Effects of sex and prenatal alcohol exposure on early childhood gray matter volume and executive function

Abstract

Brain development is a dynamic process, characterized by both progressive and regressive changes in brain structure. Prenatal alcohol exposure (PAE) can have profound, deleterious effects on brain structural development and is associated with behavioural impairments such as difficulties with executive function. Approximately 4% of North American children will receive a diagnosis of fetal alcohol spectrum disorder (FASD), a lifelong developmental disorder caused by PAE. PAE may interact with other factors such as sex to produce varied brain and executive function outcomes. To date, longitudinal studies examining changes in gray matter volume during early childhood are sparse, especially for young children with PAE. Additionally, while relationships between gray matter volume, sex, and executive function have been explored in adolescent and adult populations, the gray matter volume executive function relationship remains unknown for young children both with and without PAE. This thesis addressed the gap in knowledge about early childhood gray matter volume development and it’s relation to sex, PAE, and executive function by 1) characterizing longitudinal development of cortical and subcortical gray matter volume in typically developing young children aged 2-8 years, 2) comparing regional trajectories of gray matter volume in young children with and without PAE, and 3) determining how executive functioning ability relates to gray matter volume development in children with and without PAE. I used T1-weighted magnetic resonance imaging (MRI) collected in a longitudinal sample of children with and without PAE aged 2-8 years. For children without PAE, I found that rates of change in cortical and subcortical gray matter volume were similar for males and females in most (114/116) regions. Next, I showed that young children with PAE have altered gray matter development as compared to unexposed children, and that within the sample of children with PAE rates of developmental change in volume were similar for males and females. Additionally, females with PAE had smaller gray matter volume than the other groups. Lastly, I found that unexposed males and males with PAE had opposite volume-executive function associations; larger volume was associated with better executive function in males with PAE. Unexposed females also showed strong, positive volume-executive function association whereas females with PAE generally showed weaker volume-executive function relationships than unexposed females. The research presented in this dissertation highlights the value of longitudinal neuroimaging data to explore developmental changes in brain anatomy in early childhood. It also illustrates the importance of considering sex in developmental studies, as male and female children may show different brain developmental patterns which might underly different behavioural outcomes. Lastly this dissertation shows that brain differences exist as early as age 2 or 3 years for children with PAE. These findings could be leveraged toward advocating for earlier detection and diagnosis of FASD.