Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study.

BACKGROUND: Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset. METHODS: PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models. RESULTS: Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence. CONCLUSIONS: PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.

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.

Personality and peer groups in adolescence: Reciprocal associations and shared genetic and environmental influences.

OBJECTIVE: Peer groups represent a critical developmental context in adolescence, and there are many well-documented associations between personality and peer behavior at this age. However, the precise nature and direction of these associations are difficult to determine as youth both select into, and are influenced by, their peers. METHOD: We thus examined the phenotypic, genetic, and environmental links between antisocial and prosocial peer characteristics and several personality traits from middle childhood to late adolescence (ages 11, 14, and 17 years) in a longitudinal twin sample (N = 3762) using teacher ratings of personality and self-reports of peer characteristics. RESULTS: Less adaptive trait profiles (i.e., high negative emotionality, low conscientiousness, and low agreeableness) were associated with more antisocial and fewer prosocial peer characteristics across time. Associations between personality traits related to emotionality (negative emotionality and extraversion) and peer behavior were largely attributable to shared genetic influences, while associations between personality traits related to behavioral control (conscientiousness and agreeableness) and peer behavior were due to overlapping genetic and shared environmental influences. CONCLUSIONS: Overall, results suggest a set of environmental presses that push youth toward both behavioral undercontrol and antisocial peer affiliations, making the identification of such influences and their relative importance a critical avenue of future work.

Differentiated nomological networks of internalizing, externalizing, and the general factor of psychopathology ('p factor') in emerging adolescence in the ABCD study.

BACKGROUND: Structural models of psychopathology consistently identify internalizing (INT) and externalizing (EXT) specific factors as well as a superordinate factor that captures their shared variance, the p factor. Questions remain, however, about the meaning of these data-driven dimensions and the interpretability and distinguishability of the larger nomological networks in which they are embedded. METHODS: The sample consisted of 10 645 youth aged 9-10 years participating in the multisite Adolescent Brain and Cognitive Development (ABCD) Study. p, INT, and EXT were modeled using the parent-rated Child Behavior Checklist (CBCL). Patterns of associations were examined with variables drawn from diverse domains including demographics, psychopathology, temperament, family history of substance use and psychopathology, school and family environment, and cognitive ability, using instruments based on youth-, parent-, and teacher-report, and behavioral task performance. RESULTS: p exhibited a broad pattern of statistically significant associations with risk variables across all domains assessed, including temperament, neurocognition, and social adversity. The specific factors exhibited more domain-specific patterns of associations, with INT exhibiting greater fear/distress and EXT exhibiting greater impulsivity. CONCLUSIONS: In this largest study of hierarchical models of psychopathology to date, we found that p, INT, and EXT exhibit well-differentiated nomological networks that are interpretable in terms of neurocognition, impulsivity, fear/distress, and social adversity. These networks were, in contrast, obscured when relying on the a priori Internalizing and Externalizing dimensions of the CBCL scales. Our findings add to the evidence for the validity of p, INT, and EXT as theoretically and empirically meaningful broad psychopathology liabilities.

Illuminating the origins of the intergenerational transmission of psychopathology with a novel genetically informed design.

Although it is well known that parental depression is transmitted within families across generations, the etiology of this transmission remains unclear. Our goal was to develop a novel study design capable of explicitly examining the etiologic sources of intergenerational transmission. We specifically leveraged naturally-occurring variations in genetic relatedness between parents and their adolescent children in the 720 families participating in the Nonshared Environment in Adolescent Development (NEAD) study, 58.5% of which included a rearing stepparent (nearly always a stepfather). Results pointed squarely to the environmental transmission of psychopathology between fathers and children. Paternal depression was associated with adolescent depression and adolescent behavior problems (i.e., antisocial behavior, headstrong behavior, and attention problems) regardless of whether or not fathers and their children were genetically related. Moreover, these associations persisted to a subset of "blended" families in which the father was biologically related to one participating child but not to the other, and appeared to be mediated via father-child conflict. Such findings are not only fully consistent with the environmental transmission of psychopathology across generations, but also add to extant evidence that parent-child conflict is a robust and at least partially environmental predictor of adolescent psychopathology.

Twin Differences in Harsh Parenting Predict Youth's Antisocial Behavior.

In the current study, we leveraged differences within twin pairs to examine whether harsh parenting is associated with children's antisocial behavior via environmental (vs. genetic) transmission. We examined two independent samples from the Michigan State University Twin Registry. Our primary sample contained 1,030 families (2,060 twin children; 49% female; 6-10 years old) oversampled for exposure to disadvantage. Our replication sample included 240 families (480 twin children; 50% female; 6-15 years old). Co-twin control analyses were conducted using a specification-curve framework, an exhaustive modeling approach in which all reasonable analytic specifications of the data are interrogated. Results revealed that, regardless of zygosity, the twin experiencing harsher parenting exhibited more antisocial behavior. These effects were robust across multiple operationalizations and informant reports of both harsh parenting and antisocial behavior with only a few exceptions. Results indicate that the association between harsh parenting and children's antisocial behavior is, to a large degree, environmental in origin.

Continuity and Change in the Genetic and Environmental Etiology of Youth Antisocial Behavior.

Trajectories of youth antisocial behavior (ASB) are characterized by both continuity and change. Twin studies have further indicated that genetic factors underlie continuity, while environmental exposures unique to each child in a given family underlie change. However, most behavioral genetic studies have examined continuity and change during relatively brief windows of development (e.g., during childhood but not into adolescence). It is unclear whether these findings would persist when ASB trajectories are examined across multiple stages of early development (i.e., from early childhood into emerging adulthood). Our study sought to fill this gap by examining participants assessed up to five times between the ages of 3 and 22 years using an accelerated longitudinal design in the Michigan State University Twin Registry (MSUTR). We specifically examined the etiologies of stability and change via growth curve modeling and a series of univariate and bivariate twin analyses. While participants exhibited moderate-to-high rank-order stability, mean levels of ASB decreased linearly with age. Genetic and nonshared environmental influences that were present in early childhood also contributed to both stability and change across development, while shared environmental contributions were negligible. In addition, genetic and nonshared environmental influences that were not yet present at the initial assessment contributed to change over time. Although ASB tended to decrease in frequency with age, participants who engaged in high levels of ASB during childhood generally continued to do so throughout development. Moreover, the genetic and nonshared environmental contributions to ASB early in development also shaped the magnitude of the decrease with age.

Adolescent Sexual Development and Peer Groups: Reciprocal Associations and Shared Genetic and Environmental Influences.

Peer groups influence the emergence of sexual behaviors in adolescence, but many details regarding the mechanisms underlying these effects have yet to be described. We examined the phenotypic, genetic, and environmental links between both antisocial and prosocial peer characteristics, and several sexual behaviors from middle childhood to late adolescence (ages 11, 14, and 17 years) using a longitudinal twin sample (N = 3762). Antisocial peers predicted greater engagement in both normative (e.g., dating) and non-normative (e.g., early sexual intercourse) sexual behaviors, while prosocial peers were associated with a lower likelihood of engaging in non-normative sexual behaviors. Reciprocal effects were also observed such that early sexual experiences were associated with a more antisocial and less prosocial peer groups later in adolescence. Behavioral genetic models indicated that most of the overlap between peer group characteristics and sexual behavior was due to shared environmental influences. That is, some features of the adolescent environment exert a press toward (or against) antisocial peers and sexual behaviors. Together, the results extend the existing literature by highlighting the ways through which peer affiliations are related to sexual development in adolescence.

Do neighborhood social processes moderate the etiology of youth conduct problems?

BACKGROUND: Prior work has robustly suggested that social processes in the neighborhood (i.e. informal social control, social cohesion, norms) influence child conduct problems (CP) and related outcomes, but has yet to consider how these community-level influences interact with individual-level genetic risk for CP. The current study sought to do just this, evaluating neighborhood-level social processes as etiologic moderators of child CP for the first time. METHODS: We made use of two nested samples of child and adolescent twins within the Michigan State University Twin Registry (MSUTR): 5649 families who participated in in the Michigan Twins Project (MTP) and 1013 families who participated in the Twin Study of Behavioral and Emotional Development (TBED-C). The neighborhood social processes of informal social control, social cohesion, and norms were assessed using neighborhood sampling techniques, in which residents of each twin family's neighborhood reported on the social processes in their neighborhood. Standard biometric GxE analyses evaluated the extent to which they moderated the etiology of CP. RESULTS: The 'no moderation' model provided the best fit to the data in nearly all cases, arguing against neighborhood social processes as etiologic moderators of youth CP. CONCLUSIONS: The neighborhood social processes evaluated here do not appear to exert their effects on child CP via etiologic moderation. The documented links between neighborhood social processes and child CP are thus likely to reflect a different etiologic process. Possibilities include environmental main effects of neighborhood social processes on child CP, or genotype-environment correlations.

Sexual Development in Adolescence: An Examination of Genetic and Environmental Influences.

Sexual development entails many experiences and is a major feature of adolescence. Most relevant behavioral genetic studies, however, focus primarily on sexual behaviors associated with health risks. We took a more normative, developmental perspective by examining genetic and environmental influences on five sexual behaviors ranging from dating to pregnancy in middle (Mage  = 14.90 years) and late adolescence (Mage  = 17.85 years) in a sample of twins (N = 3,762). Overall, behaviors that are more common and socially sanctioned (e.g., dating) were more heritable than behaviors that are less common and socially acceptable (e.g., sexual intercourse). That the etiology of different sexual behaviors is tied to their normativeness highlights the importance of considering the broader developmental context when studying sexual development.