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.

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.

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.

Early childhood child care and disruptive behavior problems during adolescence: a 17-year population-based propensity score study.

BACKGROUND: Child-care services during early childhood provide opportunities for social interactions that may facilitate children's learning of acceptable social behaviors. Furthermore, they may reduce exposure to family adversity for some children. The aim of this study was to determine whether intensity of exposure to child-care services prior to age 5 years has a beneficial effect on disruptive behavior problems during adolescence, and whether the effect is more pronounced for children from low socioeconomic families. METHODS: N = 1,588 participants from the Québec Longitudinal Study of Child Development were assessed 14 times from 5 months to 17 years. Intensity of child-care exposure was measured from 5 months to 5 years of age. Main outcomes were self-reported physical aggression and opposition from age 12 to 17 years. Family socioeconomic status (SES) was measured at 5 months. Factors explaining differences in child-care use were controlled using propensity score weights (PSW). RESULTS: Children exposed to moderate-intensity child-care services (part-time child-care services before 1½ years and full time afterward) reported lower levels of physical aggression (d = -.11, p = .056) and opposition (d = -.14, p = .029) during adolescence compared to children exposed to low-intensity child-care services. A significant child care by SES interaction (p = .017) for physical aggression indicated that the moderate-intensity child-care effect was specific to children from low SES families (d = -.36, p = .002). No interaction with socioeconomic status was found for opposition. CONCLUSIONS: Moderate-intensity child-care services from infancy to school entry may prevent disruptive behavior during adolescence, especially for disadvantaged children.

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.

A three-factor model of common early onset psychiatric disorders: temperament, adversity, and dopamine.

Commonly comorbid early onset psychiatric disorders might reflect the varying expression of overlapping risk factors. The mediating processes remain poorly understood, but three factors show some promise: adolescent externalizing traits, early life adversity, and midbrain dopamine autoreceptors. To investigate whether these features acquire greater predictive power when combined, a longitudinal study was conducted in youth who have been followed since birth. Cohort members were invited to participate based on externalizing scores between 11 to 16 years of age. At age 18 (age 18.5 ± 0.6 y.o.), 52 entry criteria meeting volunteers had a 90-min positron emission tomography scan with [18F]fallypride, completed the Childhood Trauma Questionnaire, and were assessed with the Structured Clinical Interview for DSM-5. The three-factor model identified those with a lifetime history of DSM-5 disorders with an overall accuracy of 90.4% (p = 2.4 × 10-5) and explained 91.5% of the area under the receiver operating characteristic curve [95% CI: .824, 1.000]. Targeting externalizing disorders specifically did not yield a more powerful model than targeting all disorders (p = 0.54). The model remained significant when including data from participants who developed their first disorders during a three-year follow-up period (p = 3.5 × 10-5). Together, these results raise the possibility that a combination of temperamental traits, childhood adversity, and poorly regulated dopamine transmission increases risk for diverse, commonly comorbid, early onset psychiatric problems, predicting this susceptibility prospectively.

Developmental pathways linking childhood temperament with antisocial behavior and substance use in adolescence: Explanatory mechanisms in the peer environment.

This study investigated 3 developmental pathways involving the peer environment that may explain how certain temperamental dispositions in childhood may become manifested in later antisocial behavior and substance use. A total of 411 (52% boys) Canadian children were followed annually from ages 6 to 15 years. The study tested whether the temperamental traits approach, negative reactivity and attention (assessed at ages 6-7 years), were associated with overt antisocial behavior, covert antisocial behavior and illicit substance use (assessed at ages 14-15 years), via poor social preference among peers, inflated social self-perception and antisocial behavior of peer-group affiliates (assessed throughout ages 8-13 years). Results indicated that negative reactivity was indirectly associated with overt antisocial behavior and substance use via poor social preference. Specifically, negative reactivity in earlier childhood predicted poor social preference in later childhood and early adolescence. This poor social standing among peers, in turn, predicted more engagement in overt antisocial behavior but less substance use in later adolescence. Over and above the influence of social preference, negative reactivity predicted engagement in all 3 outcomes via children's antisocial behavior in childhood and early adolescence. Inflated social self-perception and antisocial behavior of peer-group affiliates did not mediate the link between temperament and the outcomes under scrutiny. No sex differences in developmental pathways from temperament to the outcomes were found. To further our understanding of the developmental link between childhood temperament and later antisocial behavior and substance use, we need to recognize the role of peer environmental factors, specifically poor preference among peers. (PsycINFO Database Record