A Polygenic Risk Score Enhances Risk Prediction for Adolescents' Antisocial Behavior over the Combined Effect of 22 Extra-familial, Familial, and Individual Risk Factors in the Context of the Family Check-Up.

Possessing informative tools to predict who is most at risk for antisocial behavior in adolescence is important to help identify families most in need of early intervention. Polygenic risk scores (PRSs) have been shown to predict antisocial behavior, but it remains unclear whether PRSs provide additional benefit above more conventional tools to early risk detection for antisocial behavior. This study examined the utility of a PRS in predicting adolescents' antisocial behavior after accounting for a broad index of children's contextual and individual risk factors for antisocial behavior. Participants were drawn from a longitudinal family-based prevention study (N = 463; Ncontrol = 224; 48.8% girls; 45.1% White; 30.2% Black; 12.7% Hispanic/Latino, 10.4% biracial; 0.2% Native American). Participants were recruited from US-based Women, Infants, and Children Nutritional Supplement programs. A risk tolerance PRS was created from a genome-wide association study. We created a robust measure capturing additive effects of 22 conventional measures of a risk of antisocial behavior assessed at child age 2 (before intervention). A latent variable capturing antisocial behavior (ages 10.5-16) was created. After accounting for intervention status and the conventional risk index, the risk tolerance PRS predicted independent variance in antisocial behavior. A PRS-by-conventional risk interaction showed that the conventional risk measure only predicted antisocial behavior at high levels of the PRS. Thus, the risk tolerance PRS provides unique predictive information above conventional screening tools and, when combined with them, identified a higher-risk subgroup of children. Integrating PRSs could facilitate risk identification and, ultimately, prevention screening, particularly in settings unable to serve all individuals in need.

Persistent attention-deficit/hyperactivity disorder predicts socially oriented, but not physical/physiologically oriented, alcohol problems in early adulthood.

BACKGROUND: Although individuals with histories of childhood attention-deficit/hyperactivity disorder (ADHD) report more alcohol-related problems in adulthood than those without ADHD, it is unknown whether there are group differences in certain types of alcohol problems. We tested whether the nature of alcohol problems differed for individuals with and without childhood ADHD, as well as adulthood-persistent ADHD, to facilitate a personalized medicine approach for alcohol problems in this high-risk group. METHODS: Data were drawn from a prospective, observational study. Children diagnosed with ADHD and demographically similar individuals without childhood ADHD were followed prospectively through young adulthood (N = 453; 87.6% male). ADHD symptom persistence was assessed using self-reports and parent reports. Alcohol problems and heavy drinking were assessed repeatedly from 18-30 years old to construct lifetime measures. RESULTS: Full-sample confirmatory factor analyses identified 5 alcohol problem "types:" interpersonal problems/risky behaviors, occupational/academic impairment, impaired control/treatment seeking, tolerance/withdrawal, and drinking to blackout. Latent class analyses of items within each type yielded the best fit for 3-class solutions for all sets of items except blackout drinking, for which 2 classes emerged. Children with ADHD were more likely than those without ADHD to belong to high-risk latent classes for interpersonal problems/risky behaviors, occupational/academic problems, and impaired control (the high-risk class that indexed treatment-seeking behavior). These effects were driven by individuals whose ADHD symptoms persisted into adulthood. Few group differences emerged for tolerance/withdrawal and blackout drinking, except that individuals with only childhood ADHD (no persistence) were more likely to belong to the low-risk groups than those with adulthood-persistent ADHD and without ADHD. CONCLUSIONS: Individuals with ADHD histories whose symptoms persist into adulthood may be more likely to experience socially oriented alcohol problems and impaired control/treatment seeking than individuals without an ADHD history and those with childhood ADHD only. Tailored alcohol prevention and treatment programs may benefit this high-risk population.

Early Childhood Trajectories of Conduct Problems and Hyperactivity/Attention Problems: Predicting Adolescent and Adult Antisocial Behavior and Internalizing Problems.

Although conduct problems (CP) and hyperactivity/attention problems (HAP) are thought to covary with regularity, few studies have traced the probability of co-occurring CP and HAP longitudinally, particularly beginning in the toddler period. Further, there is little research examining how early co-occurring trajectories of CP and HAP predict functioning across several domains through late adolescence and early adulthood. Using a cohort of 284 low-income boys, we examined whether separate developmental trajectories of overt CP and HAP symptomatology from ages 2 to 10 relate to violent behavior, established correlates of antisocial behavior, impulsivity, and internalizing problems in adolescence and early adulthood. Co-occurring trajectory patterns of CP and HAP from ages 2 to 10 were also investigated in relation to later maladjustment. Findings indicated that trajectories of CP beginning in early childhood were related to violent behavior in adolescence and adulthood, adolescent correlates of antisocial behavior (i.e., deviant talk with peers), and internalizing problems in adulthood. Early HAP trajectories were also related to later problem behaviors when considered in isolation. However, when examining trajectories of CP and HAP simultaneously, children with chronic CP + chronic HAP, but not HAP-only, were most at risk for multiple types of problem behaviors in adolescence and early adulthood, including violent behavior and depressive and anxiety symptoms. Thus, HAP symptomatology was no longer predictive of adolescent and adult functioning once co-occurring CP was accounted for. Findings extend prior research with older children of HAP and/or CP, highlighting the predictive value of trajectories of CP beginning in the toddler period.

Role of ADHD in the Co-Occurrence Between Heavy Alcohol Use and Depression Trajectories in Adulthood.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with greater heavy alcohol use and depressive symptoms in adulthood. Yet, few studies have investigated whether childhood ADHD predicts an increased association between heavy drinking and depression in adulthood when this co-occurrence becomes more common. We examined associations among heavy alcohol use and depression longitudinally from ages 21 to 29 and whether these associations differed for those with or without childhood ADHD, as well as for those with or without persistent ADHD in adulthood. METHODS: Data were from the Pittsburgh ADHD Longitudinal Study, a prospective cohort of children diagnosed with ADHD and demographically similar individuals without ADHD histories. ADHD symptoms in adulthood were self- and parent reported; depressive symptoms and frequency of drinking 5 or more drinks in a single drinking occasion were self-reported and measured at 5 time-points from ages 21 to 29. Depression and alcohol use were modeled in a multiple-group, parallel process longitudinal growth model. RESULTS: The slopes of heavy alcohol use and depression were significantly and positively associated from ages 25 to 29 but not at the younger ages. Although the strength of these associations did not differ by group (with or without ADHD, childhood or adulthood), the slopes of depression and heavy drinking at the older ages were highly variable and individuals with ADHD showed significantly faster growth in depression from ages 25 to 29. CONCLUSIONS: Due to the strengthening association between heavy drinking and depression for adults in their late 20s, and increasing depression for adults with ADHD histories, individuals with ADHD may be at greater risk for co-occurring depression and binge drinking. Negative reinforcement-related alcohol use may strengthen as these individuals age toward the fourth decade of life. More rigorous testing of this possibility is warranted.

Bifactor model of effortful control and impulsivity and their prospective prediction of ego resiliency.

OBJECTIVE: Children's effortful control and impulsivity are important predictors of the personality trait, ego resiliency (i.e., resiliency). Most researchers have not considered the fact that effortful control and impulsivity share substantial conceptual and empirical overlap, yet they also have been shown to be distinct. We tested a bifactor model of effortful control and impulsivity to characterize their shared and unique variance, the prospective prediction of resiliency by the factors of the bifactor model, and moderation by sex and age. METHOD: In a longitudinal study of children (N = 214; 76.5% non-Hispanic Caucasian, 12.2% Hispanic, 11.3% other race/ethnicity), parent- and teacher-reported effortful control and impulsivity, as well as behavioral measures of effortful control, were assessed on two occasions (T1: 4.5-8 years; T2: 6-10 years). Parent-reported resiliency was used as a covariate (T1) and the outcome (T3: 8-12 years). RESULTS: The bifactor model yielded a common effortful inhibitory control factor, pure attentional control factor, and pure impulsivity factor. Pure impulsivity and pure attentional control positively predicted resiliency, but only for girls. Effortful inhibitory control did not uniquely predict resiliency. CONCLUSION: Disentangling the shared and unique aspects of effortful control and impulsivity could clarify the roles they play in important outcomes, such as resiliency.

Serotonin functioning and adolescents' alcohol use: A genetically informed study examining mechanisms of risk.

The current study used data from two longitudinal samples to test whether self-regulation, depressive symptoms, and aggression/antisociality were mediators in the relation between a polygenic score indexing serotonin (5-HT) functioning and alcohol use in adolescence. The results from an independent genome-wide association study of 5-hydroxyindoleacetic acid in the cerebrospinal fluid were used to create 5-HT polygenic risk scores. Adolescents and/or parents reported on adolescents' self-regulation (Time 1), depressive symptoms (Time 2), aggression/antisociality (Time 2), and alcohol use (Time 3). The results showed that 5-HT polygenic risk did not predict self-regulation. However, adolescents with higher levels of 5-HT polygenic risk showed greater depression and aggression/antisociality. Adolescents' aggression/antisociality mediated the relation between 5-HT polygenic risk and later alcohol use. Deficits in self-regulation also predicted depression and aggression/antisociality, and indirectly predicted alcohol use through aggression/antisociality. Pathways to alcohol use were especially salient for males from families with low parental education in one of the two samples. The results provide insights into the longitudinal mechanisms underlying the relation between 5-HT functioning and alcohol use (i.e., earlier aggression/antisociality). There was no evidence that genetically based variation in 5-HT functioning predisposed individuals to deficits in self-regulation. Genetically based variation in 5-HT functioning and self-regulation might be separate, transdiagnostic risk factors for several types of psychopathology.

Affiliation with substance-using peers: Examining gene-environment correlations among parent monitoring, polygenic risk, and children's impulsivity.

Parental monitoring can buffer the effect of deviant peers on adolescents' substance use by reducing affiliation with substance-using peers. However, children's genetic predispositions may evoke poorer monitoring, contributing to negative child outcomes. We examined evocative genotype-environment correlations underlying children's genetic predisposition for behavioral undercontrol and parental monitoring in early adolescence via children's impulsivity in middle childhood, and the influence of parental monitoring on affiliation with substance-using peers a year and a half later (n = 359). Genetic predisposition for behavioral undercontrol was captured using a polygenic risk score, and a portion of passive rGE was controlled by including parents' polygenic risk scores. Children's polygenic risk predicted poorer parental monitoring via greater children's impulsivity, indicating evocative rGE, controlling for a portion of passive rGE. Poorer parental monitoring predicted greater children's affiliation with substance-using peers a year and a half later. Results are discussed with respect to gene-environment correlations within developmental cascades.

Roles of Response Inhibition and Gene-Environment Interplay in Pathways to Adolescents' Externalizing Problems.

This study used two waves of data to investigate pathways through which adolescents' response inhibition related to later externalizing problems. A polygenic risk score indexed genetic risk for poor response inhibition. Adolescents' performance on a response inhibition task mediated the relation between adolescents' polygenic risk scores and mother's inconsistent parenting (i.e., evocative rGE), even after controlling for mothers' genetic risk (i.e., passive rGE). Mothers' inconsistent parenting subsequently prospectively predicted adolescents' externalizing problems. Adolescents' response inhibition also prospectively predicted later externalizing behaviors. These findings were subgroup-specific, with greater risk for non-Hispanic Caucasian boys with substance-disordered parents. Results suggest that poor response inhibition may increase risk for adolescents' externalizing problems both directly and by evoking certain environmental conditions.

Testing the Relations Among Family Disorganization, Delay Discounting, and Adolescent Alcohol Use: A Genetically Informed Study.

BACKGROUND: Delay discounting is a potential etiological factor in adolescents' alcohol use, making it important to understand its antecedents. Family disorganization might contribute to delay discounting, but few studies have tested this relation. Moreover, because delay discounting is heritable, the effects of family disorganization on delay discounting might be moderated by adolescents' genetic risk for delay discounting. Thus, the current study examined the role of family disorganization, in interaction with genetic risk, in predicting adolescents' delay discounting and subsequent alcohol use. METHODS: Adolescents participated in 4 waves of data collection. Adolescents self-reported their family disorganization at T1, completed a delay discounting questionnaire at T3, and self-reported their alcohol use both at T2 (covariate) and T4 (outcome). Using results from an independent sample, we created a polygenic risk score consisting of dopaminergic genes to index genetic risk for delay discounting. RESULTS: Greater family disorganization predicted adolescents' greater delay discounting, but only for adolescents with low levels of genetic risk for delay discounting. Adolescents with high and mean levels of genetic risk for delay discounting showed elevated delay discounting regardless of their family's disorganization. Greater delay discounting prospectively predicted adolescents' greater alcohol use. Finally, the effects of family disorganization on adolescents' alcohol use were mediated through delay discounting, but only for adolescents with low levels of genetic risk. CONCLUSIONS: Results suggest multiple pathways to delay discounting. Although there are genetically influenced pathways to delay discounting, family disorganization might represent an environmental pathway to delay discounting (and subsequent alcohol use) for a subset of adolescents at low genetic risk. These findings reinforce the utility of family interventions for reducing adolescents' delay discounting and alcohol use, at least for a subgroup of adolescents. Because higher family organization did not buffer against delay discounting among adolescents with high genetic risk, future research should explore other early environmental influences that could protect these high-risk adolescents from developing these risky behaviors.

Role of temperament in early adolescent pure and co-occurring internalizing and externalizing problems using a bifactor model: Moderation by parenting and gender.

We contribute to the literature on the relations of temperament to externalizing and internalizing problems by considering parental emotional expressivity and child gender as moderators of such relations and examining prediction of pure and co-occurring problem behaviors during early to middle adolescence using bifactor models (which provide unique and continuous factors for pure and co-occurring internalizing and externalizing problems). Parents and teachers reported on children's (4.5- to 8-year-olds; N = 214) and early adolescents' (6 years later; N = 168) effortful control, impulsivity, anger, sadness, and problem behaviors. Parental emotional expressivity was measured observationally and with parents' self-reports. Early-adolescents' pure externalizing and co-occurring problems shared childhood and/or early-adolescent risk factors of low effortful control, high impulsivity, and high anger. Lower childhood and early-adolescent impulsivity and higher early-adolescent sadness predicted early-adolescents' pure internalizing. Childhood positive parental emotional expressivity more consistently related to early-adolescents' lower pure externalizing compared to co-occurring problems and pure internalizing. Lower effortful control predicted changes in externalizing (pure and co-occurring) over 6 years, but only when parental positive expressivity was low. Higher impulsivity predicted co-occurring problems only for boys. Findings highlight the probable complex developmental pathways to adolescent pure and co-occurring externalizing and internalizing problems.