Intergenerational transmission of genetic risk for hyperactivity and inattention. Direct genetic transmission or genetic nurture?

Background: Hyperactivity and inattention, the symptoms of ADHD, are marked by high levels of heritability and intergenerational transmission. Two distinct pathways of genetic intergenerational transmission are distinguished: direct genetic transmission when parental genetic variants are passed to the child's genome and genetic nurture when the parental genetic background contributes to the child's outcomes through rearing environment. This study assessed genetic contributions to hyperactivity and inattention in childhood through these transmission pathways. Methods: The sample included 415 families from the Quebec Newborn Twin Study. Twins' hyperactivity and inattention were assessed in early childhood by parents and in primary school by teachers. The polygenic scores for ADHD (ADHD-PGS) and educational attainment (EA-PGS) were computed from twins' and parents' genotypes. A model of intergenerational transmission was developed to estimate (1) the contributions of parents' and children's PGS to the twins' ADHD symptoms and (2) whether these variances were explained by genetic transmission and/or genetic nurture. Results: ADHD-PGS explained up to 1.6% of the variance of hyperactivity and inattention in early childhood and primary school. EA-PGS predicted ADHD symptoms at both ages, explaining up to 1.6% of the variance in early childhood and up to 5.5% in primary school. Genetic transmission was the only significant transmission pathway of both PGS. The genetic nurture channeled through EA-PGS explained up to 3.2% of the variance of inattention in primary school but this association was non-significant. Conclusions: Genetic propensities to ADHD and education predicted ADHD symptoms in childhood, especially in primary school. Its intergenerational transmission was driven primarily by genetic variants passed to the child, rather than by environmentally mediated parental genetic effects. The model developed in this study can be leveraged in future research to investigate genetic transmission and genetic nurture while accounting for parental assortative mating.

Genetics of environmental sensitivity and its association with variations in emotional problems, autistic traits, and wellbeing.

Greater environmental sensitivity has been associated with increased risk of mental health problems, especially in response to stressors, and lower levels of subjective wellbeing. Conversely, sensitivity also correlates with lower risk of emotional problems in the absence of adversity, and in response to positive environmental influences. Additionally, sensitivity has been found to correlate positively with autistic traits. Individual differences in environmental sensitivity are partly heritable, but it is unknown to what extent the aetiological factors underlying sensitivity overlap with those on emotional problems (anxiety and depressive symptoms), autistic traits and wellbeing. The current study used multivariate twin models and data on sensitivity, emotional problems, autistic traits, and several indices of psychological and subjective wellbeing, from over 2800 adolescent twins in England and Wales. We found that greater overall sensitivity correlated with greater emotional problems, autistic traits, and lower subjective wellbeing. A similar pattern of correlations was found for the Excitation and Sensory factors of sensitivity, but, in contrast, the Aesthetic factor was positively correlated with psychological wellbeing, though not with emotional problems nor autistic traits. The observed correlations were largely due to overlapping genetic influences. Importantly, genetic influences underlying sensitivity explained between 2 and 12% of the variations in emotional problems, autistic traits, and subjective wellbeing, independent of trait-specific or overlapping genetic influences. These findings encourage incorporating the genetics of environmental sensitivity in future genomic studies aiming to delineate the heterogeneity in emotional problems, autistic traits, and wellbeing.

A Clinical Practice Guide to Enhance Physical Activity Participation for Children with Developmental Coordination Disorder in Canada.

Purpose: This clinical practice guide (CPG) aims to provide evidence-based recommendations for promoting and enhancing the participation and integration of children with developmental coordination disorder (DCD) into physical activities that take place in the home, school, community, or rehabilitation clinic contexts. Methods: A panel of key stakeholders relevant to these contexts (parents, instructors, rehabilitation professionals) developed evidence-based recommendations using a consensus methodology after reviewing results from a recent systematic review of relevant literature. The quality of the evidence on which the recommendations were based was evaluated (2011 Oxford Centre for Evidence-Based Medicine Levels of Evidence scale) as was the strength of the final CPG recommendations (American Society of Plastic Surgeons Grade Recommendation Scale). Results: Recommendations (n = 50; 36% supported by robust, empirically derived evidence) for the different stakeholder groups fell into three categories: 1) Choose an appropriate activity for your child, 2) Harmonize the activity with the child's interests and abilities, and 3) Help the child learn new movements prior to the activity. Conclusions: This comprehensive CPG provides concrete recommendations, based on the currently available evidence, that can be used by stakeholders to address the physical activity participation and integration needs of children with DCD in a variety of contexts.

Objectif: ces directives cliniques visent à fournir des recommandations basées sur les données probantes pour promouvoir et améliorer la participation et l'intégration des enfants ayant un trouble développemental de la coordination (TDC) à des activités physiques qui se déroulent à la maison, à l'école, dans la communauté ou dans des cliniques de réadaptation. Méthodologie: un groupe d'intervenants clés dans ces contextes (parents, entraineurs, professionnels de la réadaptation) a préparé des recommandations fondées sur des données probantes au moyen d'une méthodologie de consensus, après avoir révisé les résultats d'une récente analyse systématique de publications pertinentes. La qualité des données probantes sur laquelle reposent les recommandations a été évaluée (échelle de qualité des preuves de l'Oxford Centre for Evidence-Based Medicine de 2011) de même que les catégories des recommandations définitives tirées des directives (échelle des catégories de recommandations de l'American Society of Plastic Surgeons). Résultats: les recommandations (n = 50; 36 % soutenues par des données probantes empiriques vigoureuses) des divers groupes d'intervenants se déclinaient en trois catégories : 1) choisir une activité appropriée pour l'enfant, 2) harmoniser l'activité selon les intérêts et les capacités de l'enfant, 3) aider l'enfant à s'approprier de nouveaux mouvements pour aller vers l'activité. Conclusions: ces directives cliniques complètes fournissent des recommandations concrètes d'après les données probantes disponibles, que peuvent utiliser les intervenants pour aborder la participation à l'activité physique et les besoins d'intégration des enfants ayant un TDC dans divers contextes.

A cross-lagged twin study of emotional symptoms, social isolation and peer victimisation from early adolescence to emerging adulthood.

BACKGROUND: Emotional symptoms, such as anxiety and depressive symptoms, are common during adolescence, often persist over time, and can precede the emergence of severe anxiety and depressive disorders. Studies suggest that a vicious cycle of reciprocal influences between emotional symptoms and interpersonal difficulties may explain why some adolescents suffer from persisting emotional symptoms. However, the role of different types of interpersonal difficulties, such as social isolation and peer victimisation, in these reciprocal associations is still unclear. In addition, the lack of longitudinal twin studies conducted on emotional symptoms during adolescence means that the genetic and environmental contributions to these relationships during adolescence remain unknown. METHODS: Participants (N = 15,869) from the Twins Early Development Study completed self-reports of emotional symptoms, social isolation and peer victimisation at 12, 16 and 21 years old. A phenotypic cross-lagged model examined reciprocal associations between variables over time, and a genetic extension of this model examined the aetiology of the relationships between variables at each timepoint. RESULTS: First, emotional symptoms were reciprocally and independently associated with both social isolation and peer victimisation over time, indicating that different forms of interpersonal difficulties uniquely contributed to emotional symptoms during adolescence and vice versa. Second, early peer victimisation predicted later emotional symptoms via social isolation in mid-adolescence, indicating that social isolation may constitute an intermediate pathway through which peer victimisation predicts longer-term emotional symptoms. Finally, individual differences in emotional symptoms were mostly accounted for by non-shared environmental factors at each timepoint, and both gene-environment and individual-specific environmental mechanisms were involved in the relationships between emotional symptoms and interpersonal difficulties. CONCLUSIONS: Our study highlights the necessity to intervene early in adolescence to prevent the escalation of emotional symptoms over time and to consider social isolation and peer victimisation as important risk factors for the long-term persistence of emotional symptoms.

Factors associated with anxiety disorder comorbidity.

BACKGROUND: Anxiety and depressive disorders often co-occur and the order of their emergence may be associated with different clinical outcomes. However, minimal research has been conducted on anxiety-anxiety comorbidity. This study examined factors associated with anxiety comorbidity and anxiety-MDD temporal sequence. METHODS: Online, self-report data were collected from the UK-based GLAD and COPING NBR cohorts (N = 38,775). Logistic regression analyses compared differences in sociodemographic, trauma, and clinical factors between single anxiety, anxiety-anxiety comorbidity, anxiety-MDD (major depressive disorder) comorbidity, and MDD-only. Additionally, anxiety-first and MDD-first anxiety-MDD were compared. Differences in familial risk were assessed in those participants with self-reported family history or genotype data. RESULTS: Anxiety-anxiety and anxiety-MDD had higher rates of self-reported anxiety or depressive disorder diagnoses, younger age of onset, and higher recurrence than single anxiety. Anxiety-MDD displayed greater clinical severity/complexity than MDD only. Anxiety-anxiety had more severe current anxiety symptoms, less severe current depressive symptoms, and reduced likelihood of self-reporting an anxiety/depressive disorder diagnosis than anxiety-MDD. Anxiety-first anxiety-MDD had a younger age of onset, more severe anxiety symptoms, and less likelihood of self-reporting a diagnosis than MDD-first. Minimal differences in familial risk were found. LIMITATIONS: Self-report, retrospective measures may introduce recall bias. The familial risk analyses were likely underpowered. CONCLUSIONS: Anxiety-anxiety comorbidity displayed a similarly severe and complex profile of symptoms as anxiety-MDD but distinct features. For anxiety-MDD, first-onset anxiety had an earlier age of onset and greater severity than MDD-first. Anxiety disorders and comorbidity warrant further investigation and attention in research and practice.

Polygenic risk score and peer victimisation independently predict depressive symptoms in adolescence: results from the Quebec Longitudinal Study of Children Development.

BACKGROUND: Peer victimisation has been associated with depressive symptoms during adolescence, however not all peer victimised adolescents will exhibit such symptoms. This study tested whether having a genetic predisposition to developing depression increased the risk of experiencing depressive symptoms in peer victimised youth. To date, no study has explored such gene-environment interaction using a polygenic risk score for depression (PRS-depression) in the context of peer victimisation and depressive symptoms in adolescence. METHODS: The sample included 748 participants born in 1997/98 from the Quebec Longitudinal Study of Child Development with genotype data and prospectively collected information on peer victimisation (12-13 years) obtained from both self- and teacher-reports, as well as self-reported depressive symptoms (15-17 years). The PRS-depression was based on the genome-wide association meta-analysis of broad depression by Howard et al. (2019). RESULTS: Self- and teacher-reported peer victimisation in early adolescence were both associated with depressive symptoms in adolescence (ß = 0.34, p < .001; ß = 0.14, p = .001 respectively), and this association remained significant when accounting for PRS-depression (ß = 0.33, p < .001; ß = 0.13, p = .002 respectively). PRS-depression was independently associated with depressive symptoms, but there was no significant PRS-depression by peer victimisation interaction (self-reported and teacher-reported). PRS-depression was correlated with self-reported, but not teacher-reported, peer victimisation. CONCLUSIONS: Our findings suggested that a partial measure of an individual's genetic predisposition to depression, as measured by PRS-depression, and being exposed to peer victimisation (self- and teacher-reported) were independently associated with depressive symptoms in adolescence. Furthermore, PRS-depression did not exacerbate the risk of depressive symptoms among adolescents who had been peer victimised. Lastly, we found evidence of a gene-environment correlation between PRS-depression and self-reported peer victimisation. Future studies are needed to replicate this finding and to further understand the role of genetic predispositions in experiencing depressive symptoms following peer victimisation.

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.

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.

A multi-informant and multi-polygenic approach to understanding predictors of peer victimisation in childhood and adolescence.

Introduction: Peer victimisation is a prevalent occurrence in childhood and adolescence and can often have long-lasting consequences. Previous research using polygenic scores (PGSs) have revealed various genetic vulnerabilities as predictive of victimisation in childhood. However, findings were based on self-report and may therefore be influenced by varying self-perceptions. Previous investigations also focused on average victimisation across childhood, and thus do not capture variability in polygenic predictability over time. The present study, therefore, aimed to investigate associations between PGSs and victimisation using separate and combined reports from teachers and peers in childhood, as well as self-reports in later adolescence to explore trajectories of victimisation. Methods: Data were derived from the Quebec Newborn Twin Study. Participants were assessed for victimisation using self-reports from 7 to 17 years and using teacher ratings and peer nominations between 7 and 10 years (n = 536). Ten PGSs related to mental health, cognitive abilities and physical traits were examined as possible predictors of victimisation using linear regressions and growth curve models. Results: Findings revealed that PGSs associated with victimisation are consistent across informants, but to varying extent according to estimated effect sizes. Self-reported victimisation was predicted by PGSs related to mental health, while PGSs related to cognitive and physical traits had larger effect estimates when predicting teacher- and peer-reported victimisation. The PGS for educational attainment was consistently negatively associated with victimisation across informants, producing the largest effect estimates (ß = -.104, 95% CI = -.169 to -.039) when predicting a multi-informant measure of victimisation. No PGS predicted changes in victimisation over time. Conclusion: While the PGS for educational attainment is a robust predictor of victimisation, many PGSs are differentially associated with victimisation depending on the informant. Such findings highlight the need to pay close attention to the phenotypic assessment of victimisation, and show that using multiple informants can both strengthen and provide unique insight into how associations may occur.

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.

Social wariness, preference for solitude, and peer difficulties in middle childhood: A longitudinal family-informed study.

The present study examined, within a longitudinal family-informed design and across middle childhood, the predictive associations between preference for solitude and social wariness, two forms of social withdrawal, and peer difficulties. Specifically, preference for solitude, rather than social wariness, was expected to predict peer victimization and rejection, two aspects of peer difficulties. A total of 1,014 children from the Quebec Newborn Twin Study were assessed by teachers and peers at ages 6, 7, and 10 years. Multilevel analyses conducted across three levels, between family, within family, and within person, revealed that preference for solitude, rather than social wariness, increased the risk for peer difficulties in terms of both peer victimization and peer rejection. Specifically, preference for solitude was systematically associated with peer rejection starting at age 6 years and became progressively associated with peer victimization over time. This pattern was found both between and within families. In addition, the predictive association with peer rejection was found within genetically identical, monozygotic twin pairs, suggesting that this predictive association existed after taking into account genetic vulnerabilities. Social wariness was systematically unrelated to peer difficulties. These findings suggest that preference for solitude, rather than social wariness, is a risk factor for peer difficulties. They underscore the relevance of distinguishing these dimensions of social withdrawal and illustrate the usefulness of a family-informed design to document the processes underlying childhood social adjustment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The genetic and environmental hierarchical structure of anxiety and depression in the UK Biobank.

BACKGROUND: Anxiety and depressive disorders can be classified under a bidimensional model, where depression and generalized anxiety disorder are represented by distress and the other anxiety disorders, by fear. The phenotypic structure of this model has been validated, but twin studies only show partial evidence for genetic and environmental distinctions between distress and fear. Moreover, the effects of genetic variants are mostly shared between anxiety and depression, but the genome-wide genetic distinction between distress and fear remains unexplored. This study aimed to examine the degree of common genetic variation overlap between distress and fear, and their associations with the psychosocial risk factors of loneliness and social isolation. METHODS: We used genome-wide data from 157,366 individuals in the UK Biobank who answered a mental health questionnaire. RESULTS: Genetic correlations indicated that depression and generalized anxiety had a substantial genetic overlap, and that they were genetically partially distinct from fear disorders. Associations with loneliness, but not social isolation, showed that loneliness was more strongly associated with both distress disorders than with fear. CONCLUSIONS: Our findings shed light on genetic and environmental mechanisms that are common and unique to distress and fear and contribute to current knowledge on individuals' susceptibility to anxiety and depression.

Genetic influences on treatment-seeking for common mental health problems in the UK biobank.

The majority of those who experience clinical anxiety and/or depressive symptoms in the population do not receive treatment. Studies investigating inequalities in treatment outcomes rarely consider that individuals respond differently to their experience of the environment. Much of our environment is under genetic influence, via our behaviour, whereby individuals actively select their experiences. If genes influence who seeks and receives treatment, selection bias will confound genomic studies of treatment response. Furthermore, if some individuals are at high genetic risk of needing but not commencing treatment, then greater efforts could be made to engage them. The role of common genetic variation on four lifetime treatment-seeking behaviours (treatment-seeking, treatment-receipt, self-help, self-medication with alcohol/drugs) was examined in participants of the UK Biobank (sample size range: 48,106 - 75,322). Treatment-related behaviours were only modestly heritable in these data. Nonetheless, genetic correlations reveal substantial genetic overlap between lifetime treatment-related behaviours and psychiatric disorders, symptoms and behavioural traits. To our knowledge, this is the first study to examine genetic influences on treatment-related behaviours. Further work is required to determine whether genetic factors could be used alongside clinical, social and demographic factors to identify at risk groups and inform strategies which target early intervention.

The Genetic and Environmental Etiology of Shyness Through Childhood.

The objective of this study was to examine the genetic and environmental contributions to shyness throughout the school-age period. Participants were 553 twin pairs from the ongoing prospective longitudinal Quebec Newborn Twin Study. Teacher-rated measures of shyness were collected at five time-points from age 6-12 years. On average, shyness was moderately stable over time (r = 0.23-0.33) and this stability was almost entirely accounted for by genetic factors. Genetic factors at age 6 accounted for 44% of individual differences and these early genetic factors also explained individual differences at all subsequent ages (6-22%). Non-shared environmental factors explained most of individual differences at single time-points (51-63%), and did not account for stability in shyness. Contributions of shared environment were not significant. Our results suggest that the stability in shyness is mostly accounted for by early and persistent genetic contributions.