Chair:
Dr Isabelle Ouellet-Morin – University of Montreal, Montreal, Canada
Discussant:
Dr Megan Gunnar – University of Minnesota, Minnesota, USA
Symposium Presenters:
- Marie-Pier Larose, Turku University
- Christina Cantave, University of Groningen
- Isabelle Ouellet-Morin, University of Montreal
- Patricia Pelufo Silveira, McGill University
Full Description of the Symposium
Early life adversity has the potential to influence brain development, biological systems, attitudes, and behaviors, which is hypothesized to subsequently affect physical and mental health in adulthood. However, the effects of these experiences vary across different domains of functioning and may not be uniform across individuals, necessitating further investigation into the genetic underpinnings of developmental outcomes through comprehensive, developmentally sensitive research designs. We also need to expand our search into both the endogenous and exogenous causal pathways at play, ranging from molecular mechanisms to the structural and broader social influences that shape life within our society. In the first presentation, Dr Larose will present the contributions of a polygenic score (PGS) for externalizing behaviors and latent profiles of neighborhood deprivation on conduct disorders during adolescence and show that the PGS and neighborhoods with crime and low-quality infrastructures both additively predict conduct disorders. Next, Dr Cantave will offer additional evidence that genetic predispositions for internalizing and externalizing problems are associated with higher risk encounter childhood adversity, although no such association is noted for peri-natal adversity. Delving deeper into the possibility that genetic factors may be confounded with early-life adversity, Dr. Ouellet-Morin will show that childhood maltreatment is more likely to arise among children with a genetic predisposition for aggression and shed light on how these experiences partly explain how the PGS predict developmental trajectories of global and reactive aggression during adolescence. Finally, using advanced genomics and translational animal models, Dr Pelufo Silveira will show that brain-specific gene networks responsive to early stress and insulin, have a sex-dependent modulation of adversity response mediated by brain insulin, particularly in dopaminergic pathways influencing behavior and decision-making.
Abstract for Presentation 1
DOES NEIGHBORHOOD DEPRIVATION INTERACT WITH POLYGENIC INDICES FOR EXTERNALIZING PROBLEMS TO PREDICT ADOLESCENT CONDUCT PROBLEMS?
Assessing the contribution of neighborhood quality on adolescent conduct problems (CD) is difficult, as the neighborhood in which children grow up is associated with their parents’ socioeconomic status, which is influenced by the environment and genetics. We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC, N= 4,221) to examine whether neighborhood deprivation interacted with adolescents’ genetic predispositions for externalizing problems to predict CD at age 15. We used latent profile analysis to create deprivation profiles at age 13 based on census information and found four neighborhood profiles based on their levels of crime, education, income and infrastructure quality. We created children’s and mothers’ polygenic scores (PGS) – an index of genetic liability – for externalizing problems. Using linear regression, we tested the direct and interactive effect of neighborhood deprivation on adolescents’ CD while adjusting for a set of sociodemographic covariates and for mothers’ PGS for externalizing problems. We found a significant direct effect of the adolescents’ PGS on CD (B = 0.093, p <0.001) as well as a direct effect of neighborhood deprivation where adolescents living in a neighborhood high in crime and with low-quality infrastructure had significantly higher levels of CD (B = 0.195, p <0.001). We found no interactive effect between neighborhood deprivation and adolescent PGS. Our results suggest that health-promoting urban planning initiatives could have a universal effect in highly deprived neighborhoods. However, more targeted initiatives may be needed for adolescents with high levels of genetic predispositions, regardless of where they grow up.
Abstract for Presentation 2
UNRAVELING THE EFFECT OF EARLY ADVERSITY ON ADOLESCENT SOCIAL SUPPORT: DO GENETIC PREDISPOSITIONS AND TIMING OF EXPOSURE MATTER?
Perceived social support is a known contributor of youth resilience. However, individual differences exist in youths’ ability to access social support, which may be related to their genetic predispositions and early life experiences. However, to date, no studies have tested this hypothesis. We examined how early adversity and genetic predispositions for educational attainment, internalizing, and externalizing behaviours uniquely and jointly predict youth reports of support from their parents and friends at age 11. We tested whether these associations varied according to the timing of adversity. Participants were drawn from a prospective study of Dutch adolescents. Adversity was measured during the pre-and postnatal period and childhood (ages 0–11) through Preventive Child Healthcare records and parental interviews at age 11. Participants genotype data were used to derive polygenic scores. Social support from mothers (n=1634), fathers (n=1609) and friends (n=1634) were self-reported at age 11. We found that higher genetic predispositions for internalizing and externalizing problems were associated with greater exposure to childhood adversity but were otherwise unrelated to social support. Conversely, exposure to pre-postnatal adversity was related to higher support from mothers during adolescence, while childhood adversity was associated with less support from fathers. These associations did not vary according to youths’ genetic predispositions. These findings suggest that youths’ genetic liabilities to problematic behaviours correlate with exposure to childhood adversity, but not with pre-and postnatal adversity. Further research should examine these gene-environment correlations across different developmental stages as well as their underlying mechanisms.
Abstract for Presentation 3
GENE-ENVIRONMENTAL CORRELATION BETWEEN CHILD MALTREATMENT AND DEVELOPMENTAL TRAJECTORIES OF AGGRESSION: A PROSPECTIVE STUDY.
A strong consensus exists regarding the influence genes and environments exert on aggression behaviors. Yet, these sources of influences are not independent. For example, child maltreatment has been shown to be partly inherited, which prompts the question of whether the genetic makeup of a child may become phenotypically expressed into aggression through these experiences. This study examined the association between a polygenic score for aggression (PGSAGG) and developmental trajectories of aggression and its mediation by child maltreatment experiences. As prior studies often overlooked the functions of aggression, we tested if these associations varied according to reactive and proactive aggression 721 participants with genotyped and prospective measures of maltreatment (birth-12 years) were rated for aggression behaviors at up to six occasions by independent teachers (6 to 13 years). The PGSAGG was calculated using a Bayesian estimation method (PGS-CS) according to the most recent GWAS for aggression among children (Ip et al. 2021). PGSAGG predicted a higher risk to belong to high-increasing trajectories of global, reactive, and proactive aggression, as well as to high-decreasing trajectories of global and reactive aggression, in comparison to a low-stable trajectory of aggression. When adjusting for co-occurring reactive and proactive aggression, however, only reactive aggression remained associated with the PGSAGG. Child maltreatment partially mediated the association between the PGSAGG and belonging to high-decreasing global and reactive aggression trajectories (vs low-stable; indirect Bootstrapped estimates:>.20(.09), ps≤03)). These findings shed light on how genetic factors may be phenotypically expressed into reactive, but not proactive aggression, in part through child maltreatment experiences.
Abstract for Presentation 4
CENTRAL INSULIN FUNCTION MODERATES THE IMPACT OF EARLY LIFE ADVERSITY ON GROWTH, BEHAVIOR AND LONG-TERM DISEASE RISK – TRANSLATIONAL STUDIES
Adversities happening early in life (e.g., malnutrition, maternal diseases, family dysfunction), affect brain development and child health but also have an impact on the risk for common adult diseases (e.g., diabetes, cardiovascular disease, depression and substance use disorders). Derangement of insulin function is a common feature in these metabolic and psychiatric disorders, being also highly affected by early life stress. Our lab investigates the role of brain insulin in defining the health/disease patterns in individuals exposed to early adversity. Using advanced functional genomics techniques and relevant animal models, we identify brain region specific gene networks responsive to early life stress and to insulin administration and apply this information in translational models to identify vulnerability to the long-term effects of adversity in humans. In a series of studies, we discovered that insulin related gene-co-expression polygenic scores are able to identify risk for increased impulsivity, addiction and mood disorders, as well as altered eating behavior and increased adiposity in response to early adversity, throughout the life course. Our novel methods demonstrate for the first time that the co-morbidity between metabolic and mental disease is highly influenced by the exposure to early life stress, and that brain insulin function is an important mediator of these effects, with differential findings in men and women. Our results indicate a neuroendocrine sex-dependent modulation of adversity response and programming through the central insulin function, possibly acting on the dopaminergic system involved in behavioral inhibition and decision-making processes.