Deviance proneness models propose a multi-level interplay in which transactions among genetic, individual, and family risk factors place children at increased risk for substance use. We examined bidirectional transactions between impulsivity and family conflict from middle childhood to adolescence and their contributions to substance use in adolescence and emerging adulthood (n = 380). Moreover, we examined children’s, mothers’ and fathers’ polygenic risk scores for behavioral undercontrol, and mothers’ and fathers’ interparental conflict and substance disorder diagnoses as predictors of these transactions. Results support a developmental cascade model in which children’s polygenic risk scores predicted greater impulsivity in middle childhood. Impulsivity in middle childhood predicted greater family conflict in late childhood, which in turn predicted greater impulsivity in late adolescence. Adolescent impulsivity subsequently predicted greater substance use in emerging adulthood. Results are discussed with respect to evocative genotype-environment correlations within developmental cascades and applications to prevention efforts.

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.

Effortful control is associated with fewer antisocial-aggressive behaviors (AAB) and depressive symptoms (DEP), but impulsivity may moderate these relations. However, few researchers have considered the effects of AAB-DEP co-occurrence. A multi-informant, multi-method approach assessed 5–10 year olds’ effortful control and impulsivity and, 5–6 years later, their AAB and DEP (N=474). Participants were non-Hispanic Caucasian (59.2%) or Hispanic (27.9%) from a southwestern U.S. metropolitan area. Low effortful control predicted pure AAB. Low effortful control and low impulsivity predicted pure DEP and co-occurring AAB-DEP. An effortful control-by-impulsivity-by-age interaction predicted pure AAB and co-occurring AAB-DEP. For older adolescents, lower effortful control predicted more symptoms only at average and high impulsivity. Results highlight multiple pathways to pure DEP vs. pure AAB or co-occurring AAB-DEP.

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.

This study examined the interplay between the influence of peers who promote alcohol use and μ-opioid receptor M1 (OPRM1) genetic variation in the intergenerational transmission of alcohol use disorder (AUD) symptoms while separating the “traitlike” components of AUD symptoms from their age-specific manifestations at three ages from emerging adulthood (17–23 years) to adulthood (29–40 years). The results for males were consistent with genetically influenced peer selection mechanisms as mediators of parent alcoholism effects. Male children of alcoholics were less likely to be carriers of the G allele in single nucleotide polymorphism A118G (rs1799971), and those who were homozygous for the A allele were more likely to affiliate with alcohol use promoting peers who increased the risk for AUD symptoms at all ages. There was evidence for women of an interaction between OPRM1 variation and peer affiliations but only at the earliest age band. Peer influences had stronger effects among women who were G-carriers. These results illustrate the complex ways in which the interplay between influences at multiple levels of analysis can underlie the intergenerational transmission of alcohol disorders as well as the importance of considering age and gender differences in these pathways.

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 selfregulation 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 selfregulation might be separate, transdiagnostic risk factors for several types of psychopathology.

Conduct problems, alcohol problems and hyperactive–inattentive symptoms co-occur at a high rate and are heritable in adolescence. The γ-aminobutyric acid A receptor, α2 gene (GABRA2) is associated with a broad spectrum of externalizing problems and disinhibitory-related traits. The current study tested whether two important forms of disinhibition in adolescence, impulsivity and sensation seeking, mediated the effects of GABRA2 on hyperactive–inattentive symptoms, conduct problems, and alcohol problems. Participants were assessed at two waves (11–17 and 12–18 years old; N = 292). Analyses used the GABRA2 SNP, rs279858, which tags the two complementary (yin–yang) GABRA2 haplotypes. Multiple informants reported on adolescents’ impulsivity and sensation seeking and adolescents self-reported their hyperactive–inattentive symptoms, conduct problems and lifetime alcohol problems. Impulsivity mediated the effect of GABRA2 on alcohol problems, hyperactive–inattentive symptoms, and conduct problems, whereas sensation seeking mediated the effect of GABRA2 on alcohol problems (AA/AG geno-types conferred risk). GABRA2 directly predicted adolescent alcohol problems, but the GG genotype conferred risk. Results suggest that there may be multiple pathways of risk from GABRA2 to adolescent externalizing problems, and suggest important avenues for future research.

Serotonin (5-HT) functioning is associated with alcohol problems. However, the mechanisms underlying this association remain unclear. The current study tested whether five separate dimensions of impulsivity (UPPS-P) mediated the relation between a polygenic score indexing 5-HT functioning and alcohol problems and whether any of these paths were moderated by age. Results showed that a 5-HT polygenic score predicted alcohol problems indirectly through negative urgency, but not any other facet of impulsivity. The 5-HT polygenic score also directly predicted alcohol problems. No age moderation was found. Findings suggest that negative urgency might be one important mechanism underlying the relation between genetically-influenced 5-HT functioning and alcohol problems. However, genetically-influenced 5-HT functioning likely influences alcohol problems through additional mechanisms. More broadly, results suggest that the previously observed transdiagnostic nature of 5-HT functioning on diverse types of psychopathology might be, in part, explained by its effect on negative urgency.