Impacts of stress and sex hormones on the adolescent brain – ADOSTRESS

Adolescence is considered as a sensitive period for social stress. With the onset of puberty, stress-reactivity rises, as does the risk for development of psychopathology, while recovery from social stress is compromised. Together, these suggest a link between stress physiology and sexual maturation during adolescence. So far, the neuroendocrine responses to social stress and their consequences for the developing adolescent brain have been only inadequately characterized. We will consider potential developmental differences between hypothalamus-pituitary-adrenal axis (HPA) and the hypothalamus-pituitary-gonadal axis (HPG) in the adolescent stress response, as well as the potential reversal of the role of a subset of adrenal hormones in early adolescent stress reactivity. In addition, we will also consider differences in the evolutionary-based adaptation of the male and female neuroendocrine stress response. Combining behavioral, neuroendocrine and model-based functional magnetic resonance imaging (fMRI) approaches, this project will determine how acute social stress interacts with gonadal hormones and influences brain activity in early and late adolescent boys and girls, and how hormonal contraception modulates stress-reactivity in late adolescent girls.
The objectives of this project are to determine:
a. the association of gonadal and adrenal hormones with inter-individual differences in stress reactivity that manifest with the onset of puberty in early vs. late adolescents;
b. the influence of stress on learning social hierarchy and non-social reinforcement learning during adolescence;
c. the causal role of hormonal contraception on the brain systems implicated in the different aspects of learning compared to naturally fluctuating gonadal hormones in adolescent girls, again in relation to their interaction with the neuroendocrine stress response;
d. the influence of pubertal development (early vs. late adolescence) and of baseline testosterone on stress reactivity of maturing boys and its relation to social and non-social learning as well as brain activation under stress;
e. the influence of inter-individual personality differences such as trait anxiety and dominance on brain activation and the stress response across adolescence.
We will test 300 adolescents with an identical fMRI protocol: 60 early adolescent boys and 60 girls (11-13ys), 60 late adolescent boys (15-18ys), and 120 late adolescent girls (15-18ys), of whom 60 will be receiving hormonal contraception, while another 60 will be in the luteal phase of their menstrual cycle. Participants will first undergo the Trier Social Stress Task (TSST) or a non-stress control intervention. Then, they will perform two fMRI tasks: the first task will assess social dominance learning, as a key aspect of social interactions during adolescence (SDL task) and the second task will test basic reinforcement learning capacity in a non-social setting (RL task).
We will collect one pre and two post stress saliva samples for endocrine analysis. We will track stress-reactivity in salivary cortisol, allopregnanolone, progesterone and testosterone as well as subjective stress perception. We will test whether acute stress influences social learning or RL in general. We will compare our fMRI findings of social hierarchy learning in early vs late adolescence and will also investigate the influences of gonadal and adrenal hormones, trait anxiety and dominance, as well as hormonal contraception on the identified brain system. With this project, we intend to achieve a better understanding of brain maturation during adolescence with a focus on the accompanying neuroendocrine determinants of stress-reactivity and their role in future psychopathology. We expect that the interactions of several gonadal and adrenal hormones with the cortisol stress response are involved in the heightened sensitivity of the adolescent brain for social stressors in the context of competitive social interactions.