It’s Not All Relative: Liberation from Gender-Bias in Neuroscience Research

Using the term ‘man’ to refer to ‘humanity’ may seem of little consequence to the day-to-day happenings of the world, but words reflect a reality more profound than letters on a page. They bleed into unquestioned standards, from social expectations to medical and scientific practice, with  unique implications of the latter for psychological research. This has been reflected most acutely in neuroscientific research. 

In neuroscience, it is standard practice to use animals for research, due to concerns regarding the ethics and feasibility of  conducting the same research on human test subjects, such as for drug testing. The goal within neuroscientific research is  generalizability – to have the results be comparable and directly applicable to humans. Ninety percent of the animals used in these studies are rodents, largely male rats and mice. There are several reasons why male rats and mice took priority, one of which is female mice having a more complex and variable hormonal profile, posing possible confounds in the research. This creates a hurdle in applying the results of such research to women, as there is a second layer of sex differences applied when generalizing from rodents to women, on top of generalizing from rodents to humans in general. Moreover, the reasons for preference of male rodents seem to be more of an unquestioned preconceived notion rather than a legitimate complexity in integrating female mice. Recent reviews show that there are ways to include them in rodent research while in no way increasing costs or making the research more complicated due to the hormonal profiles of female mice (Beery, 2018). 

This lack of research on female rodents compared to male specimens has already been shown to have profound effects in terms of gaps in research when assessing sex differences. For example, research on pain processing shows the dangers of using male mice as proxies to women. Allodynia is a type of nerve pain that makes all touch, from a simple brush of a finger to a legitimate touch, very painful. Research shows different biological markers in the genetic makeup of male mice and female mice with this disorder, as well as the markers associated with treatment effects (Sorge et al., 2015). This implies that what was previously considered a foolproof way in marking pain processing for all humans, seems to now be entirely inapplicable to the female population.

Another example comes from depression research. One of the treatments for depression is fluoxetine, which functions to increase serotonin levels in the brain. Research showed significant differences in the appropriate dosage of the drug for reducing depression-like symptoms in male and female mice, with a smaller dosage required for the latter (Hodes et al., 2010). Fluoxetine functions by enhancing cell proliferation, the process by which cells divide and contribute to tissue growth, which leads to an increase in serotonin levels. This is relevant as a growing body of evidence shows that depression may result in loss of gray matter volume in certain regions of the brain (Schmaal et al., 2016). The takeaway from the research was that, although the positive effects of fluoxetine in terms of  higher cell proliferation was seen in both male and female mice, the pattern of activation was varied among them, as well as the rate at which fluoxetine was metabolized by the mice. These are all very important factors to consider when deciding on the dosage of fluoxetine that is appropriate for human patients, as well as the expected effects of the drug. 

Finally, Alzheimer’s research is an area of particular importance when it comes to under-representation of female subjects, since women are a lot more likely to develop Alzheimer’s than men (Dye et al., 2012). Two hallmarks of Alzheimer’s in the brain are the presence of neurofibrillary tangles and amyloid plaques: both of these were significantly greater in number in the hippocampus in female mice over male mice. Despite this, only recently did research start implementing female mice as a standard for studying the disease.  Moreover, a difference was found in behavioral cognitive function between male and female mice, with female mice showing more impairment. Yet again, results such as this have tremendous implications for our understanding of the profile of Alzheimer’s.

The important thing to consider is that research guides theories, and theories guide a variety of our personal as well as professional understanding of how phenomena function, for example, mental disorders. It is not just the field of neuroscience that falls prey to these misrepresentations. For example, a review by Happé and Frithe (2020) has highlighted the major changes in our understanding of autism (ASD) throughout the decades of research into the mental disorder. Among one of the main misconceptions was the very high rates of misdiagnosis of ASD in women, due to a lot of the initial research being conducted on predominantly male samples. This misunderstanding of the condition in women could have been wholly avoided in light of a better integration and consideration of sex in research.

All of these examples are just a few of the many instances where research was not equally catered to women. Fortunately, there is some good news. Policies are starting to be implemented where there is a requirement for, for example, all preclinical studies on either humans or animals to have a balance of male and female subjects, where reasonably applicable (Clayton and Collins, 2014). It also helps that on a broader scale, we are able to understand that sex differences warrant active attention, in order to give anyone and everyone the right care and support that they deserve.