Early life stress, adolescent brain development and risk for adverse cognitive and psychosocial outcomes

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This project aims to study pre and postnatal childhood factors and examine their association with HPA-functioning, cognition, and mental health during adolescence in the Western Australian Pregnancy Cohort Study (Raine Study). Childhood exposures include not only trajectories of stressful life events, family functioning and mental health status during childhood, but also effects of intrauterine and postnatal growth patterns, and a comprehensive range of psychosocial, familial and environmental factors. It is our objective to characterise functional polymorphisms for genes related to stress regulation and examine their interactions with early life exposures and their neurobiological consequences. We will also test 16 year old Raine subjects for cognitive ability, and in some we will image their brain activity while performing these tests. We anticipate to enhance the already comprehensive phenotypic Raine Study data base with neurobiological information for future neuroscience studies as the Raine cohort matures. We hypothesise that increased and sustained trajectories of early life stress, family dysfunction or poor mental health during childhood will increase the risk of Raine Study adolescents experiencing: (i) - increased stress sensitivity with higher baseline cortisol levels during adolescence; (ii) - increased adolescent stress sensitivity, if they are carriers of specific haplotypes of the glucocorticoid and mineralocorticoid receptor genes.;(iii) - depression during adolescence, if they are homozygous or heterozygous for the short allele of the serotonin transporter (5-HTT) gene; (iv) - poorer cognitive performance and increased atypical non-prefrontal cortex (PFC) brain activity during cognitive testing as measured by fMRI; and (v) -more mental health problems during adolescence.