the anterior cingulate cortex (ACC) during failed inhibitory control is negatively associated with low self-control. Moreover, the association between ACC activity and later delinquency is mediated through low self-control. CONCLUSIONS: Findings of this study demonstrate the utility of integrating neuroscientific and criminological perspectives on the causes of antisocial behavior. Concluding remarks address the theoretical and policy implications of the findings, as well as directions for future research.

A time-varying effect model for examining group differences in trajectories of zero-inflated count outcomes with applications in substance abuse research.

This study proposes a time-varying effect model for examining group differences in trajectories of zero-inflated count outcomes. The motivating example demonstrates that this zero-inflated Poisson model allows investigators to study group differences in different aspects of substance use (e.g., the probability of abstinence and the quantity of alcohol use) simultaneously. The simulation study shows that the accuracy of estimation of trajectory functions improves as the sample size increases; the accuracy under equal group sizes is only higher when the sample size is small (100). In terms of the performance of the hypothesis testing, the type I error rates are close to their corresponding significance levels under all settings. Furthermore, the power increases as the alternative hypothesis deviates more from the null hypothesis, and the rate of this increasing trend is higher when the sample size is larger. Moreover, the hypothesis test for the group difference in the zero component tends to be less powerful than the test for the group difference in the Poisson component. Copyright © 2016 John Wiley & Sons, Ltd.

Beyond risk: Prospective effects of GABA Receptor Subunit Alpha-2 (GABRA2) × Positive Peer Involvement on adolescent behavior.

Research on Gene × Environment interactions typically focuses on maladaptive contexts and outcomes. However, the same genetic factors may also impact susceptibility to positive social contexts, leading to adaptive behavior. This paper examines whether the GABA receptor subunit alpha-2 (GABRA2) single nucleotide polymorphism rs279858 moderates the influence of positive peer affiliation on externalizing behavior and various forms of competence. Regions of significance were calculated to determine whether the form of the interaction supported differential susceptibility (increased sensitivity to both low and high positive peer affiliation) or vantage sensitivity (increased sensitivity to high positive peer affiliation). It was hypothesized that those carrying the homozygous minor allele (GG) would be more susceptible to peer effects. A sample (n = 300) of primarily male (69.7%) and White (93.0%) adolescents from the Michigan Longitudinal Study was assessed from ages 12 to 17. There was evidence for prospective Gene × Environment interactions in three of the four models. At low levels of positive peer involvement, those with the GG genotype were rated as having fewer adaptive outcomes, while at high levels they were rated as having greater adaptive outcomes. This supports differential susceptibility. Conceptualizing GABRA2 variants as purely risk factors may be inaccurate. Genetic differences in susceptibility to adaptive environmental exposures warrants further investigation.

Striatal dopaminergic reward response relates to age of first drunkenness and feedback response in at-risk youth.

Dopamine receptor concentrations, primarily in the striatum, are hypothesized to contribute to a developmental imbalance between subcortical and prefrontal control systems in emerging adulthood potentially biasing motivation and increasing risky behaviors. Positron emission tomography studies have found significant reductions in striatal dopamine D2 receptors, and blunted amphetamine-induced dopamine release, in substance users compared with healthy controls. Extant literature is limited and inconsistent concerning vulnerability associated with having a family history of substance abuse (FH+). Some studies have reported familial liability associated with higher dopamine receptor levels, reduced dopamine response to stimulant challenges and decreased response to oral alcohol. However, other reports have failed to find group differences based on family history. We explored the interaction of familial liability and behavioral risk with multi-modal molecular and neural imaging of the dopaminergic system. Forty-four young adult male subjects performed monetary incentive delay tasks during both [11 C]raclopride positron emission tomography and functional magnetic resonance imaging scans. FH+ subjects were identified as low (n = 24) or high risk (n = 9) based on early initiation of drunkenness. FH+ high-risk subjects exhibited heightened striatal dopamine response to monetary reward but did not differ in neural activations compared with FH+ low risk subjects and controls with no familial loading (n = 11). Across all subjects, a negative relationship was found between dopamine release and age of first drunkenness and a positive relationship with neural response to reward receipt. These results suggest that in at-risk individuals, higher dopamine transmission associated with monetary reward may represent a particularly useful neurobiological phenotype.

BOYS, EARLY RISK FACTORS FOR ALCOHOL PROBLEMS, AND THE DEVELOPMENT OF THE SELF: AN INTERCONNECTED MATRIX.

Alcohol-use disorders are a major public health issue worldwide. Although drinking and problematic alcohol use usually begins during adolescence, developmental origins of the disorder can be traced back to infancy and early childhood. Identification of early risk factors is essential to understanding developmental origins. Using data from the Michigan Longitudinal Study, an ongoing, prospective, high-risk family study, this article summarizes findings of family context and functioning of both children and parents. We draw attention to the development of the self, an understudied aspect of very young children being reared in alcoholic families that exacerbates exposure to high childhood adverse experiences. We also provide evidence demonstrating that young boys are embedded in a dynamic system of genes, epigenetic processes, brain organization, family dynamics, peers, community, and culture that strengthens risky developmental pathways if nothing is done to intervene during infancy and early childhood.

Sleep mediates the link between resiliency and behavioural problems in children at high and low risk for alcoholism.

Children of alcoholic parents are at greater risk for developing substance use problems. Having a parent with any mental illness increases the risk for sleep disorders in children. Using actigraphy, this study characterized sleep in children of alcoholics and community controls over a period of 1 week. This study further examined whether sleep characteristics of the children mediated the relationship between self-regulation indices (i.e. undercontrol and resiliency) and outcome measures of function (e.g. problem behaviours and perceived conflict at home). Eighty-two children (53 boys, 29 girls, 7.2-13.0 years old) were recruited from the ongoing Michigan Longitudinal Study. Seventeen participants had no parental history of alcohol abuse or dependence family history negative (FH-), 43 had at least one parent who was a recovered alcoholic, and 22 had at least one parent who met diagnostic criteria within the past 3 years. Sleep was assessed with actigraphy and sleep diaries for 1 week, and combined with secondary analysis of data collected for the longitudinal study. FH- children had more objectively measured total sleep time. More total sleep time was associated with greater resiliency and behavioural control, fewer teacher-reported behavioural problems, and less child-reported conflict at home. Further, total sleep time partially mediated the relationship between resiliency and perceived conflict, and between resiliency and externalizing problems. These findings suggest that in high-risk homes, the opportunity to obtain sufficient sleep is reduced, and that insufficient sleep further exacerbates the effects of impaired dispositional self-regulatory capacity on behavioural and emotional regulation.

Longitudinal phenotypes for alcoholism: Heterogeneity of course, early identifiers, and life course correlates.

Alcoholism is a heterogeneous disorder; however, characterization of life-course variations in symptomatology is almost nonexistent, and developmentally early predictors of variations are very poorly characterized. In this study, the course of alcoholic symptomatology over 32 years is differentiated, and predictors and covariates of trajectory class membership are identified. A community sample of alcoholic and neighborhood matched control families, 332 men and 336 women, was recruited based on alcoholism in the men. Symptoms were assessed retrospectively at baseline (mean age = 32) back to age 15 and prospectively from baseline every 3 years for 15 years. Trajectory classes were established using growth mixture modeling. Men and women had very similarly shaped trajectory classes: developmentally limited (men: 29%, women: 42%), developmentally cumulative (men: 26%, women: 38%), young adult onset (men: 31%, women: 21%), and early onset severe (men: 13%). Three factors at age 15 predicted class membership: family history of alcoholism, age 15 symptoms, and level of childhood antisocial behavior. Numerous measures of drinking and other psychopathology were also associated with class membership. The findings suggest that clinical assessments can be crafted where the profile of current and historical information can predict not only severity of prognosis but also future moderation of symptoms and/or remission over intervals as long as decades.

Susceptibility effects of GABA receptor subunit alpha-2 (GABRA2) variants and parental monitoring on externalizing behavior trajectories: Risk and protection conveyed by the minor allele.

Understanding factors increasing susceptibility to social contexts and predicting psychopathology can help identify targets for prevention. Persistently high externalizing behavior in adolescence is predictive of psychopathology in adulthood. Parental monitoring predicts low externalizing behavior, yet youth likely vary in the degree to which they are affected by parents. Genetic variants of GABA receptor subunit alpha-2 (GABRA2) may increase susceptibility to parental monitoring, thus impacting externalizing trajectories. We had several objectives: (a) to determine whether GABRA2 (rs279827, rs279826, rs279858) moderates the relationship between a component of parental monitoring, parental knowledge, and externalizing trajectories; (b) to test the form of this interaction to assess whether GABRA2 variants reflect risk (diathesis-stress) or susceptibility (differential susceptibility) factors; and (c) to clarify GABRA2 associations on the development of problem behavior. This prospective study (N = 504) identified three externalizing trajectory classes (i.e., low, decreasing, and high) across adolescence. A GABRA2 × Parental Monitoring effect on class membership was observed, such that A-carriers were largely unaffected by parental monitoring, whereas class membership for those with the GG genotype was affected by parental monitoring. Findings support differential susceptibility in GABRA2.

Indirect effect of corticotropin-releasing hormone receptor 1 gene variation on negative emotionality and alcohol use via right ventrolateral prefrontal cortex.

Variations in the corticotropin-releasing hormone receptor 1 (CRHR1) gene have been found to interact with stress in modulating excessive alcohol consumption. However, the neural mechanisms through which CRHR1 influences this risk in humans is largely unknown. This study examined the influence of an intronic CRHR1 gene variant, rs110402, on brain responses to negative emotional words, negative emotional traits, and alcohol use in adolescents and young adults at high risk for alcoholism. Childhood stress was investigated as a potential moderator. Using functional magnetic resonance imaging, we found that a region in the right ventrolateral prefrontal cortex (rVLPFC) was more engaged during negative emotional word processing in G homozygotes than in A allele carriers (p(FWE corrected) < 0.01, N = 77). Moreover, an indirect effect of genotype on negative emotionality via rVLPFC activation (p < 0.05, N = 69) was observed, which was further moderated by childhood stress (p < 0.05, N = 63). Specifically, with low childhood stress, G homozygotes exhibited lower levels of negative emotionality associated with greater rVLPFC activation, suggesting that the rVLPFC is involved in reappraisal that neutralizes negative emotional responses. In addition, we found that genotype indirectly modulated excessive alcohol consumption (p < 0.05, N = 69). Specifically, G homozygotes showed greater rVLPFC activation and had lower levels of negative emotionality, which were associated with fewer binge-drinking days and fewer alcohol related problems. This work provides support for a model in which CRHR1 gene variation modulates the risk of problem drinking via an internalizing/negative affect pathway involving rVLPFC and reappraisal of negative emotion.

Rule breaking mediates the developmental association between GABRA2 and adolescent substance abuse.

BACKGROUND: This study's primary aim was to examine age-specific associations between GABRA2, rule breaking, problematic alcohol use, and substance abuse symptomatology. The secondary aim was to examine the extent to which rule breaking mediates the GABRA2-substance abuse relationship. METHODS: A sample (n = 518) of primarily male (70.9%) and White (88.8%) adolescents from the Michigan Longitudinal Study was assessed from ages 11-18. Age-specific effects of GABRA2 on rule breaking, problematic alcohol use, and substance abuse symptomatology were examined using nested path models. The role of rule breaking as a mediator in the association between GABRA2 and substance abuse outcomes was tested using prospective cross-lagged path models. RESULTS: GABRA2 is significantly (p < 0.05) associated with rule breaking in mid- to late-adolescence, but not substance abuse symptomatology across adolescence. GABRA2 effects on problematic alcohol use and substance abuse symptomatology operate largely (45.3% and 71.1%, respectively, p < 0.05) via rule breaking in midadolescence. CONCLUSIONS: GABRA2 represents an early risk factor for an externalizing pathway to the development of problematic alcohol and drug use.