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 thorough investigation of the bifactor model of psychopathology in a representative birth cohort: Testing internal and predictive validity to inform models of comorbidity.

This study used symptom dimensions reflecting DSM-V internalizing, externalizing, eating disorders, and substance use (SU) and related problems to thoroughly investigate the structure of psychopathology in mid-adolescence (15 and 17 years, N = 1,515, 52% female). Compared to other hierarchical configurations (unidimensional, correlated factors, or higher-order model), a bifactor model of psychopathology wherein all first-order symptom dimensions loaded onto a second-order general psychopathology factor (P factor) and one of three, second-order specific internalizing, externalizing, or SU factors, best captured the structure of the psychopathology in mid-adolescence. This bifactor model was then used to predict several distinct mental health disorders and alcohol use disorder (AUD) at 20 years, via a structural equation model (SEM). The P factor (bifactor model) was associated with all but one outcome (suicidal ideation without an attempt), at 20 years. Controlling for the P factor, there were no additional, positive, temporal cross-associations (i.e., between mental health (mid-adolescence) and AUD at 20 years, or between SU (mid-adolescence) and mental health problems at 20 years). These results are bolstered by findings from a well-fitting correlated factors model. Namely, when mid-adolescent psychopathology was modeled using an adjusted correlated factors model, associations with outcomes at 20 years were largely masked, with no significant partial, temporal cross-associations. Thus, collectively, findings indicate that comorbidity between SU and mental health in youth may be largely attributable to an underlying liability to experience both problems (i.e., P factor). Ultimately, results support targeting the common liability to psychopathology in the prevention of later mental health problems and AUD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

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 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.

Quebec, Scotland, and substate governments' roles in Canadian and British trade policy: Lessons to be learned.

Following Brexit (the withdrawal of the UK from the EU and the European Atomic Energy Community at the end of 31 January 2020), the British government stated that it hoped to reach a new trade agreement with Canada to be modelled after the Canada-EU Comprehensive Economic and Trade Agreement, the first free-trade deal for which Canadian provinces were directly involved at every stage of negotiations. In the UK, while there are mechanisms for the involvement of devolved regions in European policy, there is no clear constitutional doctrine as to the roles they should play in elaborating trade policy more generally. Moreover, the asymmetric nature of the UK's devolution system complicates the involvement of its devolved governments in trade negotiations. By providing a specific focus on the cases of Quebec and Scotland, this article provides a comparison of substate governments' roles in trade negotiation and trade promotion. It concludes that, while there seems to be only limited scope for substate governments' formal input into future trade negotiations, their trade and investment promotion organizations allow them to pursue different objectives over trade outcomes within a unified national framework.

Associations between developmental trajectories of peer victimization, hair cortisol, and depressive symptoms: a longitudinal study.

BACKGROUND: Peer victimization has been associated with long-lasting risks for mental health. Prior research suggests that stress-related systems underlying adaptation to changing environments may be at play. To date, inconsistent findings have been reported for the hypothalamic-pituitary-adrenal (HPA) axis, and its end product cortisol. This study tested whether peer victimization was associated with hair cortisol concentrations (HCC), and whether this association varied according to sex, timing, and changes in exposure. We also examined whether peer victimization differentially predicted depressive symptoms according to HCC. METHODS: The sample comprised 556 adolescents (42.0%; 231 males) who provided hair for cortisol measurement at 17 years of age. Peer victimization was reported at seven occasions between the ages of 6 and 15 years. RESULTS: Peer victimization was nonlinearly associated with HCC for boys only, whereas changes in peer victimization were related to HCC for boys and girls. Peer victimization predicted more depressive symptoms for all participants, except those with lower HCC. CONCLUSIONS: Our findings provide further support for persistent dysregulation of the HPA axis following exposure to chronic adversity, of which the expression may change according to sex and the severity of victimization.

A person-centered approach to studying associations between psychosocial vulnerability factors and adolescent depressive symptoms and suicidal ideation in a Canadian longitudinal sample.

This study used a person-centered approach to identify subgroups of adolescents who are at risk for depression and suicidal ideation. Latent class analysis was first applied to 1,290 adolescents from a Canadian cohort study in order to identify latent vulnerability subtypes based on 18 psychosocial vulnerability factors. Logistic regression analyses were conducted to study the associations between class membership and depressive symptoms and suicidal ideation 2 years later. The moderating role of sex in the associations between latent classes and depressive symptoms was explored. Five latent classes were identified: Low Vulnerability (42%), Substance Use Only (13%), Moderate Vulnerability (28%), Conduct Problems (8%) and High Vulnerability (9%). Compared with the Low Vulnerability class, the probabilities of presenting depressive symptoms were higher for the Substance Use Only class, OR = 1.93, 95% CI [1.21, 3.06], the Moderate Vulnerability class, OR = 2.96, 95% CI [2.09, 4.20], the Conduct Problems class, OR = 3.03, 95% CI [1.84, 4.98], and the High Vulnerability class, OR = 5.4, 95% CI [3.42, 8.53]. Furthermore, interaction effects with sex were identified in relation to depressive symptoms only. The probability of presenting suicidal ideation was higher only for the High Vulnerability class, OR = 4.51, 95% CI [2.41, 8.43]. This study highlights the importance of a person-centered perspective that considers both vulnerability subtypes and sex because these associations are complex rather than linear or additive.

Maternal depression in early childhood and child emotional and behavioral outcomes at school age: examining the roles of preschool childcare quality and current maternal depression symptomatology.

Recent studies have shown that the association between maternal depression and child outcome can be moderated by children's experience of childcare (e.g., daycare) during early childhood (0-5 years). We also know that maternal depression in the child's early years has long-term associations with child development. However, the moderating role of childcare quality on long-term associations between maternal depression and child outcome has not been thoroughly investigated. This article examined longitudinal associations between probable maternal depression (PMD) during early childhood (0-5 years) and childcare quality on children's emotional and behavioral development at the age of 7-8 years (N = 207). Childcare quality was evaluated through observations within the settings. PMD during early childhood was assessed using complementary information from interviews conducted with the mother and current maternal symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Internalizing and externalizing behaviors were reported by the mother, father and the child at age 7-8 years. Results indicate that when mothers reported clinically relevant depression in early childhood, 7-8-year-old children demonstrate fewer behavioral problems if they attended a higher quality childcare setting. The moderating role of childcare quality remained after considering current maternal depression symptoms. Therefore, it is important to ensure high-quality childcare during early childhood to optimize child development.

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

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

Heterogeneity in the development of proactive and reactive aggression in childhood: Common and specific genetic - environmental factors.

BACKGROUND: Few studies are grounded in a developmental framework to study proactive and reactive aggression. Furthermore, although distinctive correlates, predictors and outcomes have been highlighted, proactive and reactive aggression are substantially correlated. To our knowledge, no empirical study has examined the communality of genetic and environmental underpinning of the development of both subtypes of aggression. The current study investigated the communality and specificity of genetic-environmental factors related to heterogeneity in proactive and reactive aggression's development throughout childhood. METHODS: Participants were 223 monozygotic and 332 dizygotic pairs. Teacher reports of aggression were obtained at 6, 7, 9, 10 and 12 years of age. Joint development of both phenotypes were analyzed through a multivariate latent growth curve model. Set point, differentiation, and genetic maturation/environmental modulation hypotheses were tested using a biometric decomposition of intercepts and slopes. RESULTS: Common genetic factors accounted for 64% of the total variation of proactive and reactive aggression's intercepts. Two other sets of uncorrelated genetic factors accounted for reactive aggression's intercept (17%) on the one hand, and for proactive (43%) and reactive (13%) aggression's slopes on the other. Common shared environmental factors were associated with proactive aggression's intercept (21%) and slope (26%) and uncorrelated shared environmental factors were also associated with reactive aggression's slope (14%). Common nonshared environmental factors explained most of the remaining variability of proactive and reactive aggression slopes. CONCLUSIONS: A genetic differentiation hypothesis common to both phenotypes was supported by common genetic factors associated with the developmental heterogeneity of proactive and reactive aggression in childhood. A genetic maturation hypothesis common to both phenotypes, albeit stronger for proactive aggression, was supported by common genetic factors associated with proactive and reactive aggression slopes. A shared environment set point hypothesis for proactive aggression was supported by shared environmental factors associated with proactive aggression baseline and slope. Although there are many common features to proactive and reactive aggression, the current research underscores the advantages of differentiating them when studying aggression.

Child-care quality moderates the association between maternal depression and children's behavioural outcome.

BACKGROUND: Maternal depression is a risk factor for adverse outcomes in the child, including emotional and behavioural difficulties. There is evidence that child care attendance during the preschool years may moderate associations between familial risk factors and child outcome. However, the possibility that high-quality child care provides protection for children exposed to maternal depression or that low-quality child care provides additional risk has not been investigated. We study whether child-care quality moderates the association between probable history of maternal depression (PMD) and child behavioural and emotional outcomes over the preschool period. METHODS: Within a longitudinal study, we examined PMD (no depression; clinical PMD before the child's birth; subclinical PMD from 0 to 5 years; clinical PMD from 0 to 5 years), child-care quality and child emotional and behavioural difficulties at the ages of 2, 3 and 4 years. Child-care quality was evaluated in settings, and trajectories were calculated to reflect (a) global quality and (b) two quality subfactors: 'Teaching and interactions' and 'Provision for learning'. Data were analysed for 264 families. RESULTS: Significant interactions emerged between clinical PMD and global quality of child care for children's externalising behaviour (b = -.185, p = .008), more specifically hyperactivity/inattention (b = -.237, p = .002). In the context of clinical PMD, children attending high-quality child care presented fewer difficulties than those attending a low-quality care. Child-care quality was not associated with outcomes for children whose mothers did not report a PMD or a PMD before their birth. CONCLUSIONS: In the context of PMD, high-quality child care was associated with fewer behavioural problems and may thus constitute a protective factor.

Persistence and innovation effects in genetic and environmental factors in negative emotionality during infancy: A twin study.

BACKGROUND: Difficult temperament in infancy is a risk factor for forms of later internalizing and externalizing psychopathology, including depression and anxiety. A better understanding of the roots of difficult temperament requires assessment of its early development with a genetically informative design. The goal of this study was to estimate genetic and environmental contributions to individual differences in infant negative emotionality, their persistence over time and their influences on stability between 5 and 18 months of age. METHOD: Participants were 244 monozygotic and 394 dizygotic twin pairs (49.7% male) recruited from birth. Mothers rated their twins for negative emotionality at 5 and 18 months. Longitudinal analysis of stability and innovation between the two time points was performed in Mplus. RESULTS: There were substantial and similar heritability (approximately 31%) and shared environmental (57.3%) contributions to negative emotionality at both 5 and 18 months. The trait's interindividual stability across time was both genetically- and environmentally- mediated. Evidence of innovative effects (i.e., variance at 18 months independent from variance at 5 months) indicated that negative emotionality is developmentally dynamic and affected by persistent and new genetic and environmental factors at 18 months. CONCLUSIONS: In the first two years of life, ongoing genetic and environmental influences support temperamental negative emotionality but new genetic and environmental factors also indicate dynamic change of those factors across time. A better understanding of the source and timing of factors on temperament in early development, and role of sex, could improve efforts to prevent related psychopathology.

Childhood trajectories of inattention-hyperactivity and academic achievement at 12 years.

Few prospective studies spanning early childhood to early adolescence have examined separately the contribution of inattention and hyperactivity to academic achievement. The aim of the present study was to investigate whether the developmental trajectories of inattention and hyperactivity symptoms during early and middle childhood are independently associated with academic achievement at age 12 years. The independent associations between inattention and hyperactivity trajectories during early and middle childhood and academic performance at age 12 years were examined in a population-based longitudinal birth cohort (n = 2120). In adjusted analyses, high early childhood inattention trajectories were associated with teacher-rated academic performance in reading, writing and mathematics and with government exam score in writing. High and moderate inattention trajectories during middle childhood predicted lower performance on both teacher-rated academic performance and government exam scores in reading, writing, and mathematics. Hyperactivity was not a consistent predictor of educational outcomes. Childhood inattention symptoms rather than hyperactivity carry risk of poor educational outcomes at age 12 years. Children with high levels of inattention can be identified during the preschool years. Prevention programs supporting the development of attentional capacities and executive functions could help reduce the negative consequences of inattention.