Symposium
Estradiol is the predominant sex steroid in females and has been implicated in the development of depression and Alzheimer’s disease – two disorders that disproportionately affect females compared to males. Despite well-established sex differences in these brain disorders, there has been a limited focus on the effects of endocrine aging on brain health and mental health in females. If studied at all, research commonly relies on small datasets, emphasizing the need for big data studies and concerted consortia efforts to increase power, reproducibility, and generalizability of female brain health studies. In my talk, I will spotlight female brain health by informing on the role of estradiol and factors related to estradiol exposure on the aging female brain and risk for depression and Alzheimer’s disease. First, I will present our work on studying these associations using large-scale population-based datasets and machine learning tools within a conventional observational framework relying on cross-sectional data. Second, I will move from an observational to a causal framework by showcasing our work using Mendelian randomization (MR), a computational method which uses genetic variants to test for causal exposure-outcome relationships in a large female-only sample. Lastly, I will conclude the talk by introducing our recently launched ENIGMA Neuroendocrinology Working Group which aims at pooling datasets globally to explore the effects of hormonal transition periods on female brain health. In summary, by using large-scale, female-only samples, and state-of-the-art methods in observational as well as causal frameworks, our research provides a unique contribution to our current understanding of potential effects of sex steroids on female brain and mental health.
Funding: The work is supported by the South-Eastern Norway Regional Health Authority (PI CB: 2023037, 2022103) and the European Research Council (PI CB: 101163765).
Relevant recent publications:
- Barth, C., Galea, L. A., Jacobs, E. G., Lee, B. H., Westlye, L. T., & de Lange, A. M. G. (2024). Menopausal hormone therapy and the female brain: leveraging neuroimaging and prescription registry data from the UK Biobank cohort. eLife 13:RP99538.
- Heller, C., Barth, C., Silk, T. J., Vijayakumar, N., Carmona, S., Martínez-García, M., ... & Petersen, N. (2024). The ENIGMA-Neuroendocrinology working group to bridge gaps in female mental health research. Nature Mental Health, 2(4), 348-350.
- Barth, C., Crestol, A., de Lange, A. M. G., & Galea, L. A. (2023). Sex steroids and the female brain across the lifespan: insights into risk of depression and Alzheimer's disease. The Lancet Diabetes & Endocrinology.
- Oppenheimer, H., van der Meer, D., Schindler, L., Crestol, A., Westlye, L. T., de Lange, A. M. G., & Barth, C. No Causal Links Between Lifetime Estradiol Exposure and Female’s Brain and Mental Health–A Mendelian Randomization Study. preprint