Women’s neurology and mental health are defined as the study of neurologic and psychiatric disorders approached through a sex-based lens. This chapter will discuss some of the sex-based differences in neurologic and psychiatric disorders. The specific concerns vary depending on the disorder, where the woman is in her reproductive cycle, and her psychosocial milieu. The neurologic diseases to be reviewed are those with significant sex differences in prevalence, clinical presentation, or management. They include systemic lupus erythematosus (SLE), migraine, epilepsy, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, stroke, and Alzheimer’s disease (AD). The psychiatric disorders to be discussed will include those that are related to, or influenced by, the reproductive events in a woman’s life—including perimenstrual disorders, perinatal disorders, and perimenopausal disorders. We will focus on these periods of increased hormonal variability and discuss the relationship between sex hormones and serotonergic, dopaminergic, GABAergic, and glutamatergic transmission, and other neurobiological factors. While the focus of this chapter is on the sex differences in epidemiology, clinical features, pathophysiology, and treatment of many neurologic and psychiatric disorders, it is important to note that these same disorders are covered in detail in other chapters of this textbook. We direct the reader to the specific chapters, as appropriate, within each of the subtitles below.
AUTOIMMUNE DISEASE AND MULTIPLE SCLEROSIS
An autoimmune disorder occurs when the immune system mounts an attack against the body’s own antigens, via a cell-mediated or autoantibodies-mediated mechanism, causing injury to host tissue. Autoimmune diseases affect approximately 8% of the population, and 78% of those affected are women.1 This increased prevalence in women is likely related to the role of estrogens on both cell- and antibody-mediated immunity. In cell-mediated immunity, androgens and estrogens regulate the Th1 (helper)/Th2 (suppressor) balance. These types of cell-mediated autoimmune diseases are improved when there is a decrease in type 1 cytokines, proinflammatory T cells, or when there is a rise in type 2 cytokines causing a suppression of inflammatory activity (corresponding to increased estrogens, as in pregnancy).2
Multiple sclerosis is an example of a cell-mediated autoimmune disorder in which shifts in cytokine types during pregnancy lead to fetal immunotolerance (the fetus represents a “foreign entity” to the maternal immune system; immunological tolerance during pregnancy protects against a maternal immune response directed at the paternal antigens expressed by the fetus). The result is that relapse rates typically improve during pregnancy with flares in the postpartum period.3 Chapter 27, Multiple Sclerosis, reviews in detail the neuropsychiatric manifestations of this illness. In animal models, females generate more antibodies after vaccination compared to males.4 This may explain why antibody-mediated autoimmune disorders such as SLE, Sjogren’s syndrome, and neuromyelitis optica occur much more frequently in women. SLE will be described as an example of an autoimmune disorder in which there are significant sex differences.
SYSTEMIC LUPUS ERYTHEMATOSUS