Interactions Between Genetic, Prenatal Substance Use, Puberty, and Parenting are Less Important for Understanding Adolescents' Internalizing, Externalizing, and Substance Use than Developmental Cascades in Multifactorial Models.

This study tested interactions among puberty-related genetic risk, prenatal substance use, harsh discipline, and pubertal timing for the severity and directionality (i.e., differentiation) of externalizing and internalizing problems and adolescent substance use. This is a companion paper to Marceau et al. (2021) which examined the same influences in developmental cascade models. Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n = 4504 White boys, n = 4287 White girls assessed from the prenatal period through 18.5 years). We hypothesized generally that later predictors would strengthen the influence of puberty-related genetic risk, prenatal substance use exposure, and pubertal risk on psychopathology and substance use (two-way interactions), and that later predictors would strengthen the interactions of earlier influences on psychopathology and substance use (three-way interactions). Interactions were sparse. Although all fourteen interactions showed that later influences can exacerbate or trigger the effects of earlier ones, they often were not in the expected direction. The most robust moderator was parental discipline, and differing and synergistic effects of biological and socially-relevant aspects of puberty were found. In all, the influences examined here operate more robustly in developmental cascades than in interaction with each other for the development of psychopathology and transitions to substance use.

The role of fathers in child development from preconception to postnatal influences: Opportunities for the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) program.

A growing body of literature highlights the important role of paternal health and socioemotional characteristics in child development, from preconception through adolescence. Much of this research addresses the indirect effects of fathers, for instance, their influence on maternal behaviors during the prenatal period or via the relationship with their partner. However, emerging evidence also recognizes the direct role of paternal health and behavior for child health and adjustment across development. This critical review presents evidence of biological and sociocultural influences of fathers on preconception, prenatal, and postnatal contributions to child development. The National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) program incorporates in its central conceptualization the impact of fathers on family and child outcomes. This critical synthesis of the literature focuses on three specific child outcomes in the ECHO program: health outcomes (e.g., obesity), neurodevelopmental outcomes (e.g., emotional, behavioral, psychopathological development), and positive health. We highlight the unique insights gained from the literature to date and provide next steps for future studies on paternal influences.

Reliability of prospective and retrospective maternal reports of prenatal experiences.

BACKGROUND: Extant perinatal research utilizes retrospective reports on the prenatal environment, but there are limited data on the validity of retrospective data compared with prospective data. The current study examined the reliability of birth mothers' memory of prenatal stress and distress and perinatal risks at 6-months postpartum with maternal reports gathered across each trimester of pregnancy and explored whether recall varied with maternal socioeconomic status. METHODS: Surveys were collected from 34 pregnant women (M age = 29.14, SD = 5.06 years, 83% non-Hispanic White) on stress, distress, and pregnancy complications at 12(T1), 26(T2), and 38(T3) weeks of pregnancy, and at 6-month post-partum asking the same questions but specifically about the pregnancy. Cohen's kappa and Pearson's correlations were used to investigate maternal recall at post-partum with prospective reports at T1, T2, T3 and an average score of T1, T2, and T3. Correlations were also examined separately for those with high and relatively lower socioeconomic status. RESULTS: Birth mothers' recall was generally reliable. Retrospective reports were most strongly related to prospective reports in T1 for perceived stress, T1 and T3 for anxiety symptoms and exposure to toxins, but T3 for depressive symptoms. Recall of pregnancy complications best reflected the average score across trimesters (rather than specific trimesters). Women with higher socioeconomic status better recalled prenatal (di)stress, but women with relatively lower socioeconomic status better recalled exposure to toxins. CONCLUSION: This study provides support for utilizing retrospective reports of maternal prenatal experiences at 6-months post-partum, with implications for interpretation of specific recalled phenotypes.

Generalist genes and specialist environments for adolescent internalizing and externalizing problems: A test of severity and directionality.

The generalist genes specialist environment model, when applied to developmental psychopathology, predicts that genetic influences should explain variance that is shared across internalizing and externalizing problems, whereas environmental influences should explain variance that distinguishes the two overarching problem types. The present study is a direct test of this hypothesis, leveraging a sample of 708 twins and siblings (aged 10-18 years, 93% White) from the United States. Measures of severity of symptoms, regardless of type, and of directionality of symptoms - whether the adolescent tended to exhibit more externalizing or internalizing problems - were subjected to genetic (A), shared environmental (C), and nonshared environmental (E) (ACE) variance decompositions. As expected, severity of problems was under substantial genetic influence, but there were also significant shared and nonshared environmental influences. Contrary to the generalist genes specialist environment model, directionality of problem type was also under considerable genetic influence, with modest nonshared environmental influence. Findings corroborate existing evidence from other designs highlighting the role of familial influences (including generalist genes) in comorbidity of adolescent internalizing and externalizing problems, but suggest that the specialist environments hypothesis may not be the key factor in distinguishing problem type.

Father absence, age at menarche, and genetic confounding: A replication and extension using a polygenic score.

Father absence has a small but robust association with earlier age at menarche (AAM), likely reflecting both genetic confounding and an environmental influence on life history strategy development. Studies that have attempted to disambiguate genetic versus environmental contributions to this association have shown conflicting findings, though genomic-based studies have begun to establish the role of gene-environment interplay in the father absence/AAM literature. The purpose of this study was to replicate and extend prior genomic work using the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective longitudinal cohort study (N = 2,685), by (a) testing if an AAM polygenic score (PGS) could account for the father absence/AAM association, (b) replicating G×E research on lin-28 homolog B (LIN28B) variation and father absence, and (c) testing the G×E hypothesis using the PGS. Results showed that the PGS could not explain the father absence/AAM association and there was no interaction between father absence and the PGS. Findings using LIN28B largely replicated prior work that showed LIN28B variants predicted later AAM in father-present girls, but this AAM-delaying effect was absent or reversed in father-absent girls. Findings are discussed in terms genetic confounding, the unique biological role of LIN28B, and using PGSs for G×E tests.

Longitudinal associations between mother-child conflict and child internalizing problems in mid-childhood.

Several aspects of mother-child relationships are associated with children's internalizing problems. We examined longitudinal associations between mother-child conflict and children's internalizing problems in middle childhood. Specifically, we examined whether conflict and children's internalizing problems predict each other longitudinally in a sample of children from 3rd through 6th grade (N = 1,364) and their mothers using a cross-lagged panel model with random intercepts. In line with expectations, we found stable between-family differences in both mother-child conflict and children's internalizing problems. Contrary to expectations, we did not find that mother-child conflict and children's internalizing problems showed significant cross-lagged associations. However, mother-child conflict and children's internalizing problems had correlated errors at each wave, indicating that these two constructs covary with each other concurrently at multiple times across development, independent of stable between-family associations (i.e., as one increases, so does the other, and vice versa). The results of this study point to the importance of using statistical approaches that can disentangle between-family differences from within-family processes. In future studies, shorter time scales (e.g., weeks or months) may better capture dynamic associations between parent-child conflict and internalizing problems.

Intergenerational transmission of psychopathology: An examination of symptom severity and directionality.

The present study examined the intergenerational transmission of internalizing and externalizing symptom severity, which indexes comorbidity, and symptom directionality, which indicates differentiation toward externalizing versus internalizing problems. Data are from 854 male and female, same-sex adult twin pairs born between 1926 and 1971 (32-60 years old, M = 44.9 years, SD = 4.9 years) from the Twin and Offspring Study in Sweden and their adolescent offspring (11-22 years old, M = 15.7 years, SD = 2.4 years, 52% female). Children-of-twins models revealed additive (9%) and dominant (45%) genetic and nonshared environmental (47%) influences on twins' symptom severity, and additive genetic (39%) and nonshared environmental (61%) influences on twins' symptom directionality. Both comorbid problems and preponderance of symptoms of a particular - internalizing versus externalizing - spectrum were correlated across parent and child generations, although associations were modest especially for directionality (i.e., transmission of specific symptom type). By interpreting findings alongside a recent study of adolescent twins, we demonstrate that the intergenerational transmission of symptom severity and symptom directionality are both unlikely to be attributable to genetic transmission, are both likely to be influenced by direct phenotypic transmission and/or nonpassive rGE, and the intergenerational transmission of symptom severity is also likely to be influenced by passive rGE.

The roles of familial transmission and smoking during pregnancy on executive function skills: A sibling-comparison study.

This research examines maternal smoking during pregnancy and risk for poorer executive function in siblings discordant for exposure. Data (N = 173 families) were drawn from the Missouri Mothers and Their Children study, a sample, identified using birth records (years 1998-2005), in which mothers changed smoking behavior between two pregnancies (Child 1 [older sibling]: M age = 12.99; Child 2 [younger sibling]: M age = 10.19). A sibling comparison approach was used, providing a robust test for the association between maternal smoking during pregnancy and different aspects of executive function in early-mid adolescence. Results suggested within-family (i.e., potentially causal) associations between maternal smoking during pregnancy and one working memory task (visual working memory) and one response inhibition task (color-word interference), with increased exposure associated with decreased performance. Maternal smoking during pregnancy was not associated with stop-signal reaction time, cognitive flexibility/set-shifting, or auditory working memory. Initial within-family associations between maternal smoking during pregnancy and visual working memory as well as color-word interference were fully attenuated in a model including child and familial covariates. These findings indicate that exposure to maternal smoking during pregnancy may be associated with poorer performance on some, but not all skills assessed; however, familial transmission of risk for low executive function appears more important.

Adolescent substance use: Findings from a state-wide pilot parent education program.

BACKGROUND: Adolescent substance use has long been a top public health priority. In Indiana, concerning recent trends show high rates of youth alcohol consumption coupled with increasing use of opioids, synthetic marijuana, and over-the-counter drugs. Based on research indicating that parent-based prevention efforts may be a particularly effective way to target adolescent substance use, and in a direct effort to address Indiana's 2017 Strategic Plan to Address Substance Use, we conducted an applied research study targeting parents' knowledge regarding adolescent substance use in Indiana. METHODS: This community-based applied research study included: (i) a needs assessment of Indiana Extension Educators' concerns regarding adolescent substance use, (ii) creation and dissemination of an evidence-informed parent education program on adolescent substance use in collaboration with Purdue Extension (a key community stakeholder), and (iii) qualitative focus group discussions at the end of each program that assessed the challenges families face regarding adolescent substance use, the types of information and resources they wish they had, and the usefulness of our program. RESULTS: The needs assessment revealed that Indiana communities would most benefit from education regarding ways to spot and monitor substance use in teens, and strategies to communicate with teens about substance use. Additionally, Extension Educators thought that existing resources to tackle substance use largely did not match the needs of Indiana communities. Qualitative analysis of the focus group discussions across 8 pilot programs revealed five important themes: (1) The need for current, evidence-informed information regarding adolescent substance use among parents and youth-involved professionals in Indiana, (2) Concern regarding Indiana adolescents' ease of access to substances and lack of healthy recreational activities, (3) Communicating with teens about substance use is crucial but difficult to implement, (4) Indiana communities' need to prioritize funding for evidence-informed prevention programming, and (5) The need for community-based parent and caregiver support groups. CONCLUSIONS: Overall, the program was well-received and participants indicated that there was a strong need for this programming in their communities, but suggested collaborating with schools or similar local community stakeholders to increase attendance. Findings from this pilot study can inform future community-based adolescent substance use prevention efforts state-wide.

Interactions between Genetic, Prenatal, Cortisol, and Parenting Influences on Adolescent Substance Use and Frequency: A TRAILS Study.

INTRODUCTION: Dynamic relations between genetic, hormone, and pre- and postnatal environments are theorized as critically important for adolescent substance use but are rarely tested in multifactorial models. This study assessed the impact of interactions of genetic risk and cortisol reactivity with prenatal and parenting influences on both any and frequency of adolescent substance use. METHODS: Data are from the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective longitudinal, multi-rater study of 2,230 Dutch adolescents. Genetic risk was assessed via 3 substance-specific polygenic scores. Mothers retrospectively reported prenatal risk when adolescents were 11 years old. Adolescents rated their parents' warmth and hostility at age 11. Salivary cortisol reactivity was measured in response to a social stress task at age 16. Adolescents' self-reported cigarette, alcohol, and cannabis use frequency at age 16. RESULTS: A multivariate hurdle regression model showed that polygenic risk for smoking, alcohol, and cannabis predicted any use of each substance, respectively, but predicted more frequent use only for smoking. Blunted cortisol reactivity predicted any use and more frequent use for all 3 outcomes. There were 2 interactions: blunted cortisol reactivity exacerbated the association of polygenic risk with any smoking and the association of prenatal risk with any alcohol use. CONCLUSION: Polygenic risk seems of importance for early use but less so for frequency of use, whereas blunted cortisol reactivity was correlated with both. Blunted cortisol reactivity may also catalyze early risks for substance use, though to a limited degree. Gene-environment interactions play no role in the context of this multifactorial model.

Predictors and moderators of response to brief interventions among adolescents with risky alcohol and marijuana use.

Background:Brief interventions have shown promise in reducing adolescent alcohol and marijuana use. This manuscript presents a secondary analysis of a randomized trial that compared a brief parent motivational intervention (Family Check Up; FCU) to brief psychoeducation (PE) condition and found no effect of treatment condition on either binge drinking or marijuana use days. The current analyses explored whether the response to treatment may have varied as a function of six empirically-based baseline moderators and predictors: biological sex, age, race/ethnicity, mental health problems, parent-adolescent communication, and peer deviance. Methods: Data from the parent trial randomizing 102 parents to either the FCU (n = 51) or PE (n = 51) interventions were re-analyzed across four time points (baseline, 3-, 6-, and 12-months). Moderators and predictors were tested via a series of hierarchical linear models. Results: Parent-adolescent communication and peer deviance emerged as significant predictors of adolescent treatment response. Specifically, low-levels of parent-adolescent communication or peer deviance were associated with worse treatment response (i.e., significant increases in binge drinking days and marijuana use days) in the PE condition, but not in the FCU condition. Non-Hispanic Whites and girls had worse treatment response, regardless of treatment condition. Conclusions: The FCU condition appeared to mitigate risks of poor parent-adolescent communication and affiliation with deviant peers better than the PE condition. Clinical recommendations for decision-making around assignment to brief interventions are discussed.

Not Seeing Double: Discordance in Disease, Function, and Their Longitudinal Associations in Monozygotic Twins.

OBJECTIVE: Prior research on the causality and directionality between disease and functional limitations is ambiguous. The current study used longitudinal monozygotic twin data to test both directions linking disease burden and functional limitations in middle-aged and older adults, controlling for genetic and familial factors. We also examined potential moderation by psychological well-being. METHODS: The twin subsample from the first two waves of the longitudinal Midlife in the United States (MIDUS) study was used (wave 1, 1995-1996; wave 2, 2004-2006). Only monozygotic twins (n = 713) were included in analyses. In separate multilevel models, we examined disease burden at MIDUS 2 predicted by functional limitations at MIDUS 1 and MIDUS 2 functional limitations predicted by disease burden at MIDUS 1. RESULTS: Disease burden and functional limitations at MIDUS 2 varied substantially within families. There was no within-family association of earlier functional limitations with change in later disease burden (b = 0.40, p = .39), but there was a within-family association such that the twin with higher baseline disease burden had a greater increase in functional limitations than his/her co-twin (b = 0.06, p = .02). Well-being was not a moderator in either model. CONCLUSIONS: We found support for a potentially causal association between earlier disease burden and later increases in functional limitations, consistent with the Disablement Process Model. Sensitivity analyses confirm the detected within-family effect. Possible mechanisms linking disease burden and functional limitations are discussed as potential targets for future research.

Developmental Cascades from Polygenic and Prenatal Substance Use to Adolescent Substance Use: Leveraging Severity and Directionality of Externalizing and Internalizing Problems to Understand Pubertal and Harsh Discipline-Related Risk.

The current study leveraged the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n = 4504 White boys, n = 4287 White girls assessed from the prenatal period through 18.5 years of age) to test a developmental cascade from genetic and prenatal substance use through pubertal timing and parenting to the severity of (regardless of type) and directionality (i.e., differentiation) of externalizing and internalizing problems to adolescent substance use. Limited associations of early pubertal timing with substance use outcomes were only observable via symptom directionality, differently for girls and boys. For boys, more severe exposure to prenatal substance use influenced adolescent substance use progression via differentiation towards relatively more pure externalizing problems, but in girls the associations were largely direct. Severity and especially directionality (i.e., differentiation towards relatively more pure externalizing problems) were key intermediaries in developmental cascades from parental harsh discipline with substance use progressions for girls and boys.

Trajectories of early alcohol use milestones: Interrelations among initiation and progression.

BACKGROUND: Alcohol use shows age-graded patterning, with normative use progressing through characteristic milestones of escalating use or severity. Despite some knowledge about the timing of milestone attainment and sequencing across milestones, there is a gap in our understanding of the earliest stages of use. This study characterizes the timing, sequencing, and speed of progression through milestones beginning with the first sip of alcohol. METHODS: Sixth through eighth graders (N = 1023; 52% female; 76% White; M = 12.23 years old) completed web surveys through the end of high school. Participants reported on alcohol experiences including the first sip, full drink, consumption of 3+ drinks/occasion (heavy drinking), being drunk, and experiencing acute consequences, from which milestone age and speed of progression (duration) were calculated. Milestone prevalence, sequencing, and timing were characterized, and associations between age of attainment and speed of progression were examined. We also examined whether milestone timing and progression varied by sex and racial/ethnic group. RESULTS: Overall, milestones followed the expected ordering with the exception of heavy drinking (3+ drinks/occasion) and being drunk, which appear to index similar experiences. An earlier age of attainment was associated with an increased likelihood of attaining each of the milestones. In contrast, once a milestone was achieved, there was reduced risk of initiation of subsequent adjacent milestones for individuals with an earlier first sip and full drink, and earlier initiation was associated with a longer duration to subsequent milestones. Girls were more likely to attain all milestones than boys, but there was no sex difference in the age of attainment. In contrast, Hispanic youth reported earlier ages of initiation than White non-Hispanic youth, but the likelihood of attainment did not vary by race/ethnicity. Rapid progression was observed in females but did not vary by race/ethnicity. DISCUSSION: Risks associated with early drinking are complex, with little support for normative ordering of milestones beyond the first sip. Although early drinking is associated with an increased risk of subsequent drinking, it does not appear to place the drinker on an accelerated course to heavier use. A nuanced understanding of risks associated with milestone timing may inform intervention efforts.

The codevelopment of adolescents' and parents' anxiety and depression: Moderating influences of youth gender and psychophysiology.

METHODS: In a 2-year longitudinal study of 220 families, we examined how youth gender and adrenocortical and parasympathetic activity moderated reciprocal, bidirectional relations between parent and youth anxiety and depression problems. RESULTS: Maternal anxiety predicted subsequent youth anxiety and depression. Maternal depression predicted youth anxiety and, for daughters and youth with low adrenocortical reactivity, youth depression. Youth depression predicted maternal depression only for youth with high adrenocortical reactivity. There were no associations between paternal and youth psychopathology. DISCUSSION: Examining youth gender and psychophysiological characteristics that shape the nature of bidirectional influences may inform efforts to identify families at heightened risk for intergenerational transmission of psychopathology.

Disruptive Behavior in Siblings Discordant for Exposure to Maternal Smoking During Pregnancy: A Multi-rater Approach.

INTRODUCTION: Maternal smoking during pregnancy (SDP) is associated with disruptive behavior. However, there is debate whether the SDP-disruptive behavior association is a potentially causal pathway or rather a spurious effect confounded by shared genetic and environmental factors. AIMS AND METHODS: The Missouri Mothers and Their Children Study is a sibling comparison study that includes families (n = 173) selected for sibling pairs (aged 7-16 years) discordant for SDP. Critically, the sibling comparison design is used to disentangle the effects of SDP from familial confounds on disruptive behavior. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount of SDP). Multiple informants (parents and teachers) reported on disruptive behavior (i.e., DSM-IV semi-structured interview, the Child Behavior Checklist, and Teacher Report Form). RESULTS: The variability in disruptive behavior was primarily a function of within-family differences (66%-100%). Consistent with prior genetically informed approaches, the SDP-disruptive behavior association was primarily explained by familial confounds (genetic and environmental). However, when using a multi-rater approach (parents and teachers), results suggest a potentially causal effect of SDP on disruptive behavior (b = 0.09, SE = 0.04, p = 0.03). The potentially causal effect of SDP remained significant in sensitivity analyses. DISCUSSION: These findings suggest that familial confounding likely plays a complex role in the SDP-disruptive behavior association when examining both parent and teacher reports of behavior. Importantly, the current study highlights the importance of multiple raters, reflecting a more comprehensive measure of complex behaviors (e.g., disruptive behavior) to examine the teratogenic effects of SDP. IMPLICATIONS: Our study provides additional evidence that controlling for genetic and family factors is essential when examining the effect of SDP on later behavioral problems, as it explains a portion of the association between SDP and later behavioral problems. However, we found a significant association between SDP and disruptive behavior when using a multi-rater approach that capitalizes on both parent and teacher report, suggesting that parent and teacher ratings capture a unique perspective that is important to consider when examining SDP-behavior associations.

Co-occurring childhood maltreatment exposure and depressive symptoms in adulthood: Testing differential effects of stress dysregulation and perceived stress.

Objectives: Objectives were to explore: 1) the association between sub-groups with different multi-type childhood maltreatment exposures and depressive symptoms in late adulthood, and 2) the mediating effects of dysregulated physiological stress system function and perceived stress in midlife on the aforementioned associations.Methods: Data come from the Biomarker project (n = 1,053) of the Midlife Development in the United States study. Latent profile analysis was used to identify sub-groups with differing childhood maltreatment type and chronicity. We then test our mediation hypothesis using a product of coefficients method procedure.Results: Two vulnerable sub-groups were identified (Class 2: Emotional and physical maltreatment class, n = 52, and Class 3: Sexual abuse class, n = 79) along with a normative sub-group (Class 1: Normative class, n = 922) comprising of a majority of adults. Both vulnerable sub-groups had higher levels of perceived stress in late adulthood. Perceived stress mediated the association between both vulnerable sub-groups and depressive symptoms. Physiological stress dysregulation mediated the association only between the emotional and physical maltreatment class and depressive symptoms in late adulthood.Conclusion: Therapeutic approaches targeted at prevention of perceived stress for both vulnerable sub-groups identified in this study and those targeting physiological dysregulation in addition for the emotional and physical maltreatment class could be critical for depressive symptom recovery.

Polygenic Influences on Pubertal Timing and Tempo and Depressive Symptoms in Boys and Girls.

This study used polygenic scoring (PGS) to test whether puberty-related genes were correlated with depressive symptoms, and whether there were indirect effects through pubertal maturation. The sample included 8,795 adolescents from the Avon Longitudinal Study of Parents and Children (measures of puberty drawn ages 8-17 years; of depressive symptoms at age 16.5 years). The PGS (derived from a genome-wide meta-analysis of later age at menarche) predicted boys' and girls' later pubertal timing, boys' slower gonadal development, and girls' faster breast development. Earlier perceived breast development timing predicted more depressive symptoms in girls. Findings support shared genetic underpinnings for boys' and girls' puberty, contributing to multiple pubertal phenotypes with differences in how these genetic variants affect boys' and girls' development.

Lability in Parent- and Child-Based Sources of Parental Monitoring Is Differentially Associated with Adolescent Substance Use.

Parental knowledge about adolescents' whereabouts and activities remains one of the strongest predictors of reduced adolescent substance use. A recent study found that across middle childhood and adolescence, parental knowledge is characterized by fluctuations on a year-to-year basis, termed lability, even more-so than by linear trends, and that lability too is a predictor of adolescent substance use (Lippold et al., Dev. Psychol. 17, 274-283, 2016). The present study replicates Lippold et al. (Dev. Psychol. 17, 274-283, 2016) by quantifying developmental change and lability in parental knowledge across adolescence and examining associations with drinking, smoking, and other drug use later in adolescence, and extends the study by examining the sources of knowledge: child disclosure, parental solicitation, and parental control, separately. Using a community-based sample of 1023 youth in the Northeastern region of the USA, all three sources of knowledge were characterized by developmental change and lability. In general, higher levels and steeper developmental declines in knowledge were associated with substance use outcomes. Findings for child disclosure replicated the prior findings: increased lability of child disclosure predicted substance use. Unexpectedly, decreased lability of parental solicitation and control was associated with worse substance use outcomes. Findings suggest different mechanisms by which lability in child- and parent-driven cultivation of knowledge is associated with substance use. If replicated in studies that address causality, these mechanisms could be leveraged for prevention/intervention efforts. For example, increasing the consistency of child disclosure may help prevent substance use, but teaching parents to be more responsive to time-specific challenges with adolescents may be more effective than increasing the consistency of parents' knowledge-building parenting behaviors.

Developmental Pathways from Genetic, Prenatal, Parenting and Emotional/Behavioral Risk to Cortisol Reactivity and Adolescent Substance Use: A TRAILS Study.

Cortisol reactivity is a frequently studied biomarker of substance use, though infrequently examined in adolescence. However, past research provides evidence that multiple developmental influences, including genetics and both prenatal and postnatal environmental influences, contribute both to cortisol reactivity and adolescent substance use. The aim of this study was to assess the impact of these earlier developmental influences on cortisol reactivity to a social stress challenge and adolescent substance use (smoking, alcohol, and marijuana use frequency assessed at age 16 years), using data from the TRacking Adolescents' Individual Lives Survey (TRAILS; N= 2230 adolescents, 51% female). Developmental pathways included polygenic risk, prenatal stress, warm parenting (age 11), and internalizing and externalizing problems (intercepts and change from 11-16 years). Cortisol reactivity was associated with smoking but not alcohol or marijuana use. Externalizing problems were the stronger predictor of adolescent substance use, but internalizing problems also had an important role. Prenatal stress and middle childhood parenting operated via middle childhood externalizing problems, and parenting also operated via trajectories of growth of externalizing problems in predicting adolescent substance use outcomes. Further, there were protective effects of internalizing problems for alcohol and marijuana use in the context of a more comprehensive model. These developmental influences did not attenuate the association of cortisol reactivity and smoking. These findings suggest a need to understand the broader developmental context regarding the impact of internalizing pathways to substance use, and that it is unlikely that cortisol reactivity and smoking are associated solely because of common developmental influences.