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.

Continuity and change of genetic and environmental influences on reading and reading-related neurocognitive skills: A systematic review of longitudinal twin studies.

Learning to read is a dynamic and cumulative process beginning from birth and continuing through the school years. Empirical data showed a decrease of additive genetic (A) and shared environmental (C) components and an increase of non-shared environmental (E) components from preschool to middle school. However, our understanding of the aetiology of continuity and change of reading skills across this developmental period is limited. Following the PRISMA guidelines, we reviewed the results of behavioral genetic research on reading-related neurocognitive skills of 13 longitudinal twin and adoptive sibling studies spanning from preschool/kindergarten to middle/high school. Our findings suggested that continuity was mainly explained by A components throughout the study periods, and, although to a lesser extent and less consistently, by C components during the early years; change was explained by new E components throughout the years, and also by new A components in the early years. As we are interested in models relevant to traits with early onset during development, it is crucial to deepen the investigation of how developmental time can moderate the genetic and environmental variation.

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.

Adolescent anxiety and pain problems: A joint, genome-wide investigation and pathway-based analysis.

Both common pain and anxiety problems are widespread, debilitating and often begin in childhood-adolescence. Twin studies indicate that this co-occurrence is likely due to shared elements of risk, rather than reciprocal causation. A joint genome-wide investigation and pathway/network-based analysis of adolescent anxiety and pain problems can identify genetic pathways that subserve shared etiopathogenetic mechanisms. Pathway-based analyses were performed in the independent samples of: The Quebec Newborn Twin Study (QNTS; 246 twin pairs and 321 parents), the Longitudinal Study of Child Development in Quebec (QLSCD; n = 754), and in the combined QNTS and QLSCD sample. Multiple suggestive associations (p<1×10-5), and several enriched pathways were found after FDR correction for both phenotypes in the QNTS; many nominally-significant enriched pathways overlapped between pain problems and anxiety symptoms (uncorrected p<0.05) and yielded results consistent with previous studies of pain or anxiety. The QLSCD and the combined QNTS and QLSCD sample yielded similar findings. We replicated an association between the pathway involved in the regulation of myotube differentiation (GO:0010830) and both pain and anxiety problems in the QLSDC and the combined QNTS and QLSCD sample. Although limited by sample size and thus power, these data provide an initial support to conjoint molecular investigations of adolescent pain and anxiety problems. Understanding the etiology underlying pain and anxiety co-occurrence in this age range is relevant to address the nature of comorbidity and its developmental pathways, and shape intervention. The replication across samples implies that these effects are reliable and possess external validity.

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.

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.

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.

Teachers' behaviour and children's academic achievement: Evidence of gene-environment interactions.

BACKGROUND: Children's academic achievement is considerably influenced by genetic factors, which rarely operate independently of environmental influences such as teachers' behaviour. Praise and punitive discipline are commonly used management strategies by teachers. However, their effects on the genetic expression of children's academic achievement are still unclear. AIMS: This study examined potential gene-environment interactions in the associations between children's estimated genetic disposition for academic achievement and teachers' use of praise and punitive discipline in predicting academic achievement. SAMPLE: The participants were 165 twin pairs in sixth grade (M = 12.1 years). METHODS: Teachers reported on children's academic achievement, as well as on their own behaviour. RESULTS: Multilevel regression analyses showed significant interactions between children's estimated genetic disposition for academic achievement and teachers' use of praise and punitive discipline, respectively, in predicting academic achievement. These interactions indicated an enhancement process, suggesting that genetically advantaged children are those most likely to benefit from regular praise and infrequent punishments from their teacher. Moreover, genetically advantaged children were not more (nor less) likely to receive praise or punishments than other students. However, students from underprivileged backgrounds were less likely to receive praise from their teachers. CONCLUSIONS: The results emphasize the importance of teachers' regular use of praise and infrequent punitive discipline to help genetically advantaged children reach their full potential. Future studies should investigate other protective factors of the school environment that might reduce the role of genetic influences that undermine disadvantaged youth's academic achievement.

Gene-Environment Interplay Linking Peer Victimization With Adolescents' Trajectories of Depressive Symptoms.

OBJECTIVE: This study examined to what extent genetic and environmental factors explain-either additively or interactively with peer victimization-different trajectories of adolescents' depressive symptoms and whether genetic factors related to distinct trajectories are correlated with peer victimization. METHOD: Participants included 902 twins (52% girls) who self-reported peer victimization and depressive symptoms in grades 6, 7, 8, 9, and 11. RESULTS: Growth mixture modeling revealed 3 trajectories of depressive symptoms: low (69.2% of participants), increasing (19.5%), and high-decreasing-increasing (11.3%). Biometric modeling showed that, for both sexes, genetic factors explained roughly half (52.6%, 47.5%) of the probability of following either a low or an increasing trajectory. Genetic influences (41%) were also observed for the high-decreasing-increasing trajectory, albeit only for girls. Nonshared environmental influences explained the remaining variances, along with shared environmental influences (27%) on the high-decreasing-increasing trajectory. Only for the low and the increasing trajectories, nonshared environmental influences increased with more frequent peer victimization (blow = 0.206, 95% CI [0.094, 0.325]; bincreasing = 0.246, 95% CI [0.143, 0.356]). Moreover, peer victimization was associated with a lower probability of a low trajectory and a higher probability of an increasing or high-decreasing-increasing trajectory, and these associations were mostly explained by common underlying genetic factors. CONCLUSION: Youth expressing (partly inherited) depressive symptoms may be at risk of peer victimization. However, increasing depressive symptoms in victims may be mitigated by other environmental factors except for those who enter adolescence with already high levels of depressive symptoms.

Child Cognitive Flexibility and Maternal Control: A First Step toward Untangling Genetic and Environmental Contributions.

Executive functions (EF) play an essential role in many spheres of child development. Therefore, it is crucial to get a better understanding of their etiology. Using a genetic design that involved 934 twins (400 monozygotic), this study examined the etiology of cognitive flexibility, a component of EF, at 5 years of age and its phenotypic and etiological associations with maternal control. Cognitive flexibility was measured in a laboratory setting at 5 years of age using a well-known EF-task, i.e. the Dimensional Change Card Sort (DCCS). Maternal control was measured using a self-report questionnaire. The univariate genetic model demonstrated that environmental factors mainly explained individual differences in preschoolers' performance on the DCCS task. A bivariate genetic model demonstrated that non-shared environmental mechanisms mainly explained the association (r = .-13) between maternal control and children's performance on the DCCS task. This study represents a preliminary step toward a better understanding of the genetic and environmental contributions underlying the relation between parenting behaviors and children's EF.

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.

A sequential model of the contribution of preschool fluid and crystallized cognitive abilities to later school achievement.

The present study documented in two distinct population-based samples the contribution of preschool fluid and crystallized cognitive abilities to school achievement in primary school and examined the mediating role of crystallized abilities in this sequence of predictive associations. In both samples, participants were assessed on the same cognitive abilities at 63 months (sample 1, n = 1072), and at 41 and 73 months (sample 2, n = 1583), and then with respect to their school achievement from grade 1 (7 years) to grade 6 (12 years). Preschool crystallized abilities were found to play a key role in predicting school achievement. They contributed substantially to school achievement in the early school years, but more modestly in the later years, due to the strong auto-regression of school achievement. They also mediated the association between fluid abilities and later school achievement in the early grades of school, with the former having modest direct contribution to the latter in the later grades. These findings are discussed regarding their implication for preventive interventions.

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.

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.

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.

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.

Association between the timing of family socioeconomic deprivation and adolescence hair cortisol among adolescent twins: A study of the genetic and environmental processes involved.

BACKGROUND: While evidence shows that lower socioeconomic status (SES) is related to dysregulated hair cortisol concentration (HCC), the genetic and environmental processes underlying this association remain understudied. OBJECTIVES: (1) to examine whether childhood and adolescence SES are phenotypically related to late adolescence HCC and to what extent these associations are explained by common underlying genetic factors (2) to estimate whether the genetic and environmental etiology of HCC varies according to SES and the timing of these experiences. METHODS: Participants were 422 twin pairs for whom SES was measured in childhood (ages 0-5 years) and adolescence (age 14 years). Hair cortisol was assessed at age 19. RESULTS: Additive genetic factors explained 39% of variability in HCC, whereas nonshared environmental factors accounted for the remaining 61%. A significant negative association emerged between HCC and family SES assessed in adolescence (ß=-.11,p = .02), which was entirely explained by common underlying environmental influences. We also found evidence of stronger genetic contributions to HCC among youths who lived in more disadvantaged households during childhood in comparison to those from wealthier backgrounds. CONCLUSIONS: This study provides first-time evidence that the association between adolescence SES and HCC is environmentally-explained and that genetic influences underlying HCC are not uniformly distributed across the family SES continuum measured during childhood. These findings may pave the way for a fuller understanding of the impact of early adversity on HPA axis activity.

The gene environment aetiology of freezing and its relationship with internalizing symptoms during adolescence.

BACKGROUND: The freezing response is a universal response to threat, linked to attentive immobility and action preparation. It is relevant for acute stress coping in animals and humans, and subtle deviations in toddler freezing duration (absence of, or excessively long reactions) have been linked to higher risk for internalizing symptoms in adolescence. Yet, while individual freezing tendencies are relatively stable throughout life, little is known about their gene-environment aetiology. METHODS: We investigated the heritability of toddler freezing in the Quebec Newborn Twin Study (QNTS; n=508 twins) by fitting behavioural genetic models to video-coded freezing responses during a robot confrontation. Furthermore, we examined the predictive associations between toddler freezing and internalizing symptoms (anxiety and depressive symptoms), as they unfold during adolescence (ages 12-19 years) using linear mixed-effects models. FINDINGS: Freezing was found to be moderately heritable (45% of the variance accounted for by genetic factors). The remaining variance was explained by unique environmental factors, including measurement error. No significant contribution of shared environmental factors was noted. Additionally, shorter freezing was associated with more internalizing symptoms in adolescence at trend level, a pattern that was significant for depressive but not anxiety symptoms. INTERPRETATION: Freezing is an adaptive coping mechanism in early childhood, which is partly driven by genetic factors. Crucially, the absence or shorter duration of these behaviours may signal vulnerability to depressive problems later in life. FUNDING: Canadian Institutes of Health Research and Research Fund of Quebec-Health and Society and Culture. Consolidator grant from the European Research Council (ERC_CoG-2017_772337).

From preschool language skills to writing in adolescence: Evidence of genetic continuity.

Given the importance of writing for academic achievement, this study aimed to understand how early oral language contributes to later writing skills. The first objective was to determine if preschool language skills were associated with high school writing, and if so, whether they contributed directly or indirectly through school age language. The second aim was to explore the extent to which genetic and environmental factors explained these potential associations. The sample was drawn from the Quebec Newborn Twin Study, a longitudinal follow-up of twins born in the greater Montreal area, Quebec, Canada. Language skills were assessed when children were 1.5, 2.5, 6, 7, 10, and 12 years old. Writing skills were measured at 15 years old. Participants who completed the writing task in French were included in the study (n = 316 twin pairs: 46% males). Mothers of these participants self-identified mostly as White. About 74% of them had a postsecondary diploma or certificate, and 27% further had a university degree. Most families had an income higher than 30,000 CND. Results indicate that preschool language was modestly associated with high school writing (r = .25) and that school age language fully mediated this association. Genes explained 53% of the association between preschool language and school age language and 64% of the association between school age language and high school writing. These results highlight the developmental continuity from oral to written language from preschool to high school and show that genetic factors largely account for this continuity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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.