Title: Female (mental) health, genetics, and the role of sex hormones; research gaps and novel approaches
Abstract: A striking observation is that men and women experience different mental health disorders at varying rates. For example, mood disorders like depression are nearly twice as prevalent in women as they are in men. In contrast, schizophrenia seems to occur later in women than men, and also with slightly different symptomology. One potential explanation for these sex differences might be that sex hormones play a role, which vary significantly between men and women. Thus, a better understanding what influences levels of these hormones and how this links to disease may help us identify, diagnose, and treat these disorders better. However, at the moment, we know relatively little about genetic regulation of reproductive hormones, individual differences therein, and how this (genetically) relates to the risk of developing different mood and psychiatric outcomes.
In this seminar, dr. Margot van de Weijer will reflect on this research gap in general, and present a novel and ongoing project in collaboration with prof. Michel Nivard on modelling the menstrual cycle in a new genome-wide association study (GWAS) for oestradiol. In men, oestradiol levels are relatively stable, especially over short periods of time such as a month. In women, however, oestradiol levels fluctuate significantly (and predictably) over the menstrual cycle, peaking just before ovulation and dropping steeply after. Therefore, any between-subject investigation of oestradiol concentrations could be significantly confounded (and underpowered) if not taking into account timing of the sampling relative to the participant’s menstrual cycle phase. Current GWA efforts have not explicitly modelled oestradiol concentrations as a function of menstrual cycle phase, potentially explaining the paucity of evidence in this area. We aim to tackle this problem by 1) performing GWASs with exceedingly strict sample selection based on sex, menopause status, and other confounders such as contraceptive use and hormone-replacement therapy (HRC), and 2) taking into account the cycle-dependent intra-individual variation in oestradiol concentrations.
Biography:
Margot van de Weijer is an assistant professor at the department of psychiatry at the Amsterdam University Medical Centers, the Netherlands. She completed her PhD in behavior genetics at VU University (Amsterdam) in 2023 and subsequently joined the genetic epidemiology research team at the Amsterdam UMC. Her research currently focuses on two domains; 1) gene-environment interplay and causal pathways between substance use and mental health disorders, and 2) more recently, the role of sex hormones in female mental health and mental health sex differences. With an interdisciplinary background in psychology, genetics, neuroscience, and philosophy, she integrates methods and theories from these different fields in order to answer complex mental health questions.