title: Sex in Context: Limitations of Animal Studies for Addressing Human Sex/Gender Neurobehavioral Health Disparities.
abstract: Many brain and behavioral disorders differentially affect men and women. The new National Institutes of Health requirement to include both male and female animals in preclinical studies aims to address such health disparities, but we argue that the mandate is not the best solution to this problem. Sex differences are highly species-specific, tied to the mating system and social ecology of a given species or even strain of animal. In many cases, animals poorly replicate male-female differences in brain-related human diseases. Sex/gender disparities in human health have a strong sociocultural component that is intimately entangled with biological sex and challenging to model in animals. We support research that investigates sex-related variables in hypothesis-driven studies of animal brains and behavior. However, institutional policies that require sex analysis and give it special salience over other sources of biological variance can distort research. We caution that the costly imposition of sex analysis on nearly all animal research entrenches the presumption that human brain and behavioral differences are largely biological in origin and overlooks the potentially more powerful social, psychological, and cultural contributors to male-female neurobehavioral health gaps.
authors.affiliation: Department of Neuroscience, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, and lise.eliot@rosalindfranklin.edu.
authors.forename: Lise
authors.identifier: 0000-0003-0247-2645
authors.initials: L
authors.lastname: Eliot
authors.affiliation: Department of the History of Science, Committee on Degrees in Studies of Women, Gender, and Sexuality, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: Sarah S
authors.identifier: 0000-0002-9462-3051
authors.initials: SS
authors.lastname: Richardson
mesh_terms: D000818:Animals; D035843:Biomedical Research / Q000379:methods*; D001927:Brain Diseases / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000503:physiopathology*; D023421:Models, Animal; D009488:Neurosciences / Q000379:methods; D012727:Sex Characteristics; D012737:Sex Factors; D063507:Sexism; D014481:United States
keywords: NIH; SABV; anxiety and depression; gender; health disparities; pain; sex difference