Venus and Mars: The Importance of Sex In Late-Life Neuropsychiatric Disorders

Abstract

Sex has increasingly become recognized as an important biological variable in brain disorders. Differences in the risk for both cognitive and emotional disorders by sex and gender are an increasing area of investigation. While women are at higher risk for depression and Alzheimer's disease, the causes of these differences are poorly understood and the implications for therapy not exploited in a systematic way. Advances in clinical and translational neuroscience have begun to reveal potential reasons for these sex differences. Differences in how men and women process emotional information and react to psychological and psychosocial stress as well as the unique hormone environment of women versus men have identified potential causative factors in the preponderance of mood disorders in women. New advances in brain imaging and analysis have revealed novel sex-related differences in structural network connectivity that affects the spread of abnormal proteins, which may help to explain sex-related differences in neurodegenerative disease. Hormonal changes that occur at menopause and beyond may have significant implications for how neurotransmitter system activity changes with normal and pathologic aging and may help to explain why women may be at higher risk for developing Alzheimer's disease. This session will explore advances in our understanding of sex differences in late life neuropsychiatric disorders including depression and neurodegenerative disease. For example, research has identified specific circuits in the brain that are sensitive to sex hormones and are involved in the processing of negative emotional information and in modulating response to psychological stress. These circuits react differentially to the presence of sex hormones and change following menopause and aging. These results may help explain sex differences in mood disorders and changes in sex ratios with normal aging. New research has identified sex-related differences in the spread of tau protein in the brains of patients with normal aging, with women showing more advanced spread and greater structural network connectivity. Whether this sex difference extends to early syndromes such as subjective cognitive decline is under investigation. Women may differ from men in the earliest expression of self-perceived cognitive symptoms due to changes at menopause. The role of gonadal steroids and other individual difference factors like lifetime hormone exposure as well mood and lifetime stress have the potential to modulate these relationships. Discussion will center on how this research may point the way towards sex-specific treatments, prevention strategies, and specific therapies.