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Couched in the aims of \u201cprecision medicine,\u201d the vast majority of this research has taken a binary approach, dividing participants according to the M\/F box at intake and asserting that the sex differences found in neuroimaging will lead to important advances for treating neuropsychiatric disorders. However, the actual findings from this 40\u2010year project have not lived up to its promise, in part because of the over\u2010binarization of sex and general ignorance of gender as a complex variable influencing human behavior and brain function. This paper reviews the history of failed claims about male\u2013female brain difference in the modern era, illuminates the deep\u2010pocketed incentives driving such research, and examines the limitations of this binary approach for understanding gender\u2010related behavior and health disparities. It then considers more recent efforts to \u201cbreak the binary\u201d by using measures of \u201cgender\u201d in addition to \u201csex\u201d as an independent variable in brain imaging studies. Given the multidimensional nature of gender\u2014as identity, expression, roles and relations\u2014this is challenging to implement, with initial efforts producing little of substance. Better approaches to addressing male\u2013female disparities in brain health will require focusing on specific behaviors (e.g., anxiety, risk\u2010taking, verbal memory, spatial navigation) and specific components of sex and gender (e.g., body size, hormone levels, gene expression, caregiver role, financial independence, discrimination) when seeking brain\u2010behavior correlates in a diverse population.<\/jats:p>","DOI":"10.1002\/ajhb.70041","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T10:46:47Z","timestamp":1744282007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["\u201cPrecision Medicine\u201d and the Failed Search for Binary Brain Sex Differences to Address Gender Behavioral Health Disparities"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0247-2645","authenticated-orcid":false,"given":"Lise","family":"Eliot","sequence":"first","affiliation":[{"name":"Chicago Medical School, Stanson Toshok Center for Brain Function and Repair Rosalind Franklin University of Medicine &amp; 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