Étiologie des différences individuelles liées à la sécrétion cortisolaire à la petite enfance : une étude des facteurs génétiques et environnementaux

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2008-2009L'objectif de cette thèse de doctorat consiste à étudier l'étiologie génétique et environnementale de la sécrétion cortisolaire à la petite enfance, une période du développement caractérisée par une forte plasticité de certaines structures cérébrales. Une attention particulière est accordée à l'investigation des variations des contributions génétiques et environnementales en fonction de l'adversité familiale, indice d'une possible interaction entre les gènes et l'environnement. L'adversité familiale renvoie à une mesure composite de 7 facteurs périnataux et postnaux ayant été liés à la sécrétion cortisolaire (l'exposition prénatale à la cigarette, le faible poids à la naissance, le faible revenu familial, pas de diplôme d'études secondaires, mère monoparentale, le jeune âge de la mère et les comportements maternels hostiles ou réactifs envers les jumeaux). Considérant que les mesures cortisolaires ont été effectuées dans des contextes différents (prélèvements salivaires réalisés à deux temps au cours de la journée vs une réponse à un stress de nouveauté sociale) et à des âges distincts (6 vs 19 mois), la poursuite de cet objectif s'effectue séparément pour ces mesures. Dans un premier temps (article 1; mesure réactive à un contexte de nouveauté sociale à 19 mois), les résultats indiquent une variation des contributions génétiques et environnementales en fonction de l'adversité familiale, prenant la forme d'un effet organisationnel de l'adversité environnementale. Cet effet se traduit par une contribution réduite des facteurs génétiques combinée à une plus forte contribution de l'environnement partagé en contexte d'adversité familiale comparativement à une contribution génétique modérée du cortisol réactif en absence d'adversité familiale. Dans un deuxième temps (article 2; mesures diurnes à 6 mois), les résultats indiquent une variation des contributions génétiques et environnementales de la sécrétion cortisolaire matinale en fonction de l'adversité familiale. Cette variation prend cette fois la forme d'une plus forte héritabilité en présence d'adversité familiale alors que seuls les facteurs environnementaux uniques entrent en jeu en l'absence de ce contexte de vie adverse. Aucune variation des contributions génétiques et environnementales n'est notée sur la sécrétion cortisolaire mesurée au réveil en fonction de l'adversité familiale. Pour cette mesure, seuls les facteurs génétiques expliquent la ressemblance entre les jumeaux d'une même paire

Polygenic risk for aggressive behavior from late childhood through early adulthood

Twin studies suggest a substantial role for genes in explaining individual differences in aggressive behavior across development. It is unclear, however, how directly measured genetic risk is associated with aggressive behavior at different moments across adolescence and how genes might distinguish developmental trajectories of aggressive behavior. Here, a polygenic risk score derived from the EAGLE-Consortium genome-wide association study of aggressive behavior in children was tested as predictor of latent growth classes derived from those measures in an adolescent population (n = 2229, of which n = 1246 with genetic information) and a high-risk sample (n = 543, of which n = 335 with genetic information). In the population sample, the polygenic risk score explained variation in parent-reported aggressive behavior at all ages and distinguished between stable low aggressive behavior and moderate and high-decreasing trajectories based on parent-report. In contrast, the polygenic risk score was not associated with self- and teacher-reported aggressive behavior, and no associations were found in the high-risk sample. This pattern of results suggests that methodological choices made in genome-wide association studies impact the predictive strength of polygenic risk scores, not just with respect to power but likely also in terms of generalizability and specificity.</p

Association of childhood bullying victimisation with suicide deaths: findings from a 50-year nationwide cohort study

BACKGROUND: Bullying victimisation has been associated with increased risk of suicide ideation and attempt throughout the lifespan, but no study has yet examined whether it translates to a greater risk of death by suicide. We aimed to determine the association of bullying victimisation with suicide mortality. METHODS: Participants were drawn from the 1958 British birth cohort, a prospective follow-up of all births in 1 week in Britain in 1958. We conducted logistic regressions on 14 946 participants whose mothers reported bullying victimisation at 7 and 11 years with linked information on suicide deaths through the National Health Service Central Register. RESULTS: Fifty-five participants (48 males) had died by suicide between the age 18 and 52 years. Bullying victimisation was associated with suicide mortality; a one standard deviation increases in bullying victimisation linked to an increased odds for suicide mortality [odds ratio (OR) 1.29; 1.02-1.64] during adulthood. The OR attenuated by 11% after adjustment for individual (e.g. behavioural and emotional problems) and familial characteristics (e.g. adverse childhood experiences, 1.18; 0.92-1.51). Analysis of bullying victimisation frequency categories yields similar results: compared with individuals who had not been bullied, those who had been frequently bullied had an increased odds for suicide mortality (OR 1.89; 0.99-3.62). CONCLUSION: Our study suggests that individuals who have been frequently bullied have a small increased risk of dying by suicide, when no other risk factors is considered. Suicide prevention might start in childhood, with bullying included in a range of inter-correlated vulnerabilities encompassing behavioural and emotional difficulties and adverse experiences within the family

Environmental influence of problematic social relationships on adolescents' daily cortisol secretion : a monozygotic twin-difference study

BACKGROUND: This study investigated the potential environmental effects of peer victimization and the quality of relationships with parents and friends on diurnal cortisol secretion in mid-adolescence. METHOD: This study used the monozygotic (MZ) twin-difference design to control for genetic effects and thus estimate the unique environmental influences on diurnal cortisol. Participants were 136 MZ twin pairs (74 female pairs) for whom cortisol was assessed four times per day over four collection days grouped in a 2-week period in grade 8 (mean age = 14.07 years). Participants also provided self-reports of peer victimization from grade 4 to grade 8 and of the relationship quality with the mother, father and best friend in grade 8. RESULTS: The expected pattern of diurnal cortisol secretion was observed, with high levels at awakening followed by an increase 30 min later and a progressive decrease subsequently. Controlling for a host of confounders, only within-twin pair differences in peer victimization and a problematic relationship with the mother were significantly linked to twin differences in diurnal cortisol secretion. Specifically, whereas a more problematic mother-child relationship was associated with morning cortisol secretion, peer victimization was linked to cortisol secretion later in the day (diurnal slope). CONCLUSIONS: Controlling for genetic influences and other confounders, stressful relationships with peers and the mother exert unique and time-specific environmental influences on the pattern of diurnal cortisol secretion in mid-adolescence

Does cortisol moderate the environmental association between peer victimization and depression symptoms? a genetically informed twin study

Many youths who are victimized by peers suffer from depression symptoms. However, not all bullying victims become depressed and individuals’ biological sensitivity may play an important moderating role in this regard. In line with this notion, peer victimization has been associated with increased depressive symptoms in youth with higher basal cortisol secretion. It is unclear, however, whether this moderating effect of cortisol really concerns the environmental effect of peer victimization on depression. Indeed, genetic factors can also influence individuals’ environmental experiences, including peer victimization, and part of these genetic factors may be those associated with depression. Using a genetically informed design based on 159 monozygotic and 120 dizygotic twin pairs (52% girls) assessed at age 14 years, this study examined whether cortisol secretion moderates the environmental or the genetic association between peer victimization and depression symptoms. Salivary cortisol at awakening was obtained with buccal swabs during four school week days. Peer victimization and depression were assessed via self-reports. Cholesky modeling revealed that peer victimization was associated with depression symptoms via both genetic and environmental pathways. Moreover, the environmental association between peer victimization and depression symptoms steadily increased with increasing levels of morning cortisol. The genetic association between peer victimization and depression symptoms also varied, albeit less, as a function of individuals’ cortisol secretion. These findings support the hypothesis that peer victimization increases internalizing psychopathology mainly in youth with heightened biological reactivity to environmental conditions

Evidence of a unique and common genetic etiology between the CAR and the remaining part of the diurnal cycle : a study of 14 year-old twins

Introduction By and large, studies have reported moderate contributions of genetic factors to cortisol secreted in the early morning and even smaller estimates later in the day. In contrast, the cortisol awakening response (CAR) has shown much stronger heritability estimates, which prompted the hypothesis that the etiology of cortisol secretion may vary according to the time of day. A direct test of this possibility has, however, not yet been performed. Objective To describe the specific and common etiology of the CAR, awakening level and cortisol change from morning to evening in an age-homogenous sample of twin adolescents. Methods A total of 592 participants of the Québec Newborn Twin Study, a population-based 1995–1998 cohort of families with twins in Canada, have collected saliva at awakening, 30 min later, at the end of afternoon and in the evening over four collection days. Results Multivariate Cholesky models showed both specific and common sources of variance between the CAR, awakening and cortisol diurnal change. The CAR had the strongest heritability estimates, which, for the most part, did not overlap with the other indicators. Conversely, similar magnitudes of genetic and environmental contributions were detected at awakening and for diurnal change, which partially overlapped. Conclusion Our study unraveled differences between the latent etiologies of the CAR and the rest of the diurnal cycle, which may contribute to identify regulatory genes and environments and detangle how these indicators each relate to physical and mental health

Intimate partner violence and new-onset depression : a longitudinal study of women's childhood and adult histories of abuse

Background—Studies indicate that women victims of intimate partner violence are at increased risk for poor mental health. This research disentangled the effect of partner violence on new-onset depression and psychosis spectrum symptoms from effects of child maltreatment and other confounding factors, including substance abuse and antisocial personality. Methods—Participants were 1,052 mothers involved in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative cohort of families followed prospectively. To test the directionality of associations between partner violence and depression, only women without a history of depression at the beginning of the study were considered (n = 978). Partner violence and mental health were assessed during face-to-face interviews with women across three time points. Results—Four of 10 women reported being the victim of violence from their partner in a 10-year period. They represent 33% of our cohort and they account for 51% of new-onset depression. These women had a twofold increase in their risk of suffering from new-onset depression once the effect of childhood maltreatment, socioeconomic deprivation, antisocial personality, and young motherhood were controlled. Women who were abused both in childhood and adulthood were four to seven times more likely to suffer from depression than never-abused women. We observed similar associations with psychosis spectrum symptoms. Conclusions—Women victims of partner violence account for more than their share of depression. Findings strengthen existing evidence that partner violence independently contributes to women’s poor mental health. Psychological difficulties among a considerable number of women could be reduced by stopping partner violence

The Quebec newborn twin study at 21

This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child’s environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene–environment transactions in development

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

Gouin, J.-P., Zhou, Q. Q., Booij, L., Boivin, M., Côté, S. M., Hébert, M., Ouellet-Morin, I., Szyf, M., Tremblay, R. E., Turecki, G. & Vitaro, F. (2017) Associations among oxytocin receptor gene (OXTR) DNA methylation in adulthood, exposure to early life adversity, and childhood trajectories of anxiousness. Scientific Reports, 7(1), 1-14 (7446).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