Menopause and Severe Mental Illness: Risk Factors for New Onset Disorders and the Role of Hormone Therapy in Women with Pre-Existing Mental Health Conditions Despite menopause affecting roughly half the world’s population, there is a striking lack of research on the role of menopause in the development and clinical course of severe mental illness (SMI). While prior studies link menopause to mood and anxiety symptoms, far less is known about its impact on SMI (including schizophrenia spectrum disorders (SSD) and bipolar disorder (BP)). Menopause as a vulnerable period for new onset SMI has been widely suggested, but empirical evidence is lacking. This project aims to examine risk and protective factors for women who develop SMI during the menopause time frame and the course of illness for women with SMI during the menopause transition. By using large scale registry data this research will yield novel and clinically valuable insights into both biological and systemic health factors affecting women during midlife. The objectives of this project are threefold: 1) to determine whether menopause is associated with increased risk of developing new onset SMI; 2) to identify disparities in access to menopausal hormone treatment (MHT) for those already living with SMI; 3) and to evaluate how MHT affects adverse outcomes in midlife women with SMI. Importantly, this research will address knowledge gaps affecting mid- to late-life women’s mental health during the menopause transition – an underfunded and historically overlooked area of study. Aim 1: 1a) To identify the incidence of new onset SMI (SSD and BP) in women of menopausal age; 1b) To evaluate the association of new onset SMI with menopause-related risk factors (e.g. symptomatic menopause, MHT) and with risk factors in other domains (sociodemographics, life stressors, medical- and mental health risk factors). Aim 2: 2a) To compare dispensation rates of MHT among women with and without SMI, in both Swedish and U.S. healthcare systems. 2b) To investigate factors (health care utilization, sociodemographics) that influence disparities in MHT for women with and without SMI. Aim 3: To evaluate the impact of MHT on psychiatric hospitalization in women with SMI. The cohort consists of over 2 million women, and data used is taken from nationwide Swedish Registers, with information about health care use, diagnoses, medications, demographics, disability and immigration. BIANCA resources will primarily be needed for aim 2 and 3, where both Generalized Estimating Equations and Target Trial Emulations are planned.