Sex, hormones, and genotype interact to influence psychiatric disease, treatment, and behavioral research

Abstract

Sex differences exist in the vulnerability, incidence, manifestation, and treatment of numerous neurological and psychiatric diseases. Despite this observation prominent in the literature, little consideration has been given to possible sex differences in outcome in both preclinical and clinical research. This Mini-Review highlights evidence supporting why studying sex differences matter for advances in brain health as well as improving treatment for neurological and psychiatric disease. Additionally, we discuss some statistical and methodological considerations in evaluating sex differences as well as how differences in the physiology of the sexes can contribute to sex difference in disease incidence and manifestation. Furthermore, we review literature demonstrating that the reproductive experience in the female can render the female brain differentially vulnerable to disease across age. Finally, we discuss how genes interact with sex to influence disease risk and treatment and argue that sex must be considered in precision medicine. Together the evidence reviewed here supports the inclusion of males and females at all levels of neuroscience research. V C 2016 Wiley Periodicals, Inc.

Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies

“…Sex differences in psychiatric disorders are well-recognized yet poorly understood clinical phenomena [1][2][3]. Neurodevelopmental disorders, including intellectual disability (ID), autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD), are more prevalent in males compared to females and have different clinical manifestations in males and in females [4][5][6][7][8].…”

Sex differences in the adult human brain: Evidence from 5,216 UK Biobank participants

“…Sex differences in human brain structure and function are of substantial scientific interest because of sex-differential susceptibility to psychiatric disorders [1,2,3] and because of the potential to explain sex differences in psychological traits [4]. Males are known to have larger brain volumes, though the patterns of differences across brain subregions have typically only been examined in small, inconsistent studies [5].…”

“…We report evidence on the pattern of sex differences in brain volume, surface area, cortical thickness, white matter microstructure, and functional connectivity between adult males and females in the range between middle-and older-age. As has previously been argued [61], providing a clear characterisation of neurobiological sex differences is a step towards understanding patterns of differential susceptibility to neurodevelopmental disorders such as autism spectrum disorder [1], a variety of psychiatric conditions [2], and neurodegenerative disorders such as Alzheimer's Disease [13,62]. Data on many thousands of further MRI scans (to a maximum sample of 100,000 with MRI data) will be available from UK Biobank in the coming months and years, in addition to more complex cognitive testing batteries and genotypic data.…”

Impact of EMBODY Experiencing Dementia through New Media Exhibit: Engaging nursing students and the public about dementia through arts-based knowledge translation methods

“…[9,10] There are prominent differences in the BPSD experienced according to sex; women are more likely to experience depression, anxiety and agitation then men with Alzheimer's disease. [11] Men were found to be more likely to experience aggressiveness and diurnal rhythm issues than women. [12] These findings necessitate the need for awareness and training among healthcare providers and students regarding the appropriate management of sexrelated BPSD.…”