"Sex and the Suffering Brain”: Linking Sex Hormone Actions with Psychiatric Illness in the Human Brain across the Lifespan

First PhD paper published and second in full swingFor the second PhD project, the PhD candidate assesses whether sex moderates the link between polygenic risk scores for sex-biased disorders and brain aging in middle to older-aged British White adults, pooled both with and without the disorders of interest (Alzheimer’s Disease, Parkinson’s Disease, depression, and schizophrenia).This second PhD project is a follow-up to Study 1, assessing brain health and using the UK Biobank sample of middle- to older-aged adults while extending to both sexes. This study is titled, "Investigating the role of sex on the link between genetic risk for sex-biased disorders and brain age" and has been preregistered (https://osf.io/a8pt2/). Preregistration reflects commitment for transparency and the reduction of publication bias in scientific research. Analyses for this study are in progress, and the candidate is writing up the paper. Previous research shows that there are sex differences in several neurodegenerative and mental disorders which are known to impact brain health. The interaction between sex and genetics might play an important role in disease-related sex differences due to the modulating role of sex on gene expression. Therefore, we were interested in assessing whether there are sex differences in the link between genetic risk for sex-biased disorders and brain health. Disorders of interest include Alzheimer’s disease, Parkinson’s disease, major depressive disorder, and schizophrenia. The proxy measure of brain heath is brain age, derived from white matter and grey matter brain scans. Genetic risk was measured using polygenic risk scores, which are combined scores that estimate genetic vulnerability to a particular trait or disease. Polygenic risk scores are calculated based on genome-wide association studies, which identify the genes associated with the specific trait or disease of interest. However, these genome-wide association studies often remove the effects of sex. As such, critical information may be missing when using combined-sex polygenic risk scores. In this study we aim to ascertain whether sex moderates the link between polygenic risk and brain aging by comparing polygenic risk scores from a male-only sample, female-only sample, and combined samples. Unraveling the interplay between genetic predispositions and sex in brain aging may help uncover mechanisms driving sex-specific vulnerabilities, paving the way for more precise and effective interventions and treatments for these disorders. In 2024, the candidate got their first PhD paper published and additionally co-authored two empirical papers (1) titled, "Parental status and markers of brain and cellular age: A 3D convolutional network and classification study", which was published in Psychoneuroendocrinology; and (2) titled, "No Causal Links Between Lifetime Estradiol Exposure and Female’s Brain and Mental Health – A Mendelian Randomization Study", which is currently under review. Further, the candidate presented their research at the following conferences: Organization for the Study of Sex Differences (OSSD 2024, Bergen, Norway; poster), and Psychologie und Gehirn (PuG 2024, Hamburg, Germany; oral presentation). The presentation at PuG was part of the symposium, "The Brain on Sex Hormones: Uncovering the Interplay between Affect and Brain Dynamics", which they were invited to partake in. Further, the candidate participated in the Lorentz workshop, “Hormonal fluctuations across the female lifespan: Fostering mental health and wellbeing through all ages” in Leiden, Netherlands. During the workshop, the candidate was involved in launching an interdisciplinary network, the Female Lifespan Association for Mental Health and Neuroendocrinology (FLAME).