Sex differences are crucial for understanding the brain, yet neuroscience has long favored male models, skewing insights and clinical outcomes. Now, researchers integrate sex as a biological variable in their studies, paving the way for more balanced and inclusive neuroscience research.
1990s: Historically, most of the basic research and clinical studies predominantly focused on male models (humans, animals, and cells). It wasn’t until 1993 that the U.S. Congress passed a law in requiring inclusion of women in National Institutes of Health (NIH)-sponsored clinical trials. However, this policy failed to encourage the same standards in basic research.
Early 2000s: The field was influenced by a long-standing belief: fluctuating hormones of the estrous cycle complicated female studies. However, studies showed that female mice and rats were not more variable in non-neurological and neurological outcomes than male animals.1-3 This led to a call for female animal inclusion scientific experiments, as neuroscience had a stark sex gap due to male-focused studies.4
Late 2010s: In 2016, the NIH enforced the “Sex as a Biological Variable” (SABV) policy, requiring sex to be factored into research designs, analyses, and reporting in biomedical research when applicable. More researchers incorporated female animals, rodents and nonhuman primates, and cell lines, such as induced pluripotent stem cells, to better understand sex differences in neurological disease.5,6
2016–Present: Since SABV, the number of neuroscience studies including both sexes significantly increased.7,8 Now, researchers are reframing their analyses of female data to better understand biological differences and shape developing therapeutics.
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- Prendergast BJ, et al. Female mice liberated for inclusion in neuroscience and biomedical research. Neurosci Biobehav Rev. 2014;40:1-5.
- Becker JB, et al. Female rats are not more variable than male rats: a meta-analysis of neuroscience studies. Biol Sex Differ. 2016;7:34.
- Levy DR, et al. Mouse spontaneous behavior reflects individual variation rather than estrous state. Curr Biol. 2023;33(7):1358-1364.e4.
- Beery AK, Zucker I. Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev. 2011;35(3):565-572.
- Rothwell E, et al. Sex differences in marmoset neurocognitive aging, a nonhuman primate model for brain aging and age?related neurodegenerative diseases. Alzheimer’s & dementia. 2023;19(S18).
- Dolmetsch R, Geschwind DH. The human brain in a dish: the promise of iPSC-derived neurons. Cell. 2011;145(6)831-834.
- Woitowich NC, et al. A 10-year follow-up study of sex inclusion in the biological sciences. Elife. 2020;9:e56344.
- Rechlin RK, et al. An analysis of neuroscience and psychiatry papers published from 2009 and 2019 outlines opportunities for increasing discovery of sex differences. Nature communications. 2022;13(1): 2137.
