Associations between estradiol, brain structure and function, and extinction recall in adolescents

Background: Adolescence is a life stage where anxiety and depressive (internalising) disorders emerge. Internalising disorders are twice as prevalent in females as males, a pattern apparent in adolescence. This sex disparity may be explained by pubertal and neurodevelopmental factors, as dramatic hormonal changes and dramatic brain changes occur during adolescence. Individual differences in pubertal hormones may interact with neurodevelopment to impact mental health. The sex steroid hormone estradiol is key in puberty, however few studies have examined associations between estradiol, neurodevelopment, and internalising symptoms, particularly in adolescents. In fact, estradiol may influence neural networks important for emotional processing and regulation, where alterations in these neural networks may underlie emotion dysregulation underlying internalising disorders. Aims: This thesis aims to investigate associations between estradiol variability (secondarily, average estradiol) and brain structure in female adolescents, as well as whether brain structure mediates longitudinal associations between estradiol variability and internalising symptoms. Further, we aim to investigate associations between estradiol variability (secondarily, average estradiol and estradiol level) and brain activation during emotion processing, as well as whether brain function mediates longitudinal associations between estradiol variability and internalising symptoms. Finally, the current thesis aims to explore associations between brain structure, fear extinction recall and trait and state anxiety symptoms, as well as moderating effects of age and sex, in a pilot study of adults and adolescents. Method: Study 1 and Study 2 of this thesis utilised the same sample of 44 female participants measured at age ~12 years (baseline) and age 13 years (follow-up). At baseline adolescents completed self-report questionnaires measuring anxiety (Spence Children’s Anxiety Scale) and depressive (Children’s