Impacts of stress and sex hormones on the adolescent brain

• Applicant: Professorin Dr. Esther Diekhof
• Subject Area: Human Cognitive and Systems Neuroscience
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 491188065

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, which suggests a link between stress physiology and sexual maturation. So far, the neuroendocrine responses to social stress and its consequences on the 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 in 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 in 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 brain activity during social hierarchy and non-social reinforcement learning in adolescents; (c) the role of hormonal contraception in the neuroendocrine stress response of late adolescent girls; and (d) the influence of inter-individual personality differences (trait anxiety and dominance) on brain activation and the stress response across adolescence. We will test 300 adolescents with an identical fMRI protocol (120 early adolescent boys and girls [11-13ys], 60 late adolescent boys and 120 late adolescent girls [15-18ys], of whom 60 will receive hormonal contraception, while the remaining 60 will be in the luteal phase of their menstrual cycle). Participants will undergo the Trier Social Stress Task or a non-stress control intervention and will perform two fMRI tasks: (a) a social dominance learning task, as a key aspect of social interactions during adolescence, and (b) a basic reinforcement learning in a non-social setting. We will collect pre- and post-stress saliva samples to track stress-reactivity in cortisol, allopregnanolone, progesterone and testosterone. With the planned 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 during competitive social interactions.

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partner: Dr. Jean-Claude Dreher