Polygenic risk and hostile environments: Links to stable and dynamic antisocial behaviors across adolescence.

Adverse environments are linked to elevated youth antisocial behavior. However, this relation is thought to depend, in part, on genetic susceptibility. The present study investigated whether polygenic risk for antisociality moderates relations between hostile environments and stable as well as dynamic antisocial behaviors across adolescence. We derived two antisocial-linked polygenic risk scores (PRS) (N = 721) based on previous genome-wide association studies. Forms of antisocial behavior (nonaggressive conduct problems, physical aggression, social aggression) and environmental hostility (harsh parenting and school violence) were assessed at age 13, 15, and 17 years. Relations to individual differences stable across adolescence (latent stability) vs. time-specific states (timepoint residual variance) of antisocial behavior were assessed via structural equation models. Higher antisocial PRS, harsh parenting, and school violence were linked to stable elevations in antisocial behaviors across adolescence. We identified a consistent polygenic-environment interaction suggestive of differential susceptibility in late adolescence. At age 17, harsher parenting was linked to higher social aggression in those with higher antisocial PRS, and lower social aggression in those with lower antisocial PRS. This suggests that genetics and environmental hostility relate to stable youth antisocial behaviors, and that genetic susceptibility moderates home environment-antisocial associations specifically in late adolescence.

Associations among oxytocin receptor gene (OXTR) DNA methylation in adulthood, exposure to early life adversity, and childhood trajectories of anxiousness.

Recent models propose deoxyribonucleic acid methylation of key neuro-regulatory genes as a molecular mechanism underlying the increased risk of mental disorder associated with early life adversity (ELA). The goal of this study was to examine the association of ELA with oxytocin receptor gene (OXTR) methylation among young adults. Drawing from a 21-year longitudinal cohort, we compared adulthood OXTR methylation frequency of 46 adults (23 males and 23 females) selected for high or low ELA exposure based on childhood socioeconomic status and exposure to physical and sexual abuse during childhood and adolescence. Associations between OXTR methylation and teacher-rated childhood trajectories of anxiousness were also assessed. ELA exposure was associated with one significant CpG site in the first intron among females, but not among males. Similarly, childhood trajectories of anxiousness were related to one significant CpG site within the promoter region among females, but not among males. This study suggests that females might be more sensitive to the impact of ELA on OXTR methylation than males.

Severe congenital malformations, family functioning and parents' separation/divorce: a longitudinal study.

BACKGROUND: We aim to explore the association of a severe congenital malformation (SCM) with postnatal family functioning and parents' separation/divorce and to examine if this association might be moderated by birth order of the child and parental level of education. SCM refers to malformations that, without medical intervention, cause handicap or death. METHODS: Using the Quebec Longitudinal Study of Child Development, an ongoing population-based birth cohort study initiated in 1998, we compared 1675 families of children with and without a SCM to identify if having a child with a SCM was associated with maternal perception of family functioning. We examined if an SCM was associated with parents' separation and examined parents' education level and birth order of the children to evaluate whether these factors had any moderating effect on the results. RESULTS: There were no significant differences in family functioning between families with and without a SCM child at 5 and 17 months. At 5 months, family functioning was significantly better (P = 0.03) for families with a SCM firstborn child than for families with a SCM child that is not firstborn. For parental separation, no significant differences were observed at 5 and 29 months and 4 years. No significant moderating effects were observed for birth order and parental education on parental separation. CONCLUSIONS: Families of children with a SCM do not appear to be at higher risk of family dysfunction within the first 17 months after birth nor of parental separation within the first 4 years after birth. Family functioning tends to be worst in families where the child with SCM is the second or subsequent child born.

Monoamine oxidase A gene promoter methylation and transcriptional downregulation in an offender population with antisocial personality disorder.

BACKGROUND: Antisocial personality disorder (ASPD) is characterised by elevated impulsive aggression and increased risk for criminal behaviour and incarceration. Deficient activity of the monoamine oxidase A (MAOA) gene is suggested to contribute to serotonergic system dysregulation strongly associated with impulsive aggression and antisocial criminality. AIMS: To elucidate the role of epigenetic processes in altered MAOA expression and serotonin regulation in a population of incarcerated offenders with ASPD compared with a healthy non-incarcerated control population. METHOD: Participants were 86 incarcerated participants with ASPD and 73 healthy controls. MAOA promoter methylation was compared between case and control groups. We explored the functional impact of MAOA promoter methylation on gene expression in vitro and blood 5-HT levels in a subset of the case group. RESULTS: Results suggest that MAOA promoter hypermethylation is associated with ASPD and may contribute to downregulation of MAOA gene expression, as indicated by functional assays in vitro, and regression analysis with whole-blood serotonin levels in offenders with ASPD. CONCLUSIONS: These results are consistent with prior literature suggesting MAOA and serotonergic dysregulation in antisocial populations. Our results offer the first evidence suggesting epigenetic mechanisms may contribute to MAOA dysregulation in antisocial offenders.

A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome.

BACKGROUND: Physical aggression (PA) tends to have its onset in infancy and to increase rapidly in frequency. Very little is known about the genetic and environmental etiology of PA development during early childhood. We investigated the temporal pattern of genetic and environmental etiology of PA during this crucial developmental period. METHOD: Participants were 667 twin pairs, including 254 monozygotic and 413 dizygotic pairs, from the ongoing longitudinal Quebec Newborn Twin Study. Maternal reports of PA were obtained from three waves of data at 20, 32 and 50 months. These reports were analysed using a biometric Cholesky decomposition and linear latent growth curve model. RESULTS: The best-fitting Cholesky model revealed developmentally dynamic effects, mostly genetic attenuation and innovation. The contribution of genetic factors at 20 months substantially decreased over time, while new genetic effects appeared later on. The linear latent growth curve model revealed a significant moderate increase in PA from 20 to 50 months. Two separate sets of uncorrelated genetic factors accounted for the variation in initial level and growth rate. Non-shared and shared environments had no effect on the stability, initial status and growth rate in PA. CONCLUSIONS: Genetic factors underlie PA frequency and stability during early childhood; they are also responsible for initial status and growth rate in PA. The contribution of shared environment is modest, and perhaps limited, as it appears only at 50 months. Future research should investigate the complex nature of these dynamic genetic factors through genetic-environment correlation (r GE) and interaction (G×E) analyses.

Childhood trajectories of inattention, hyperactivity and oppositional behaviors and prediction of substance abuse/dependence: a 15-year longitudinal population-based study.

Numerous prospective studies have shown that children diagnosed with attention deficit/hyperactivity disorder (ADHD) are at higher risk of long-term substance abuse/dependence. However, there are three important limits to these studies: (a) most did not differentiate the role of hyperactivity and inattention; (b) most did not control for associated behavioral problems; and (c) most did not consider females. Our aim was to clarify the unique and interactive contributions of childhood inattention and hyperactivity symptoms to early adulthood substance abuse/dependence. Behavioral problems of 1803 participants (814 males) in a population-based longitudinal study were assessed yearly between 6 and 12 years by mothers and teachers. The prevalence of substance abuse/dependence at age 21 years was 30.7% for nicotine, 13.4% for alcohol, 9.1% for cannabis and 2.0% for cocaine. The significant predictors of nicotine dependence were inattention (odds ratio (OR): 2.25; 95% confidence interval (CI): 1.63-3.11) and opposition (OR: 1.65; 95%: 1.20-2.28). Only opposition contributed to the prediction of cannabis dependence (OR: 2.33; 95% CI: 1.40-3.87) and cocaine dependence (OR: 2.97; 95% CI: 1.06-8.57). The best behavioral predictor of alcohol abuse/dependence (opposition) was only marginally significant (OR: 1.38; 95% CI: 0.98-1.95). Frequent oppositional behaviors during elementary school were clearly the most pervasive predictors of substance abuse/dependence in early adulthood. The association of childhood ADHD with substance abuse/dependence is largely attributable to its association with opposition problems during childhood. However, inattention remained an important predictor of nicotine dependence, in line with genetic and molecular commonalities between the two phenotypes suggested in the literature.

KmL3D: a non-parametric algorithm for clustering joint trajectories.

In cohort studies, variables are measured repeatedly and can be considered as trajectories. A classic way to work with trajectories is to cluster them in order to detect the existence of homogeneous patterns of evolution. Since cohort studies usually measure a large number of variables, it might be interesting to study the joint evolution of several variables (also called joint-variable trajectories). To date, the only way to cluster joint-trajectories is to cluster each trajectory independently, then to cross the partitions obtained. This approach is unsatisfactory because it does not take into account a possible co-evolution of variable-trajectories. KmL3D is an R package that implements a version of k-means dedicated to clustering joint-trajectories. It provides facilities for the management of missing values, offers several quality criteria and its graphic interface helps the user to select the best partition. KmL3D can work with any number of joint-variable trajectories. In the restricted case of two joint trajectories, it proposes 3D tools to visualize the partitioning and then export 3D dynamic rotating-graphs to PDF format.

Childhood trajectories of anxiousness and disruptiveness explain the association between early-life adversity and attempted suicide.

BACKGROUND: Suicidal behavior is frequently associated with a history of childhood abuse yet it remains unclear precisely how early life adversity may increase suicide risk later in life. As such, our aim was to examine whether lifetime trajectories of disruptiveness and anxiousness trait dysregulation explain the association between childhood adversity and suicidal behavior; and moreover, to test the potential modifying effects of mental disorders on these associations. METHOD: A sample of 1776 individuals from a prospective school-based cohort followed longitudinally for over 22 years was investigated. We tested the influence of disruptiveness and anxiousness trajectories from age 6 to 12 years on the association between childhood adversity (i.e. sexual and physical abuse) and history of suicide attempts (SA) using logistic regression models. Both adolescent externalizing and internalizing Axis I disorders and gender were tested as potential modifiers of these associations. RESULTS: Four distinct longitudinal trajectories were identified for both disruptiveness and anxiousness. The high disruptiveness trajectory accounted for the association between childhood adversity and SA, but only for females. The high anxiousness trajectory also explained the association between adversity and SA; however, in this case it was not sex but mental disorders that influenced the potency of the mediating effect. More specifically, anxiousness fully explained the effect of adversity on SA in the presence of externalizing disorders, whereas in the absence of these disorders, this effect was significantly attenuated. CONCLUSIONS: This study provides evidence that both disruptiveness and anxiousness play an important role in explaining the relationship between childhood adversity and SA.

Multivariate dependencies between difficult childhood, temperament and antisocial personality disorder in a population of French male prisoners.

BACKGROUND: The aim of this study was to contribute to clarification of the relations between antisocial personality disorder (APD) and its potential risk factors in a population of 560 French male prisoners. METHODS: Adverse childhood was assessed as a latent variable determined by several traumatic events. APD (MINI), character and temperament (Cloninger's model), WAIS®-III similarities subtest and psychosocial characteristics were assessed by two clinicians. The WAIS®-III subtest accounts for verbal and cognitive performance. We used a structural model to determine the weight of the different pathways between adverse childhood and APD. RESULTS: Study confirmed the major and direct role of adverse childhood (standardized coefficient=0.48). An intermediate effect mediated by character (considered as a global variable) and novelty-seeking was also shown, confirming previous results from the literature. CONCLUSION: This study emphasizes the role of adverse childhood in APD, suggesting the potential benefit of early intervention in the prevention of antisocial behaviours.

Preventing disruptive boys from becoming heavy substance users during adolescence: a longitudinal study of familial and peer-related protective factors.

Childhood disruptiveness is one of the most important antecedents of heavy substance use in adolescence, especially among boys. The first aim of the present study is to verify whether parental monitoring and friend conventionality protect disruptive boys from engaging in heavy substance-use in adolescence. The second purpose is to examine whether these protective effects are strengthened by attachment to parents or friends respectively. Finally, the third objective is to verify whether the expected protective effect of parental monitoring could be mediated through exposure to conventional friends. A sample of 1037 boys from low socioeconomic neighbourhoods was followed from childhood (age 6) to adolescence (age 15). Parent, teacher, and self-reported measures were used to measure disruptiveness, parental monitoring, family attachment, friend conventionality, and attachment to friends. Results suggest that parental monitoring and friends' conventionality mitigated the relationship between childhood disruptiveness and adolescence heavy substance use. Exposure to conventional friends further mediated the protective effect of parent monitoring. The postulated enhancement of attachment quality on the protective effect of parents or peer behaviors was not confirmed, but low attachment was related to heavier substance use in highly monitored disruptive boys. Parental monitoring, family attachment, and peer conventionality are factors amenable to intervention, and thus represent promising targets for future prevention strategies aimed at-risk boys. Our results underscore the importance of simultaneously addressing the behavioral and the affective dimensions in interventions with parents.

Differences and similarities in the serotonergic diathesis for suicide attempts and mood disorders: a 22-year longitudinal gene-environment study.

To investigate similarities and differences in the serotonergic diathesis for mood disorders and suicide attempts, we conducted a study in a cohort followed longitudinally for 22 years. A total of 1255 members of this cohort, which is representative of the French-speaking population of Quebec, were investigated. Main outcome measures included (1) mood disorders (bipolar disorder and major depression) and suicide attempts by early adulthood; (2) odds ratios and probabilities associated with 143 single nucleotide polymorphisms in 11 serotonergic genes, acting directly or as moderators in gene-environment interactions with childhood sexual or childhood physical abuse (CPA), and in gene-gene interactions; (3) regression coefficients for putative endophenotypes for mood disorders (childhood anxiousness) and suicide attempts (childhood disruptiveness). Five genes showed significant adjusted effects (HTR2A, TPH1, HTR5A, SLC6A4 and HTR1A). Of these, HTR2A variation influenced both suicide attempts and mood disorders, although through different mechanisms. In suicide attempts, HTR2A variants (rs6561333, rs7997012 and rs1885884) were involved through interactions with histories of sexual and physical abuse whereas in mood disorders through one main effect (rs9316235). In terms of phenotype-specific contributions, TPH1 variation (rs10488683) was relevant only in the diathesis for suicide attempts. Three genes contributed exclusively to mood disorders, one through a main effect (HTR5A (rs1657268)) and two through gene-environment interactions with CPA (HTR1A (rs878567) and SLC6A4 (rs3794808)). Childhood anxiousness did not mediate the effects of HTR2A and HTR5A on mood disorders, nor did childhood disruptiveness mediate the effects of TPH1 on suicide attempts. Of the serotonergic genes implicated in mood disorders and suicidal behaviors, four exhibited phenotype-specific effects, suggesting that despite their high concordance and common genetic determinants, suicide attempts and mood disorders may also have partially independent etiological pathways. To identify where these pathways diverge, we need to understand the differential, phenotype-specific gene-environment interactions such as the ones observed in the present study, using suitably powered samples.

[The mediating role of family functioning in the relationship between family adversity and preschoolers' social adjustment]. / Le rôle médiateur du fonctionnement familial dans la relation entre l'adversité familiale et l'adaptation sociale des enfants d'âge préscolaire.

Preschoolers' social adaptation is related to their degree of exposure to environnemental risks. However, the mechanisms through which the environmental risks operate their influence on social adaptation are still poorly documented. Thus, the first goal of this study is to investigate the main effect of family adversity on preschoolers' behavioral problems and attachment security. The second goal is to test the mediating effect of family functionning in the relationship between family adversity and behavioral problems or attachment security. Five hundred and seventy-two participants (n=572) were assessed on family adversity between the age of 5 and 42 months. Behavioral problems and family functionning were assesed at 42 months. Eighty of the participants were assessed on attachment security at the age of 48 months. The results show a main effect of family adversity on behavioral problems as well as a mediating effect of family functionning in the relationship of family adversity and behavioral problems. No significant effect was found for security of attachment.

Interrelations Between Maternal Smoking During Pregnancy, Birth Weight and Sociodemographic Factors in the Prediction of Early Cognitive Abilities.

Maternal prenatal smoking, birth weight and sociodemographic factors were investigated in relation to cognitive abilities of 1544 children (aged 3.5 years) participating in the Québec Longitudinal Study of Children's Development. The Peabody Picture Vocabulary Test (PPVT) was used to assess verbal ability, the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) block design test to assess visuospatial ability, and the Visually Cued Recall (VCR) task to assess short-term memory. Prenatal smoking was related to performance on the WPPSI-R, the PPVT, and the VCR, although it did not independently predict any cognitive ability after maternal education was taken into account. Birth weight was a more robust predictor of all outcome measures and independently predicted VCR-performance. Birth weight interacted significantly with family income and maternal education in predicting visuospatial ability, indicating a greater influence of birth weight under relatively poor socio-economic conditions. Parenting and family functioning mediated associations between maternal education/family income and cognitive task performance under different birth weight conditions, although there were indications for stronger effects under relatively low birth weight. We conclude that investigations of moderating and mediating effects can provide insights into which children are most at risk of cognitive impairment and might benefit most from interventions.

Salivary cortisol and aggression in a population-based longitudinal study of adolescent males.

Chronic antisocial behaviour in youth has been associated with cortisol, a measure of stress reactivity. However, some studies have found low cortisol levels, while others have found elevated cortisol levels. The present study compared variously defined aggressive subgroups for differences in salivary cortisol. A population-based sample of boys was followed longitudinally from childhood to adolescence. Assessments of different forms of antisocial behaviour were obtained from various informants at several points in time, and cortisol was collected at age 13. Higher cortisol levels were found in boys with conduct disorder (CD) than in boys without CD. In addition, boys with an aggressive form of CD had higher cortisol levels than boys who showed a covert form of CD. Furthermore, reactive aggression was strongly correlated with elevated cortisol. Adolescent boys with chronic reactive aggression and those who scored high on aggressive CD symptoms seem to have a more active hypothalamic-pituitary-adrenal system.

Prevention of injury by early socialization of aggressive behavior.

Frequent use of physical aggression by humans appears to reach its peak between 2 and 3 years of age. In the following years most children learn alternatives to physical aggression. Approximately 4% of children have high levels of physical aggression from early childhood to late adolescence. These children can be considered to show chronic physical aggression. They are at high risk of causing injuries to others and to themselves. They are also at high risk of many other co-morbid mental health conditions, school failure, substance abuse, depression, unemployment, spouse abuse, child abuse, and suicide. There is some evidence that, because of their risky style of behavior, they are also at high risk of many other medical conditions such as cardiovascular problems, cancer, and brain damage. Socialization of aggressive behavior during the preschool years should help prevent injuries throughout the life span.

Reactive and proactive aggression: predictions to physical violence in different contexts and moderating effects of parental monitoring and caregiving behavior.

This study aimed at (a) comparing the links of proactive and reactive aggression at 13 years of age to delinquency-related violence and dating violence at ages 16 and 17, and (b) examining the moderating effects of parental supervision, and mother's and father's warmth and caregiving behaviors on these links. Based on a sample of 525 Caucasian boys, the results showed that proactive aggression uniquely predicted delinquency-related violence, whereas reactive aggression uniquely predicted later dating violence. The relation between proactive aggression and delinquency-related violence, however, was moderated by parental supervision. The relation between reactive aggression and dating violence was moderated by mother's warmth and caregiving behavior. The implications of the findings for the theoretical and practical distinction between proactive and reactive aggression are discussed.

Predicting girls' conduct disorder in adolescence from childhood trajectories of disruptive behaviors.

OBJECTIVE: To examine girls' developmental trajectories of disruptive behaviors during the elementary school years and to predict conduct disorder symptoms and diagnosis in adolescence with trajectories of these behaviors. METHOD: The sample was 820 girls from the province of Quebec followed over 10 years (1986-1996). A semiparametric mixture model was used to describe girls' developmental trajectories of teacher-rated disruptive behaviors between the ages of 6 and 12 years. The trajectories were used to predict conduct disorder symptoms and diagnosis when the girls were on average 15.7 years. RESULTS: Four groups of girls following trajectories with distinct levels of disruptive behaviors were identified: a low, medium, medium-high, and high trajectory. Prediction with the trajectories indicated that girls on the medium, medium-high, and high trajectories reported a significantly higher number of conduct disorder symptoms in adolescence. However, only the girls on the medium-high and high trajectories were at significantly higher risk to meet DSM-III-R criteria for conduct disorder, compared with girls in the low group (odds ratio: 4.46). More than two thirds of the girls with conduct disorder were in the medium or higher-level trajectories. CONCLUSION: The results suggest that there is an early-onset type of conduct disorder in girls.

Prevalence of psychiatric diagnoses and the role of perceived impairment: findings from an adolescent community sample.

The present study examined psychiatric functioning in a community sample of adolescents aged 14 to 17 years (average age of 15 years). We administered the Diagnostic Interview Schedule for Children-2.25 (DISC-2.25) to 1,201 adolescents and their mothers to obtain prevalence estimates of DSM-III-R disorders and the amount of perceived impairment associated with these disorders. While adolescent females reported a significantly higher prevalence of psychiatric disorders than males (15.5% vs. 8.5%), mothers indicated no sex difference. Compared with adolescent males, females had significantly higher rates of internalizing, anxiety. and depressive disorders. In contrast, the prevalence of externalizing disorders was significantly higher among adolescent males. The inclusion of an impairment criterion had a significant impact in reducing the prevalence rates of overall psychiatric disorders. This reduction occurred mainly through impairment's effects on internalizing disorders, specifically anxiety-based disorders (i.e., simple and social phobia). Given the limited research on the effect of impairment on the prevalence of adolescent psychiatric disorders, future work in this area seems warranted.

Modeling interinformant agreement in the absence of a "gold standard".

Epidemiological surveys of child and adolescent mental disorders often rely on multiple informants to get a complete diagnostic picture. A consistent finding in the literature is that different informants often do not identify the same children as being disordered. However, because current strategies for estimating interinformant agreement often involve categorizing children using less than perfectly sensitive and/or specific symptoms, biased estimates of interinformant agreement are likely. The aim of this report was to illustrate how latent class analysis (LCA) can be used to model interinformant agreement in the absence of a "gold standard". The proposed model consists of informant-specific latent variables each made up of two or more latent classes corresponding to different levels of symptomatology. Unlike most previous applications of LCA this model allows us to model the extent to which the prevalence of the disorder is the same across informants; and, in addition, the association between informants. The data set comes from a prospective longitudinal study of 2,264 children from Quebec (1,155 boys and 1,109 girls). In grade 2, teachers and mothers independently rated each child on three physical aggression behavior symptoms. We satisfactorily accounted for the cross-classification of the behavior symptoms by postulating the existence of two latent variables--one for each informant each made up of three latent classes of children: low-, medium-, and high-aggressive. The results showed that the prevalence of low- and medium-aggressive children in the population differed from teacher to mother, but that the prevalence of high-aggressive children did not. We found that the association between teacher and mother was large and positive and did not vary according to the child's physical aggression state or gender; in contrast, the association between physical aggression and gender was not the same for mother and teacher. Limitations and other potential applications of the proposed model are discussed.