Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis : the CARTA consortium

Peer reviewe

Stress Systems and Brain Maturation During Adolescence

Adolescence is a transitional period that involves a number of biological (including sexual maturation) and social changes (e.g., conflicts with peers and adults) that may contribute to brain maturation. Studying the factors that influence changes in the adolescent brain can help us understand brain-behaviour relationships. In this thesis, I focused on how the hypothalamic pituitary adrenal (HPA) axis (i.e., the “stress system”) influences brain maturation (namely, pituitary volume and cortical thickness) during adolescence. I used novel techniques to examine the relationship between HPA axis regulation and activity on brain development during adolescence, as well as how the hypothalamic pituitary gonadal (HPG) axis interacts with the HPA axis in the context of brain development during adolescence. I examined these relationships in a community sample of adolescents (n = 1019, ages 12-18) from the Saguenay Youth Study. In Chapter 2, I validated a segmentation algorithm that estimates the volume of the pituitary gland. Using this segmentation algorithm, I found that age, puberty status, testosterone, and estradiol were positively associated with pituitary volumes in adolescents. In Chapter 3, I calculated a polygenic score based on a panel of genetic variants that were related to the activation of the glucocorticoid receptor (GR) for each participant. With the GR-related polygenic scores, I found that it was positively associated with cortisol levels and pituitary volumes in adolescents. In Chapter 4, I used the expression profiles of genes from the Human Brain Atlas to examine its relationship with age-related cortical thinning across the brain in adolescents. I found a positive relationship between inter-regional variations of NR3C1 and AR mRNA expression and age-related cortical thinning across the brain. In this thesis, I combined the field of genetics, endocrinology, and developmental neuroscience to understand the stress-system and brain maturation during adolescence.Ph.D