Sex differences exist in many neurological and psychiatric diseases, but these have not always been addressed adequately in research. In order to address this, it is necessary to consider how sex is incorporated into the design (e.g. using a balanced design) and into the analyses (e.g. using sex as a covariate) in the published literature. We surveyed papers published in 2009 and 2019 across six journals in neuroscience and psychiatry. In this sample, we find a 30% increase in the percentage of papers reporting studies that included both sexes in 2019 compared with 2009. Despite this increase, in 2019 only 19% of papers in the sample reported using an optimal design for discovery of possible sex differences, and only 5% of the papers reported studies that analysed sex as a discovery variable. We conclude that progress to date has not been sufficient to address the importance of sex differences in research for discovery and therapeutic potential for neurological and psychiatric disease.

Background Sex and gender impacts health outcomes and disease risk throughout life. The health of women and members of the Two-Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning (2S/LGBTQ +) community is often compromised as they experience delays in diagnosis. Distinct knowledge gaps in the health of these populations have prompted funding agencies to mandate incorporation of sex and gender into research. Sex- and gender-informed research perspectives and methodology increases rigor, promotes discovery, and expands the relevance of health research. Thus, the Canadian Institutes of Health Research (CIHR) implemented a sex and gender-based analysis (SGBA) framework recommending the inclusion of SGBA in project proposals in 2010 and then mandating the incorporation of SGBA into grant proposals in 2019. To examine whether this mandate resulted in increased mention of sex or gender in funded research abstracts, we searched the publicly available database of grant abstracts funded by CIHR to analyze the percentage of abstracts that mentioned sex or gender of the population to be studied in the funded research. To better understand broader health equity issues we also examined whether the funded grant abstracts mentioned either female-specific health research or research within the 2S/LGBTQ + community. Results We categorized a total of 8,964 Project and Operating grant abstracts awarded from 2009 to 2020 based on their study of female-specific or a 2S/LGBTQ + populations or their mention of sex or gender. Overall, under 3% of grant abstracts funded by CIHR explicitly mentioned sex and/or gender, as 1.94% of grant abstracts mentioned sex, and 0.66% mentioned gender. As one of the goals of SGBA is to inform on health equity and understudied populations with respect to SGBA, we also found that 5.92% of grant abstracts mentioned female-specific outcomes, and 0.35% of grant abstracts focused on the 2S/LGBTQ + community. Conclusions Although there was an increased number of funded grants with abstracts that mentioned sex and 2S/LGBTQ + health across time, these increases were less than 2% between 2009 and 2020. The percentage of funded grants with abstracts mentioning female-specific health or gender differences did not change significantly over time. The percentage of funding dollars allocated to grants in which the abstracts mentioned sex or gender also did not change substantially from 2009 to 2020, with grant abstracts mentioning sex or female-specific research increasing by 1.26% and 3.47%, respectively, funding allocated to research mentioning gender decreasing by 0.49% and no change for 2S/LGBTQ +-specific health. Our findings suggest more work needs to be done to ensure the public can evaluate what populations will be examined with the funded research with respect to sex and gender to advance awareness and health equity in research.

Females show greater benefits of exercise on cognition in both humans and rodents, which may be related to brain-derived neurotropic factor (BDNF). A single nucleotide polymorphism (SNP), the Val66Met polymorphism, within the human BDNF gene, causes impaired activity-dependent secretion of neuronal BDNF and impairments to some forms of memory. We evaluated whether sex and BDNF genotype (Val66Met polymorphism (Met/Met) versus Wild Type (Val/Val)) influenced the ability of voluntary running to increase neurogenesis and cognition in mice. C57BL/6J (13 months) mice were randomly assigned to either a control or an aerobic training (AT) group (running disk access). Mice were trained on the visual discrimination and reversal paradigm in a touch screen-based technology to evaluate cognitive flexibility. BDNF Val/Val mice outperformed BDNF Met/Met mice on both cognitive tasks. Female BDNF Val/Val mice showed greater cognitive flexibility compared to male mice regardless of AT. Despite running less than BDNF Val/Val mice, AT improved both cognitive tasks in BDNF Met/Met mice. AT increased neurogenesis in the ventral hippocampus of BDNF Val/Val mice of both sexes and increased the proportion of mature type 3 doublecortin-expressing cells in the dorsal hippocampus of female mice only. Our results indicate AT results in improved cognitive performance in BDNF Met/Met mice and increased hippocampal neurogenesis in BDNF Val/Val mice in middle age. Furthermore, middle-aged female mice may benefit more from AT than males in terms of neuroplasticity, an effect that was influenced by the BDNF Val66Met polymorphism.

Sex and gender impacts health outcomes and disease risk throughout life. Women and Two-Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning, Intersex, and Asexual (2S/LGBTQIA+) health is often compromised as they experience delays in diagnosis. Distinct knowledge gaps in the health of these populations has prompted funding agencies to mandate incorporation of sex and gender into reearch. Sex- and gender-informed research perspectives and methodology increases rigor, promotes discovery, and expands the relevance of health research. The Canadian Institutes of Health Research (CIHR) implemented a Sex and Gender-based Analysis (SGBA) framework reccommending the inclusion of SGBA in project proposals in 2010 and in 2019, CIHR mandated the incorporation of SGBA into grant proposals. To examine whether these mandates resulted in increased SGBA uptake in research proposals, we searched the publicly available database of proposals funded by CIHR to analyze the amount of research that focused on sex and gender differences in health, as well as the 2S/LGBTQIA+ community. We categorized a total of 8,964 Project and Operating grant abstracts awarded from 2009-2020. Overall, under 10% of research funded by CIHR explicitly examined SGBA, with 1.94% of grants examining sex differences, 0.66% examining gender differences, 5.92% investigating female-specific outcomes, and 0.35% focusing on the 2S/LGBTQIA+ community. Although there was an increased number of grants funded for sex and 2S/LGBTQIA+ health across time, these increases were less than 2% between 2009 to 2020. The percentage of grants investigating female-specific health or gender differences did not change significantly. The percentage of funding dollars allocated to proposals analyzing SGBA also did not change substantially from 2009-2020, with grants examining sex differences or females increasing by 1.26% and 3.47% respectively, gender differences research funding decreasing by 0.49% and no change for 2S/LGBTQIA+-specific health. Our findings suggest more work needs to be done to increase researcher uptake in SGBA to advance health equity in research.HighlightsFunded grants focusing on sex or gender differences in health research have largely remained unchanged from 2009 to 2020 with the largest increase of 1.57% for sex differences research.Total funding amounts for sex or gender differences in health research have stagnated or declined across 2009 to 2020.Grants focusing on female-specific health did not change across 2009-2020, but the percentage of funding dollars increased by 3.47%.The percentage of grants focused on, and funding allocated to, 2S/LGBTQIA+-specific health more than tripled across 2009-2020 but remained less than 1% of all funded grants.

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