IEC 2025 | Bias in neuroscience research and the lack of research on sex differences in epilepsy

Yeah, it’s something that, you know, when I was preparing for that talk about cognitive and depressive or affective comorbidities in epilepsy, it was frustrating to see that, you know, you could not find the evidence. So it seems that, you know, there’s lots of research to be done about sex differences in epilepsy. But when I look into why we don’t know, I think it’s mainly because neuroscience, unfortunately, is biased. So there were a few interesting papers that described the sex biases in research. So that means when, you know, as studies include males and females, but they don’t disclose who’s male or who’s female for the purposes of understanding sex differences. And what they found is that in preclinical studies, so that’s in animal studies, the male-only studies outnumbered those with females 5.5 to 1. So that was a striking difference. And also when they looked at 10 different biological disciplines, they found that actually neuroscience was the most biased discipline of the 10 different biological sciences. So that was quite concerning, to be honest, because ultimately these biases, they can compromise our understanding of female biology in disease. And ultimately, you know, we cannot answer whether it’s actually cognitive or affective differences in people with epilepsy. And this is really important so that way we can target treatments that are tailored not only by the epilepsy type that the people have, but also it’s important to know whether it’s going to have a different effect in males, a different effect in females. So it’s something that we definitely need to address urgently. One of the, perhaps this is because there’s many misconceptions that prevent inclusion of females in epilepsy research. And some of them, I’ll just touch base on a few of them. One of them is that the animal numbers that researchers tend to think that you need to have more animals just if you include females. But this is something that is not entirely right because doubling up immediately when you start your work is not necessary, so potentially you can start with something that is a 50-50 ratio of males to females and then expand if the trend indicates so. It’s one of those misconceptions that have prevented the field from advancing, and also potentially the variability that can be introduced by the different estrous cycles in females. So again, it’s a misconception because the males also have a testosterone cycle. The females obviously have an estrous cycle. And also, latest research have indicated that there’s lots of influence of circadian rhythms. Even if you take, you know, one male, one female, you will notice different variability throughout the day. But that variability also, you can see it throughout the morning, throughout the year, so seasonal variability. So again, having that mindset that, you know, including females in research doesn’t impose more variability, that’s something that is not right. And I think overall that mentality that males go first, like why do we do that in research? It doesn’t make sense is that males go first. Like, I think this is just a flawed rationale, and it just unjustifiably prioritizes the use of males. It’s like, why do we have this archaic belief that males are the archetypal standard? This is just absolutely wrong. So it prevents us from actually investigating neurobiological potentially response effects of sex differences, but at the same time, just thinking that you know, you start with a project on males because, again, animal numbers, variability, cause whatever, it diminishes the scientific rigor. And that’s why it was really frustrating that I was not able to answer the question, do we have sex differences? Maybe in some cases, there are, but then we actually don’t know why those differences are. And ultimately, what that translates is that we are unable to offer tailored treatment for people with epilepsy. And it’s what I mentioned before, not only the epilepsy type, but also treatment that is personalized, whether you are a male, you are a female. So there’s lots of work that needs to be done to break those barriers of including females in epilepsy research.

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