Concurrent and prospective associations between family socioeconomic status, social support and salivary diurnal and hair cortisol in adolescence.

BACKGROUND: Exposure to socioeconomic adversity is hypothesized to impact hypothalamic-pituitary-adrenal (HPA) axis activity and cortisol secretion, but existing evidence is inconsistent. Yet, few studies have investigated this association using a developmental approach that considers potential protective contextual factors. This study examined the role of stability and changes in family socioeconomic status (SES) in the prediction of multiple cortisol indicators and tested whether social support moderated these associations. METHODS: Participants were part of a population-based sample of twin pairs recruited at birth. Family SES was assessed in early childhood (ages 0-5) and mid-adolescence (age 14). Social support was assessed at ages 14 and 19. Diurnal cortisol (n = 569) was measured at age 14 at awakening, 30 min later, in the afternoon and evening over four non-consecutive days. Hair cortisol concentration (HCC, n = 704) was measured at age 19. All data were collected before the pandemic and multilevel regression models were conducted to account for the nested data structure. RESULTS: Youth exposed to lower family SES levels in childhood and mid-adolescence had a flatter diurnal slope and higher HCC compared with those who experienced upward socioeconomic mobility in mid-adolescence. Contrastingly, mid-adolescence SES showed no association with the diurnal slope or HCC for youth from higher-SES households in early childhood. Moreover, youth raised in higher-SES families in early childhood had a higher CAR in mid-adolescence if they reported greater social support in mid-adolescence. Social support also moderated the SES-cortisol association in mid-adolescence, with higher-SES youth showing higher awakening cortisol secretion when reporting more social support. CONCLUSIONS: Our findings support the hypothesis that early socioeconomic adversity sensitizes HPA axis activity to later socioeconomic disadvantage, which may bear consequences for socioemotional and behavioral functioning.

Genetic and phenotypic evidence of the predictive validity of preschool parent reports of hyperactivity/impulsivity and inattention.

To determine the validity of parent reports (PRs) of ADHD in preschoolers, we assessed hyperactivity/impulsivity (HI) and inattention (IN) in 1114 twins with PRs at 1.5, 2.5, 4, 5, 14, 15, and 17 years, and teacher-reports at 6, 7, 9, 10, and 12. We examined if preschool PRs (1) predict high HI/IN trajectories, and (2) capture genetic contributions to HI/IN into adolescence. Group-based trajectory analyses identified three 6-17 years trajectories for both HI and IN, including small groups with high HI (N = 88, 10.4%, 77% boys) and IN (N = 158, 17.3%, 75% boys). Controlling for sex, each unit of HI PRs starting at 1.5 years and at 4 years for IN, increased more than 2-fold the risk of belonging to the high trajectory, with incremental contributions (Odds Ratios = 2.5-4.5) at subsequent ages. Quantitative genetic analyses showed that genetic contributions underlying preschool PRs accounted for up to a quarter and a third of the heritability of later HI and IN, respectively. Genes underlying 1.5-year HI and 4-year IN contributed to 6 of 8 later HI and IN time-points and largely explained the corresponding phenotypic correlations. Results provide phenotypic and genetic evidence that preschool parent reports of HI and IN are valid means to predict developmental risk of ADHD.

Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.

The phenotypic associations and gene-environment underpinnings of socioeconomic status and diurnal cortisol secretion in adolescence.

While converging evidence suggests that both environmental and genetic factors underlie variations in diurnal cortisol, the extent to which these sources of influence vary according to socioeconomic status (SES) has seldom been investigated, particularly in adolescence. To investigate whether a distinct genetic and environmental contribution to youth's diurnal cortisol secretion emerges according to family SES and whether the timing of these experiences matters. Participants were 592 twin pairs, who mostly came from middle-income and intact families and for whom SES was measured in childhood and adolescence. Diurnal cortisol was assessed at age 14 at awakening, 30 min later, in the afternoon and evening over four nonconsecutive days. SES-cortisol phenotypic associations were specific to the adolescence period. Specifically, higher awakening cortisol levels were detected in wealthier backgrounds, whereas higher cortisol awakening response (CAR) and diurnal changes were present at both ends of the SES continuum. Moreover, smaller genetic contributions emerged for awakening cortisol in youth from poorer compared to wealthier backgrounds. The results suggest that the relative contribution of inherited factors to awakening cortisol secretion may be enhanced or suppressed depending on the socio-family context, which may help to decipher the mechanisms underlying later adjustment.

Links between peer victimization, dating violence victimization and depression in adolescence: A genetically-informed study.

OBJECTIVE: The current study aimed to test if individuals with inherent dispositions to depression-related cognitions and behaviors are more at risk of experiencing relational difficulties, such as peer victimization and dating violence victimization. METHOD: This study used a genetically informed design with 806 twins (51.5% girls) to test 1) if at least part of the association between peer victimization in school and dating violence victimization in emerging adulthood can be explained by common underlying heritable factors. Participants provided repeated assessments of their peer victimization in school at ages 13 through 17, their depression symptoms at ages 13 through 19, as well as their victimization in dating relationships at age 19. RESULTS: A Cholesky decomposition based on structural equation modeling supported the hypotheses. Specifically, the association between peer victimization and dating violence victimization was to a significant extent explained by common underlying genetic vulnerabilities that were associated with depression symptoms. No sex moderation was found. CONCLUSIONS: The findings highlight the importance of addressing early indicators of vulnerability toward depression symptoms to prevent victimization by peers or dating partners.

Link Between Peer Victimization in College and Cortisol Secretion: Roles of Genetic Vulnerabilities and Social Support.

It is unclear whether peer victimization in college interacts with genetic vulnerabilities or social support in predicting cortisol secretion. This issue was addressed using a sample of 162 Monozygotic and 237 Dizygotic twin pairs (54% females; 86% Whites, 6% Blacks, 6% Asians, 0.3% Native North Americans). At age 19, participants provided hair for cortisol extraction and reported about victimization in college and support by the mother, father, and best friend. Biometric modeling revealed that environmental influences on cortisol secretion were reduced and genetic influences exacerbated when victimization was high. Moderate to high maternal support mitigated the association between victimization and high cortisol secretion. The findings suggest that victimization in college contributes to physical "wear-and-tear", which may be counteracted by social support.

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts.

BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Unique and interactive associations of proactive and reactive aggression with cortisol secretion.

The association between aggressive behaviors and diurnal cortisol levels has been debated over the past two decades, as some studies found a negative link between the two, whereas others reported no or a positive association. One possible explanation for these contradictory results is that past studies failed to distinguish between proactive (PROA) and reactive (REA) aggression. The present study examined the unique and joint associations of PROA and REA with three diurnal cortisol indicators: awakening levels, awakening response, and diurnal change. Participants were 542 youths (55.4% girls) followed longitudinally. Teachers evaluated aggressive behaviors when participants were in Grades 4 and 6. In Grade 8, participants provided four saliva samples (i.e., awakening, 30 min thereafter, late afternoon, and bedtime) on four collection days. Controlling for several confounders, multilevel regression analyses revealed an inverse relation between PROA and the CAR in boys who displayed lower or moderate levels of REA, but not in those who exhibited higher levels of REA. No associations emerged with other cortisol indicators. These results are consistent with reports of lower physiological activity in individuals with PROA and underscore the confounding influence of REA in the association between the CAR and proactive aggression.

Maternal depressive symptoms and children's cognitive school readiness: the role of gene-environment interplay.

Maternal depressive symptoms are a robust risk factor for poor cognitive outcomes in children, yet the role of gene-environment interplay in this association is not well understood. The objective of this study was to evaluate gene-environment interaction in the association between maternal depressive symptoms and children's cognitive school readiness. Data come from a population-based birth cohort of 538 twin pairs. Maternal depressive symptoms were self-reported (Centre for Epidemiologic Studies Depression Scale) when children were aged 6 and 18 months (a mean score was used). Children's cognitive school readiness was assessed using the Lollipop Test when children were aged 5 years. Analyses were conducted with structural equation modeling. Maternal depressive symptoms were correlated with children's cognitive school readiness (r = -0.10). Shared environmental factors explained most of the variance in children's cognitive school readiness (52%). The remaining variance was accounted for by genetic (30%) and nonshared environmental factors (18%). As the level of maternal depressive symptoms increased, the relative contribution of nonshared environmental factors to the variance in children's cognitive school readiness increased (0.14 [95% CI: 0.04 to 0.24]), whereas the relative contribution of genetic factors decreased (-0.28 [-0.64 to 0.08]). In contexts of elevated maternal depressive symptoms, environmental - and potentially modifiable - factors may be especially important for shaping children's cognitive outcomes. This suggests that interventions to improve the early childhood environment of children exposed to maternal depressive symptoms may improve their cognitive outcomes.

Early temperamental and biological predictors of dimensions of social withdrawal in childhood.

Social wariness and preference for solitude, two dimensions of social withdrawal, show unique associations with various socioemotional difficulties in childhood, including internalizing and peer problems. However, their early childhood predictors remain vastly undocumented. The present study aimed to examine whether early indicators of reactivity in situations of unfamiliarity such as behavioral inhibition, affect, and cortisol independently, or in interaction with emotion regulation as indexed by vagal tone, predict later social wariness and preference for solitude. Participants were 1209 children from the Quebec Newborn Twin Study. Vagal tone was assessed at 5 months, and behavioral inhibition, affect, and cortisol were assessed at 19 months in situations of unfamiliarity. Mothers, teachers, and peers evaluated social wariness and preference for solitude repeatedly from 4 to 10 years old. Findings show that three temperamental dimensions, social inhibition, nonsocial inhibition, and affect accounted for the variability in reactions to unfamiliarity. Behavioral inhibition to social unfamiliarity at 19 months predicted social wariness during the preschool years. Poor vagal regulation at 5 months exacerbated the risk associated with negative affect at 19 months to predict preference for solitude during the preschool years. Overall, results show that social wariness and preference for solitude may follow different developmental pathways.

The Intensity of Formal Child-Care Attendance Decreases the Shared Environment Contribution to School Readiness: A Twin Study.

The purpose of this study was to explore if child-care intensity (hours/weeks) and age of onset could moderate genetic and environmental contributions to school readiness. A sample of 648 (85% Whites; 50% Females) pairs of twins was used to compute a GxE, CxE and ExE interaction analyses. The moderation model showed that shared environment explains 48% of individual differences in school readiness for children not attending formal child-care, and decreased gradually to a mere 3% for children attending formal child-care full time, e.g., 40 h per week. Age of onset exerted no moderation effect. The results support the hypothesis that child-care acts as a normalizing environment, possibly buffering negative effects from low-quality home environments on school readiness.

Classroom Placement and Twins' Social Behaviors in Elementary School: Providing Empirical Evidence to Inform Educational Policy.

Classroom placement of twins is an ongoing issue for educational policy. Many educational jurisdictions have standard policy most commonly founded in the belief that separation supports individual identity, personal development and academic opportunity. This study examined the effects of classroom placement in a sample of 560 twin pairs whose behaviors were assessed from ages 5 to 12 years. We found no detrimental effect of classroom sharing on twins' social development. In contrast, this study provides evidence that educating twins together is associated with modest positive twins' behaviors and social functioning at school. Implications for educational policies are further discussed.

Maternal Parenting Behaviors Amplify Environmental Influences on Developmental Trajectories of Alcohol Use During Adolescence.

Compared to peer alcohol use, less is known on how parenting practices may modify genetic and environmental contributions to alcohol use longitudinally across adolescence. This study examined whether two maternal parenting behaviors, supervision and harsh parenting, may suppress or amplify genetic and environmental influences on three distinct developmental trajectories of adolescent alcohol use: normative increasing, early-onset, and low trajectories. Participants were drawn from a longitudinal study of a population-based twin sample (N = 842, 84% European descent, 52.7% female). Adolescents self-reported their past year alcohol use at ages 13, 14, 15, and 17 years, and their mothers reported their supervision and harsh parenting when twins were 13, 15, and 17 years old. Maternal supervision amplified non-shared environmental influence on the normative increasing and early-onset trajectories, whereas maternal harsh parenting amplified shared environmental influence on the early-onset trajectory and non-shared environmental influence on the low trajectory, respectively. The findings suggest maternal parenting practices as a potent developmental context that modulates the environmental influences of other proximal processes on adolescent alcohol use, and suggest that family-based parenting-focused intervention could be especially beneficial for adolescents following the early-onset trajectory.

Polygenic scores differentially predict developmental trajectories of subtypes of social withdrawal in childhood.

BACKGROUND: Children who consistently withdraw from social situations face increased risk for later socioemotional difficulties. Twin studies indicate that genetic factors substantially account for the persistence of social withdrawal over time. However, the molecular genetic etiology of chronic courses of social wariness and preference for solitude, two dimensions of social withdrawal, remains undocumented. The objectives of the present study were (a) to identify high-risk trajectories for social wariness and preference for solitude in childhood and (b) to examine whether falling on these high-risk trajectories can be predicted by specific polygenic scores for mental health traits and disorders and by a general polygenic predisposition to these traits. METHODS: Teachers evaluated 971 genotyped children at five occasions (age 6 to 12 years) from two prospective longitudinal studies, the Quebec Newborn Twin Study and the Quebec Longitudinal Study of Child Development. Developmental trajectories for social wariness and preference for solitude were identified. We tested whether polygenic scores for attention deficit hyperactivity disorder, autism spectrum disorder, depression, loneliness, and subjective well-being, as well as a general mental health genetic risk score derived across these traits, were associated with the developmental trajectories. RESULTS: Polygenic scores differentially predicted social wariness and preference for solitude. Only the loneliness polygenic score significantly predicted the high trajectory for social wariness. By contrast, the general mental health genetic risk score factor was associated with the trajectory depicting high-chronic preference for solitude. CONCLUSIONS: Distinct associations were uncovered between the polygenic scores, social wariness, and preference for solitude.

Victimization by Friends and Victimization by Other Peers: Common Risk Factors or Mutual Influence?

Much research effort has been placed on understanding peer victimization. However, few studies have focused on victimization within friendships, which affects up to half of adolescents and bears similar consequences as victimization by the larger peer group. This study examined the temporal stability and the risk factors of victimization within friendships and victimization by other peers. In regard to the first objective, moderate to high levels of stability over a one-year period were expected for victimization by friends and by other peers. In regard to the second objective, two - not necessarily mutual exclusive - hypotheses were tested. The Common Risk Factors Hypothesis postulated that victimization by friends and by other peers share common personal and familial risk factors. Alternatively, the Mutual Influence Hypothesis proposed that victimization within one relationship context may increase the risk of being victimized in the other relationship context. These hypotheses were tested with a sample of 878 adolescents (Mage = 15.08 years, range 14.50-15.75; 52% female) assessed in Grades 8 and 9. Structural equation modeling revealed moderate and weak one-year stability for victimization by friends and by other peers, respectively. No common risk factors emerged, but victimization within one relationship context increased the risk of victimization in the other relationship context one year later. These results are in line with the mutual influence hypothesis and provide evidence of a cross-context transfer of victimization in adolescence.

Birth weight is associated with adolescent brain development: A multimodal imaging study in monozygotic twins.

Previous research has shown that the prenatal environment, commonly indexed by birth weight (BW), is a predictor of morphological brain development. We previously showed in monozygotic (MZ) twins associations between BW and brain morphology that were independent of genetics. In the present study, we employed a longitudinal MZ twin design to investigate whether variations in prenatal environment (as indexed by discordance in BW) are associated with resting-state functional connectivity (rs-FC) and with structural connectivity. We focused on the limbic and default mode networks (DMNs), which are key regions for emotion regulation and internally generated thoughts, respectively. One hundred and six healthy adolescent MZ twins (53 pairs; 42% male pairs) followed longitudinally from birth underwent a magnetic resonance imaging session at age 15. Graph theoretical analysis was applied to rs-FC measures. TrackVis was used to determine track count as an indicator of structural connectivity strength. Lower BW twins had less efficient limbic network connectivity as compared to their higher BW co-twin, driven by differences in the efficiency of the right hippocampus and right amygdala. Lower BW male twins had fewer tracks connecting the right hippocampus and right amygdala as compared to their higher BW male co-twin. There were no associations between BW and the DMN. These findings highlight the possible role of unique prenatal environmental influences in the later development of efficient spontaneous limbic network connections within healthy individuals, irrespective of DNA sequence or shared environment.

A Genetic Cross-Lagged Study of the Longitudinal Association Between Anxiety and Depressive Symptoms During Childhood.

This study documented the etiology contributions between anxiety symptoms (AS) and depressive symptoms (DS) from ages 6-12 years. Teachers assessed AS and DS in 1112 twins at 5 time points. A genetic cross-lagged model was used to estimate genetic/environmental contributions to cross-sectional, cross-age and cross-lag associations. The variance in AS and DS was largely time-specific and more genetic in nature for DS than for AS. Previous DS predicted subsequent DS better than cross-lag or previous common effects, and AS up to age 9 better than previous AS or previous common effects. Thereafter, previous AS predicted subsequent AS. All predictions involved both genetic and unique environment. Suppression effects were found and, when controlled, AS marginally predicted DS from age 7 onward through genetic influences. AS and DS are associated throughout childhood. DS are more stable than AS, and more central to both subsequent AS and DS. AS marginally contribute to subsequent DS.

Contribution of genes and environment to the longitudinal association between childhood impulsive-aggression and suicidality in adolescence.

BACKGROUND: Population-based and family studies showed that impulsive-aggression predicts suicidality; however, the underlying etiological nature of this association is poorly understood. The objective was to determine the contribution of genes and environment to the association between childhood impulsive-aggression and serious suicidal ideation/attempt in young adulthood. METHODS: N = 862 twins (435 families) from the Quebec Newborn Twin Study were followed up from birth to 20 years. Repeated measures of teacher-assessed impulsive-aggression were modeled using a genetically informed latent growth model including intercept and slope parameters reflecting individual differences in the baseline level (age 6 years) and in the change (increase/decrease) of impulsive-aggression during childhood (6 to 12 years), respectively. Lifetime suicidality (serious suicidal ideation/attempt) was self-reported at 20 years. Associations of impulsive-aggression intercept and slope with suicidality were decomposed into additive genetic (A) and unique environmental (E) components. RESULTS: Additive genetic factors accounted for an important part of individual differences in impulsive-aggression intercept (A = 90%, E = 10%) and slope (A = 65%, E = 35%). Genetic (50%) and unique environmental (50%) factors equally contributed to suicidality. We found that 38% of the genetic factors accounting for suicidality were shared with those underlying impulsive-aggression slope, whereas 40% of the environmental factors accounting for suicidality were shared with those associated with impulsive-aggression intercept. The genetic correlation between impulsive-aggression slope and suicidality was 0.60, p = .027. CONCLUSIONS: Genetic and unique environmental factors underlying suicidality significantly overlap with those underlying childhood impulsive-aggression. Future studies should identify putative genetic and environmental factors to inform prevention.

Trajectories of pain and anxiety in a longitudinal cohort of adolescent twins.

BACKGROUND: Adolescence is critical to intercept chronic/persistent pain and decipher its association with anxiety. We ascertained adolescent pain trajectories, their demographic and clinical correlates, the longitudinal association with opiate prescriptions at age 19, and the etiology of the covariation between adolescent pain problems and anxiety symptoms. METHODS: Longitudinal assessment of: 6 common pain problems at age 12, 13, 14, 15, and 17 years; 7 common anxiety symptoms at age 12, 13, and 14 years; opiates' prescriptions at age 19, in the Quebec Newborn Twin Study birth cohort of 667 twin pairs born between 1995-1998. RESULTS: Analyses yielded three trajectories of: "none-to-minimal" (34.3%), "sporadic" (56.7%), and "frequent" (9.0%) pain problems between age 12-17. Anxiety (odds ratios [OR] ORage12 : 2.38; confidence interval [CI]: 1.26-4.47; ORage13 : 3.96; CI: 1.73-9.05; ORage14 : 5.45; CI: 2.67-11.11), the female sex (OR: 3.69; CI: 2.20-6.21), and lower socioeconomic status (OR: 0.87; CI: 0.77-0.98) were associated with the "frequent" compared to the "none-to-minimal" pain trajectory. Only the "frequent" pain trajectory predicted opioid prescriptions at age 19 (OR: 4.14; CI: 1.16-14.55). A twin bivariate latent growth curve model and a cross-lagged model showed that genetic factors and non-shared environmental factors common to both phenotypes influence the longitudinal association between anxiety and adolescent pain problems. CONCLUSIONS: The relatively common, adolescent "frequent pain" trajectory predicts early opioid prescriptions, and anxiety and adolescent pain share multiple etiological components. These data can inform diagnostic reasoning, clinical practice, and help reducing opioid prescriptions and abuse.

The bidirectional association between maternal speech and child characteristics.

Our aim was to assess whether infants influence the quantity and quality of their mothers' speech to them and, in turn, whether this maternal speech influences children's later language. As 189 mothers interacted with each of their twins at age 0;5, we calculated the number of utterances, the proportion of sensitive utterances, and the proportion of self-repeated utterances they produced. We later assessed the twins' language comprehension and production when they were 1;6, 2;6, and 5;2. Quantity of maternal speech predicted child language at 5;2, whereas sensitivity predicted child language at 2;6 and 5;2 and partial self-repetition predicted child language at 1;6. Conversely, sensitivity and partial self-repetition in maternal speech at 0;5 were associated with genetic factors from the child, indicating that infant characteristics influence the quality of maternal speech. Overall, our findings stress the importance of considering both directions in the association between maternal speech and child characteristics.